Penn Medicine News Blog Posts by Karen Kreeger

Karen Kreeger

Karen is responsible for disseminating information about the discoveries from the basic science departments within the School of Medicine, which includes cancer biology, cell & developmental biology, biological aspects of infectious diseases, neurosciences, pathology and laboratory medicine, and pharmacology, among other duties. Karen previously held this position in the late 1990s.

Karen has held positions in both public affairs and science and medical writing. She was senior editor at The Scientist, as well as maintained a freelance communications business for several years, writing for such clients as Nature, the Howard Hughes Medical Institute, the Journal of the National Cancer Institute, and the Wistar Institute.

Karen holds an MS in Scientific and Technical Communication from Oregon State University (1992) and an MS in Marine Studies from the University of Delaware (1985). She is also an author of a book on non-traditional careers in science.


View Karen's bio and beats

An Outdoor Kickoff to the Philadelphia Science Festival

Sci Fest logo outsideHead outdoors this weekend with Penn Medicine to kick off the fourth annual Philadelphia Science Festival.The weather for Saturday and Sunday is predicted to be 0% showers, with highs in the upper 60s and low 70s. Join Penn Medicine faculty, students, and staff at two of the city’s most spectacular venues for free, all-day events – Clark Park in West Philly and Smith Playground in Fairmount Park.

On Saturday, April 26, at 10:00 a.m. visit Discovery Day: Science in Clark Park. Discover science in your own back yard! Meet local scientists and students while exploring the natural wonders of one of the loveliest parks in the city. This year the Center for Brain Injury and Repair (CBIR) is again reaching out to many audiences with their message of how to mind your brain from concussions with such demos as eggs in Styrofoam to mimic a human head in a helmet. CBIR scientists will also be taking their brainy displays to students at after-school programs on April 28, 3:30 p.m. at the Haverford Avenue Library and April 29, 3:30 p.m. at the Charles Santore Library.

Then on Sunday, April 27, starting at noon, come to Explorer Sunday: Mess Fest, at the Smith Memorial Playground & Playhouse,3500 Reservoir Drive. The Franklin Institute brings the slimy and oozy MESS FEST to Philadelphia's favorite playground! Shoot off alka-seltzer rockets, make-and-take slime, and see how far the Soap Bubble monster will spread. While the kids are playing, learn about their brains, from toddling to teen in a talk with faculty from the Department of Neurology and others called What are They Thinking? How the Brain Develops from Infancy to Adolescence. Frances Jensen, MD, chair of Neurology, will talk about children and adolescents’ cognition, decision-making, coordination, and other developmental milestones. Mess Fest image

The Festival runs from April 25 – May 3, 10 days devoted to celebrating the region’s strengths in science and technology, bringing together more than 100 partners from academia to museums to restaurants. It will include an extensive line-up of programs and exhibitions designed to inspire the next generation of scientists and spark discussion among young and old. 

For more information on the full list of Penn Medicine participation in the science festival, visit the Penn Med News blog.

Using the Penn High Performance Computing Cluster to Unravel the Spider’s Web

Golden Silk Orb Weaver L Church Flickr Creative CommonsPenn Medicine Academic Computing Services was recently formed through the consolidation of several of the largest groups on campus providing computing services to departments, centers and institutes. Its role is to ensure that data, informatics, computing infrastructure, and technical expertise is readily available to grease the wheels of science and clinical care at Penn Medicine. We will occasionally bring you stories of their expanded role. I recently spoke with Brian Wells, associate vice president of Health Technology and Academic Computing and Ben Voight, assistant professor of Pharmacology and Genetics, about an unusual application.

Uncovering the genomic architecture of spider silk genes wasn’t top of mind for Benjamin Voight, PhD, when he first came to Penn a few years ago. But he and postdoctoral researcher Paul Babb are now deep into sequencing the whole genomes of two spider species: a Golden Silk Orb Weaver and Darwin's Bark Spider.

The de novo assembly of the whole genome of these two species is “like putting together a jigsaw puzzle without the box-lid picture to guide us.” says Voight, assistant professor of Pharmacology and Genetics. And a substantial amount of computing power is needed to do it, so Voight consulted with Brian Wells, associate vice president of Health Technology and Academic Computing, on the building and design of the new High Power Computing Cluster (HPCC) for this project.

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Penn Medicine at the 2014 Philadelphia Science Festival

PSF 2011 Carnival Dry icePenn Medicine will again play a starring role in the 4th annual Philadelphia Science Festival, a citywide collaboration showcasing science and technology every spring.

The Festival runs from April 25 – May 3, 10 days devoted to celebrating the region’s strengths in science and technology, bringing together more than 100 partners from academia to museums to restaurants. It will include an extensive line-up of programs and exhibitions designed to inspire the next generation of scientists and spark discussion among young and old. 

Take a look at who will be representing Penn Medicine at the 2014 Philadelphia Science Festival. Click on the links to each event to learn more. Watch this space for more about individual events and for coverage of the festival.

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Oxygen in our Bones

Vinogradov Nature imageEach day we take a breath about 20,000 times, bringing in oxygen that provides energy through a complicated reaction in the cell’s energy factory, the mitochondria. Just to break down one molecule of glucose – a basic reaction necessary for life -- into carbon dioxide and water takes six molecules of O2. On the other hand, a highly reactive form of oxygen called superoxide is created by immune cells from O2 to use against invading microbes. But, these reactive, charged oxygen molecules can be lethal to human tissues and are implicated in a host of diseases.

Sergei A. Vinogradov, PhD, associate professor of Biochemistry and Biophysics, at the Perelman School of Medicine, specializes in imaging of oxygen within the body using optical techniques.In 2008, his lab developed a new approach called two-photon phosphorescence lifetime microscopy (2PLM). This method allows him to look at oxygen distributions deep in tissue in three dimensions. The first applications of the method were in the brain.

Recently, working with many colleagues, the Penn team published in Nature the first application of 2PLM to directly quantify the physiological environment of blood stem cells, called haematopoietic stem cells, or HSCs. They asked: How can the marrow, which is highly permeated with blood capillaries, harbor blood stem cells in a low-oxygen microenvironment? Low oxygen levels in the HSC 'niche' keep stem cells in a quiescent state, protecting them against oxidative stress and maintaining their integrity until they are needed to make new cells, researchers surmise.

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Beyond the Ivory Tower: Penn’s Neuroscience Grad Students Reach Out During Brain Week, and Beyond

NGG KidsJudge 2013 Synpatic LandPhiladelphia is a cerebral city this spring. To start, every March, Brain Awareness Week brings together institutions worldwide to celebrate the brain. Activities include open days at neuroscience labs, exhibitions about the brain, and displays at libraries, community centers, and science museums.

The Neuroscience Graduate Group (NGG) at the Perelman School of Medicine held its first annual Penn Neuroscience Public Lecture for Brain Awareness Week to a packed auditorium. The four TED-style talks covered how diet affects the brain, how people make choices about abandoning long-term goals, heritable memory problems from cocaine-abusing fathers, and bionic-like axon growth for nerve repair.

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Transcription Factors Key to Using T Cells Against Cancer, Chronic Infection

Wherry BATF spiral blog post Mar 14Business is brisk in the lab of John Wherry and his team from the Department of Microbiology and the Institute for Immunology for papers on killer and helper T cells. Two studies -- bound by their focus on transcription factors important in the immune response – have come out of the lab in the last few weeks. And, they both identify potential new targets for cancer immunotherapies.

Transcription factors are proteins that attach to specific DNA sequences in the nucleus to control availability of DNA to be transcribed into messenger RNA. These factors control the differentiation of killer T cells -- whose job is to eliminate infected cells or tumor cells, as well as the support crew helper T cells. This type of T cell coordinates other arms of the immune response including sustaining killer T cells and aiding B cells in making antibodies. 

The lab’s paper in Immunity “was a genomic-scale profiling of what prevents T cells from responding to persisting infections or cancers,” says Wherry. The main players in the profile are sets of surface proteins on helper and killer T cells that prevent them from recognizing tumor or infected cells as “other.” Collectively, these proteins are called checkpoints in the immune response, and the team found that certain transcription factors play a larger role than first expected in the intricacies of the immune response.  

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A Rare-fied Friday at the End of Every February

MDBR-Graphic with Penn logo Final FinalRare Disease Day is an annual world-wide event to raise awareness with the general public and decision-makers about rare diseases and their impact on patients’ lives. Here in Philly, join the Penn Center for Orphan Disease Research and Therapy at the World Café Live from 5-7 Friday the 28th for the kickoff celebration of the Million Dollar Bike Ride for rare disease, the Center's own annual grass-roots event. Network with cyclists, learn from orphan disease researchers, and meet families with a direct connection to these efforts.

Orphan/rare diseases represent a collection of disorders that affect fewer than 200,000 individuals for any single disease type, yet there are more than 7,000 distinct orphan diseases. In all, over 25 million people in the United States are afflicted by orphan diseases. Most rare diseases are genetic and present throughout the person's life, even if symptoms do not immediately appear. Many rare diseases do appear early in life, and about 30 percent of children with rare diseases will die before reaching their fifth birthday. Despite this huge number, research on most diseases in this group has lagged far behind other major areas due to a combination of technological and funding limitations.

Even though the Rare Disease Day campaign started in Europe, it has progressively spread across the world, with over 70 countries participating in 2013. The hope of the movement is for the World Health Organization to recognize the last day of February as the official Rare Disease Day. 

And Penn Medicine is doing its part. The ongoing work at Penn on rare diseases runs the gamut from basic biology to clinical testing. Nearly a third of the projects are in the preclinical stage, with scientists working to uncover molecular and cellular causes for these disorders, which together reach every system in the body. Penn researchers are conducting nearly 300 different projects on 129 rare and orphan diseases.

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Where Do We Go From Here? Public Health and Unconventional Natural Gas Drilling

CEET Symposium flyer Feb 14Last week the Center of Excellence in Environmental Toxicology (CEET) and the Center for Public Health Initiatives (CPHI) at the University of Pennsylvania co-hosted a symposium on the public health effects of natural gas drilling operations. Their aim was to profile the state of the science in this contentious field. Stakeholders from four major affected groups – government, academia, industry, and concerned citizens participated as speakers and attendees.

It was Aubrey Miller, MD, MPH, senior medical advisor to the National Institute of Environmental Health Sciences (CEET’s funder), in the last session of the day, “Where Do We Go From Here?,” who put the goal of the symposium into perspective for me: A PubMed search he ran on hydraulic fracturing came up with only a small handful of papers regarding the health effects or exposure information in this database of peer-reviewed literature, even though there are reportedly more than 52,000 wells in the US, with as many as 15 million Americans living within one mile of hydraulic fracturing activities.

“Our hope is that respectful discussion on this broad range of issues will provide participants with information to embrace evidence-based decision making,” wrote CEET director Trevor Penning, PhD, and CPHI director Jennifer Pinto-Martin, PhD, MPH in their welcome to attendees, addressing this imbalance of information versus the ubiquity of this relatively new energy-extraction process.

Hydraulic fracturing, colloquially known as fracking, is a process that forcibly injects a mixture of fluids into shale formations deep below the earth’s surface. This process fractures -- technically, creates a fissure within -- the rock in order to release natural gas and oil trapped inside. In Pennsylvania, this non-renewable resource is part of a large geological formational called the Marcellus Shale, with roughly half of the state lying above the formation.

For many at the meeting, unconventional natural gas drilling operations seemed to come “out of nowhere” about five years ago within the Commonwealth. Still, the answer to the question of the potential public health and environmental effects of hydraulic fracturing on air and water quality remains unclear.

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Celebrating a Lifetime of Dual Career Success

Armstrongs Clay ClaraPenn has its share of science luminaries, many in the same household, and at all stages of career path. Perelman School of Medicine long-time physiologists Clara Franzini-Armstrong, PhD, Emeritus Professor of Cell and Developmental Biology, and Clay Armstrong, MD, Emeritus Professor of Physiology, are both members of the National Academy of Sciences and the only married couple to hold that honor. That’s just where their list of contributions to science begins.

Armstrong won the Laskar Award for Basic Science in 1999, the John Scott Award in 2000, and the Gairdner Foundation International Award in 2001. Franzini-Armstrong won the 1989 K.C. Cole and the 2007 Founder's Awards from the Biophysical Society and received an honorary MD from the University of Pisa in 1997. She is also a member of the European Academy of Sciences and a foreign member of the Royal Society London.

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Cancer in Waiting: Latency in Viral-Based Cancer Explained

LANA pathwayThe lab of Erle Robertson, PhD, professor of Microbiology, and program leader of Tumor Virology at Penn’s Abramson Cancer Center, has been studying how Kaposi’s Sarcoma-associated Herpes Virus (KSHV) subverts normal cell machinery to cause cancer for more than a decade.

Kaposi’s sarcoma is a type of cancer caused by an associated herpesvirus. In the US, it usually occurs in people with a weak immune system caused by AIDS or in other immune-compromised individuals, and before the AIDS epidemic, Kaposi sarcoma was considered rare. At that time, about two new cases were found for every million people each year, according to the National Cancer Institute. With the AIDS epidemic, the incidence of the sarcoma in the US increased by 20 times, peaking at about 47 cases per million people (per year) in the early 1990s. Now, with new treatments for AIDS, the sarcoma occurrence is about six cases per million people each year, according to the American Cancer Society.

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Could Statins be Used to Fight a Deadly Viral Infection?

Hanta entry path Hannah Barbian

To celebrate February as American Heart Month, the News Blog is highlighting some of the latest heart-centric news and stories from all areas of Penn Medicine.

Two Perelman School of Medicine microbiologists may have found a way to use statins, the well-known blockbuster cholesterol-lowering drugs, to fight the hantavirus, a mysterious and lethal microorganism that appeared suddenly in the US southwest over 20 years ago. That first outbreak led to the deaths of more than a dozen people, most of them in their prime. The last reported outbreak happened in Yellowstone Park in 2012.

Only about 30 known human cases of hantavirus are reported in the US each year. The respiratory syndrome caused by a hantavirus infection comes from breathing in small viral particles in the excrement of infected rodents. It starts out with flu-like symptoms that quickly deteriorate into a dangerous form of adult respiratory distress syndrome. It is among the most deadly known human viruses: 30 percent to 40 percent of people who are diagnosed die from hantavirus pulmonary fever.

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The “Other”Circulatory System

Kahn JCI image graphic Jan 14Blood is the life force of animals. But behind the more well-known system of veins, arteries, and capillaries functions the mop-up crew, the  vascular network called the lymph system.

Mammals transport blood through a high-pressure, closed vascular network while lymph, composed primarily of interstitial fluid and immune cells, is transported in an open, low-pressure system. The lymphatic system is one-way, starting at the capillaries where the connections between endothelial cells are loose to allow easy entry into the system. Fluid, cells, and proteins accumulate in the interstitial spaces among the tiniest of blood vessels where a small pressure gradient builds up, allowing lymph to passively and slowly flow into lymphatic vessels.

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Renaissance Biochemist

Dutton head shot sketch Nov 13Les Dutton, Ph.D., will be awarded the 2013 John Scott Award next week. He will be honored with a medal, certificate, and $12,000 for his "work on the elementary processes of oxidation-reduction and the diverse biological events coupled to it." Dutton is the Eldridge Reeves Johnson Professor of Biochemistry and Biophysics, the director of the Johnson Foundation for Molecular Biophysics, a Fellow of the Royal Society, and former chair of the Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania. And an accomplished artist, but more on that later.

The work for which Dutton is cited for the Scott Award - "the elementary processes of oxidation-reduction and the diverse biological events coupled to it” – is an understatement.

“Bottom line – over the years, we have described how quantum mechanics is translated to basic biology via natural selection,” he says. “Every time we breathe, bringing oxygen into our bodies, we activate electron tunneling, which ultimately makes biochemical energy in the form of the molecule ATP. In a way, to put this fundamental knowledge into stark perspective, when humans die, we ultimately die of power failure.”

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Finding Antitumor T cells in a Patient’s Own Cancer for Personalized Therapy

Powell Clinical Cancer Research schematic Nov 13Patients with tumors that contain increased numbers of T lymphocytes generally survive longer than those with tumors without T-cell involvement, suggesting that T cells with potent antitumor function naturally exist in cancer and control tumor progression. With the exception of melanoma, it has been difficult to identify and isolate the tumor-reactive T cells from common cancers, however, the ability to do so could be used to fight a patient’s own cancer.

In a paper recently published in Clinical Cancer Research, investigators in the lab of Daniel Powell, PhD, at the Perelman School of Medicine, University of Pennsylvania, demonstrated for the first time that a T cell activation molecule can be used as a biomarker to identify rare antitumor T cells in human cancers. The molecule, CD137, is a protein that is not normally found on the surface of resting T cells but its expression is induced when the T cell is activated.

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Postdocs Building Community, and Experience

Postdoc Symposium poster session Nov 13According to a recent article in Genetic Engineering and Biotech News, the perennial topic of the overabundance of postdocs and PhDs, is “getting some overdue additional attention” from upcoming studies on the topic.

One such study is by a National Academies’ Committee on Science, Engineering, and Public Policy panel, who is updating the 2000 report Enhancing the Postdoctoral Experience for Scientists and Engineers. It will be interesting to see their recommendations on how well U.S. postdoc programs meet the needs of scientists and broader research activities, and how the postdoc landscape has changed over the last two decades. For example, a 1997 report from the Commission on Professionals in Science and Technology, Postdocs and Career Prospects: A Status Report, found that, overall, of those in postdocs in 1993, 13 percent were in tenure-track positions two years later, and for those in their second or third postdocs in the same year, 16 percent were in tenure-track positions by 1995.

Clearly, interest in career issues for postdocs is not new, but ways to expand the postdoc experience to ready for budding careers takes constant creativity and communication.

To that end, the Biomedical Postdoctoral Council (BPC) at the Perelman School of Medicine, University of Pennsylvania, held its 12th annual Postdoctoral Research Symposium last week. BPC is one of the first grassroots postdoc organizations in the US, and 700 out of its 800 members work in Penn Medicine departments.

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Cancer Hitchhikers

Simon Cancer Discovery image cancer hitchhiker no label Oct 13 take 2This image of an extracellular matrix – in this case collagen (blue) plus tumor cells (red cells attached to blue fibers, arrow) from a human sarcoma -- shows the mini highway along which tumor cells migrate toward blood vessels in order to metastasize (left panel). The way in which tumor cells use collagen to hitch a ride is still a mystery. Penn Medicine researchers, using a sophisticated laser-based technology called multi-photon second harmonic generation imaging to take pictures of tumor tissue expressing green florescent protein, were able to see tumor cells and collagen in action. The right panel shows a cross section of more normal collagen without tumor cells and with red blood cells populating the opening of the vessel.

With this zoomed-in view, the Abramson Family Cancer Research Institute (AFCRI) lab of Celeste Simon, PhD, and postdoctoral fellow, T.S. Karin Eisinger-Mathason PhD, report in Cancer Discovery about the potential of the collagen-modifying enzyme PLOD2 as a new therapeutic target for the treatment of metastatic undifferentiated pleomorphic sarcoma (UPS). Simon is the AFCRI Scientific Director, an Investigator with the Howard Hughes Medical Institute, and a professor of Cell and Developmental Biology.

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Hanging Cancer on the Fulcrum of the Acidic Hinge

Roth Cell Reports Acidic Hinge blog post image genomic instability Sept 13Peter Nowell, David Hungerford, and Janet Rowley are famous for their contributions to understanding how translocations -- swaps of genetic bits between chromosomes – are the genomic basis for some blood cancers. This story of the Philadelphia Chromosome is now legendary.

Other blood cancers are also related to mutations that can cause translocations, for example ones in V(D)J recombinase, an enzyme responsible for cutting and pasting DNA to generate a diverse repertoire of antigen receptors for immune cells. This research also started decades ago, in the 1980s, by Phil Leder, Carlo Croce, and others, with the observation that certain B-cell lymphomas contain cancer-causing translocations that apparently result from errors in V(D)J recombination.

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Developing Nematode Worm Star of Award-winning Video

 

Who knew that nematode worms could hold their own in minutes-long videos? John I. Murray, PhD, assistant professor of Genetics at the Perelman School of Medicine at the University of Pennsylvania, and postdoc Amanda L. Zacharias, PhD, produced one of the two award-winning videos in the recent Federation of American Societies for Experimental Biology (FASEB) second annual BioArt competition. Zacharias is working on identifying the targets of Wnt signaling, an important molecular regulator of embryonic development, using the worm as her model organism.

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The Med Days of Summer

PARS 1The end of summer comes in many forms, from the day after Labor Day weekend to the eve of the autumnal equinox. On the Penn Med campus, mid-August marks the start of the end for many undergrads and high-school students who are wrapping up lab experiments and making presentations about their work in an array of programs designed to showcase what research is all about.

The day I visited the Penn Academy for Reproductive Sciences (PARS) last week, Monica Mainigi, MD, assistant professor of Obstetrics and Gynecology, and research specialist Teri Ord were showing students from area high schools what mouse sperm and eggs look like. The PARS program is a research clinic for high-school girls that focuses on the science behind human reproduction and careers in research and clinical medicine.

PARS runs three times a year, with a three-day session in the summer for up to 15 young women. It's funded by the National Institutes of Health and is a joint effort by the Department of Cell and Developmental Biology, Penn Fertility Care, the Center for Research on Reproduction and Women's Health, and the Institute for Regenerative Medicine.

The students get to see hands-on labs, and the day I attended was devoted to in vitro fertilization. The students mixed mouse eggs and sperm and saw that the many wiggling sperm that outnumber and attach to one egg are so plentiful that the eggs literally spin on the microscope slides. These vivid lab demonstrations lent themselves to impromptu talks about the ethics and reasons for egg freezing and IVF, as well as teen birth control.

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Cycling for Cancer and Zebrafish

James Dutko, PhD, a postdoctoral researcher at the Perelman School of Medicine 's Department of Cell and Developmental Biology, spent a hot Sunday morning earlier this month cycling in the 41st annual Philadelphia Bike-a-Thon, an annual fundraising event for the American Cancer Society (ACS).  Dutko after race Blog image July 13

“This year the event brought in 1.1 million dollars to the ACS and its mission to overcome the disease of cancer,” says Dutko. “The Philadelphia bike-a-thon is well organized and accessible to anyone who enjoys riding a bike.” Dutko, pictured here with his wife, rode 65 miles, one of seven distance options, and was supported by family and friends with their donations to the ACS.

Dutko rides his bike everyday to the lab, a time when he does some creative thinking about science. Back when he was working toward his doctorate at the SUNY, Albany, he raced with the Capital Bicycle Racing Club in upstate New York.  Dutko’s ACS fellowship brought him in contact with the organizers of the Philadelphia bike‑a-thon, which he found to be an ideal way to contribute to the fundraising efforts of the ACS.

His ACS research fellowship in the lab of Mary Mullins, PhD, professor of Cell and Developmental Biology, allows him to study characteristics of the bone morphogenetic protein (BMP) signaling pathway and how it contributes to the disease of cancer. He investigates how the pathway normally works in the zebrafish, a seemingly odd model for human cancer studies.

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Opening Science Career Doors Early On

Kareema Dixon May 2013As a ninth grader at Northern Liberties’ Bodine High School for International Affairs, Kareema Dixon took part in the BioEYES program developed by Jamie Shuda, EdD, Director of Life Science Outreach at the Institute for Regenerative Medicine (IRM), Perelman School of Medicine, University of Pennsylvania. Little did she know that this one course would send her on an amazing educational path. And she only just finished tenth grade last month. BioEYES is a K-12 science education program that provides classroom-based learning using live zebrafish.

Dixon’s science teacher Maggie Pedone, who brought the BioEYES program to her ninth grade class, also encouraged Kareema to start entering area science fairs. Fittingly, Dixon chose for her first science fair a project based on zebrafish. Her project, “Does Oil Make You Boil: The Truth behind Oil Spills?” uses zebrafish to measure the phototoxicty of oil. She worked after school with Penn undergrad mentor Mounica Gummadi through the IRM’s Bridge to ReBIO program. Bridge to ReBIO is an after-school and weekend program where Penn STEM (science, technology, engineering, math) majors mentor local high school students in developing relevant, sound science fair projects.

How did she become interested in environmental science? From a school presentation on the Gulf oil spill during the BioEYES program. “It was really disturbing to see what happens to zebrafish embryos first-hand when exposed to oil,” says Dixon. “It’s really better to do science hands on.”

She ended up winning the George Washington Carver science fair, taking first place in her category of environmental science. She also won prizes from the Environmental Protection Agency and the Cobbs Creek Environmental Center for her project, and placed third place in the Delaware Valley Science Fair later that year in ninth grade.

Not willing to rest on her laurels, Dixon made this promise to herself and her mentors: “I’m doing this next year and will place first.”

Her participation also paid off in opportunities over last summer – she worked as a park manager at Cobbs Creek, where she presented her water quality testing skills many times.

In tenth grade, Dixon has been working with Albert JinHyung Ahn, another Penn undergrad mentor on what’s “Really Left Behind? An Experimental Study of Oil and Dispersant Toxicity,” another environmental study using zebra fish.

In March, Dixon took first place in her category of environmental science again at the Carver Science Fair. She also won the EPA prize again, as well as a Naval science prize.

Making good on her promise, she also placed first in the Del Val Fair in early April, for the environmental science category.

“She did it!” exclaimed Shuda.

Her work was also entered into the Stockholm Junior Water Prize, part of the Water Federation.  She wrote a paper about her research and is in competition for a trip to Oregon if she places first in Pennsylvania.

And just to keep things balanced, Dixon also participates in Students Run Philly Style, where she completed the Broad Street Run. She is also on the debate team, describing herself as “competitive,” she says with a grin. This summer, she will participate in the University of Delaware's Edge honors program, where she will live on campus and take college courses.

The adults in her life are full of praise for her achievements: Shuda says she only gives her a little mentoring and “then she is off and running. She is a true example of how with a little mentoring, students can do great research.”

Find out more about the IRM’s educational outreach opportunities.

Tweaking T Cells for Transplants

Hancock Blood blog post image May 13Bone marrow transplants, like the high-profile match between the son of heavyweight fighter Evander Holyfield and 19-year-old Nashville native Darian Craig, profiled in People magazine earlier this month, run the risk of graft-versus-host disease (GVHD), a life-threatening complication where the donor cells attack the patient’s own cells.

BMT procedures replace damaged or destroyed bone marrow with healthy bone marrow stem cells. The marrow is the soft tissue at the heart of bones where immature cells that give rise to all blood cells – which include immune cells - are made. During the repopulation of the immune cells after a BMT, different populations of T cells mature quicker compared to others, and this difference contributes to attack by the newly reconstituting immune cells on the body in GVHD.

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2013 Philadelphia Science Festival Recap

PSF 2013 Carnival Penn tent village 1Now that the school year and the focus on formal science education is slowing down, these images of Penn Medicine faculty, staff, and students sharing their love and knowledge of biomedical science with members of the public from infants to senior citizens during the 2013 Philadephia Science Festival may spark inspiration to last all year. Penn Med took part in a dozen activities all over the city, from a Carnival on the Ben Franklin Parkway that reached over 25,000 people to a TED-talk style panel discussion on innovation and funding at the historic Iron Gate Theatre. See ya' in 2014! 

Tau is its Own Worst Enemy

Cohen Nature Struct Mol Bio Blog post schematic Apr 13Two years ago, Penn neurodegenerative researchers determined that a well-known chemical process called acetylation has a previously unrecognized association with one of the biological processes associated with Alzheimer’s disease and related disorders. The findings were published in Nature Communications by first author postdoctoral fellow Todd Cohen, PhD, and senior author Virginia M.-Y. Lee, PhD, director of Penn’s Center for Neurodegenerative Disease Research.

Tau is one of the primary disease proteins associated with neurodegenerative diseases. Tau proteins are expressed primarily in the central nervous system where they help with the assembly and stability of microtubules, protein structures that are the backbone of nerve-cell axons.  

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Science Communications, One White-Board Video at a Time

FitzGerald Nat Med mouse side by side image Nov 12Science comes to life in countless ways -- in hundreds of booths on the Ben Franklin Parkway and dozens of cafes during the Philadelphia Science Festival, in children's books like the "Magic Schoolbus" series, but sometimes it's the simplest tools that provoke an aha moment.  

In an online video series, Florie Charles, a doctoral student at the University of California at San Francisco, and founder of Youreka Science, simply uses a white board and colored markers (and occasionally a small cut out mouse -- animal, not computer peripheral) to explain findings from recent papers in an accessible, fresh, and engaging way. One of her newest videos happens to feature a recent publication from the lab of Garret FitzGerald, MD, FRS, director of Penn Medicine's Institute of Translational Medicine and Therapeutics.

 

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Celebrating the Work of Medical Laboratory Professionals

Lab Week 2013 Poster WinnerMore than 10 billion lab tests are performed every year by more than 300,000 medical laboratory professionals across the United States. At Penn Medicine, close to 1,200 faculty and staff in the department of Pathology and Laboratory Medicine work around the clock to perform critical patient care functions such as running blood banks and conducting tests that provide essential data to make diagnoses of all kinds and keep patients safe throughout their hospital stays.

Laboratory professionals are among the unsung heroes of patient care as the team behind the scenes who "get results" or prepare lifesaving therapeutic products, ranging from donated immune cells for infusing into cancer patients undergoing bone marrow transplants to blood for resuscitating patients who've had traumatic accidents.

Increasingly, technology allows patients a glimpse of this important work, by delivering real-time results that help physicians select and manage therapies. But much of this work still remains out of sight from hospital wards and outpatient clinics. Most patients and caregivers will never meet these lab professionals in person, although many decisions for primary and specialized care depend on the expertise and advice from clinical labs in some way.

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Center for Brain Injury and Repair Presence at Philadelphia Science Festival Reaches Science Enthusiasts of all Ages

PSF 2013 Carnival Brain Tent 1 croppedThe Philadelphia Science Festival, from April 19 – 28 this week, celebrates the region’s strengths in science and technology, bringing together more than 100 partners from academia to museums to restaurants.The Festival will include an extensive line-up of programs and exhibitions designed to inspire the next generation of scientists and spark discussion among young and old. 

This year the Center for Brain Injury and Repair (CBIR) is reaching audiences of all stripes with their message of how to mind your brain from concussions with such demos as eggs in Styrofoam to mimic a human head in a helmet.

On Saturday, April 20 CBIR was part of the “Penn village” at the Science Carnival on Ben Franklin Parkway. They and many other Penn groups of exhibitors shared their knowledge and enthusiasm of science and technology:

  • Laboratory for the Research of the Structure of Matter
  • Netter Center for Community Partnerships
  • School of Veterinary Medicine
  • Upward Bound Math and Science 
  • Biomedical Graduate Studies
  • GRASP Lab

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Truckin’ Molecular Motors: The Tilt and Wobble of Myosin-V

Goldman Biophysical Journal cover Mar 13Never in a million years would I have thought that I’d be writing about blues musician Blind Boy Fuller, cartoonist R. Crumb, and molecular motors in the same blog post. The Popular Science blog and sci-fi future blog io9 took notice first. The cover of last month’s Biophysical Journal likens movement of the molecular motor Myosin-V to the exaggerated, wobbly gait of R. Crumb’s “Mr. Natural” on the cover of Blind Boy Fuller's record album "Truckin' My Blues Away."

There’s even a link to a 1930s Fuller recording on the io9 post. The Pop-Sci post has a great 22 second animation of a kinesin molecule “walking” along a microtubule while dragging its large cargo and another video of Myosin-V’s tilt and wobble on an actin filament.

These all refer to papers recently published by researchers from the Pennsylvania Muscle Institute. The Biophysical Journal cover is an adaption by sci-artist Patrick Lane submitted by Penn scientists.

The labs of senior authors Yale E. Goldman, and Erika L.F. Holzbaur, both in the Physiology department, have been studying molecular motors for close to a combined five decades. Colleagues Henry Shuman, Phillip C. Nelson in Physics, Haim Bau in Mechanical Engineering, Russel J. Composto in Materials Science, and PMI director Mike Ostap round out the team.

They investigate molecular motors -- proteins that function as tiny molecular machines to move cargos within a cell – to get a better handle on what happens when the transport of cellular cargo goes off track and how that may be the start of developmental and neurodegenerative diseases.  

The Biophysical Journal paper details how Myosin-V works in the “harsh” environment of the cell on a nano scale. Myosin-V must function in a sea of water molecules that bombard it 1012 times every second. And what’s most spectacular is that myosin uses this seemingly chaotic environment to adjust its short-lived sub-steps to search for the next binding site on its actin track to keep efficiently moving onward. Literally, myosin V uses its fluctuating environment to extend its reach to take each new step.

 

Goldman, Nelson, and company conduct their observations into this micro world with single purified molecules using custom a fluorescence microscope that Goldman and junior colleagues designed and built to see the detailed tilts and wobbles of molecular motors. He calls this the “bottom up” approach.

The researchers also use super-high resolution cell bioimaging, the “top-down approach.” A related paper recently published in the Proceedings of the National Academy of Sciences uses both approaches to understand how components of cell motility like the cytoskeleton and molecular motors work together. Using optical trapping technology in live cells, they found that different types of molecular motors work as a team to get to their target destination. In the center of cell, dynein and kinesin work on microtubule tracks and switch to myosin on actin tracks at the periphery of the cell. Using immune cells called macrophages, they asked, how the microtubule motors operate together. They found that cargoes simultaneously engage with many microtubules and generate high forces to move back and forth in the macrophages.

These papers illustrate how scientific collaborations across multiple disciplines coupled with development of new biophysical technology facilitate discriminating measurements on complex biological networks, notes Goldman. Both of the papers, he adds, show that molecular motors have also evolved sophisticated collaborative adaptations to conduct their essential transport functions. 

 

Penn to Celebrate Big Ideas in Science at the 3rd Annual Philadelphia Science Festival

PSF logo 2013Penn’s signature event at the 3rd annual Philadelphia Science Festival next week is a sure sign of the times. “Big Ideas: Funding and Innovation” draws on current themes and reminders of where the bright ideas really come from. Fundamental research at such government agencies as the National Institutes of Health and the National Science Foundation spur today’s most successful businesses and healthcare innovations. Federal funds from taxpayer dollars drive the development of nearly all of the top technologies that permeate our lives.

 

On Tuesday, April 23, 2013 at 6:30pm at the historic Iron Gate Theater, 3700 Chestnut Street, NSF Director and 2013 Franklin Medal awardee Subra Suresh will open a discussion on the importance of federally funded research at laboratories in research universities.

 

Iron Gate TheatreIn TED-talk style, a group of Penn and Drexel innovators will share their real-life examples of how federal funds have contributed to their Big Ideas:

Garret FitzGerald, MD, FRS, Chair of the Department of Pharmacology, and Director, Institute for Translational Medicine & Therapeutics, Perelman School of Medicine, studies how drugs work in the body. His lab leads the way, with many firsts, to help people lead healthier lives -- discovering how low-dose aspirin is important for heart health, showing which anti-inflammatory drugs might be harmful, and finding an internal body clock important to the circulatory system and when best to take medications.

Chris Hunter, PhD, Chair of the Penn Vet Department of Pathobiology, uncovers ways in which certain proteins cause or prevent inflammatory diseases to create more accurate models of immune-system function, to combat diseases from cancer and arthritis to HIV/AIDS.

Adam Fontecchio, PhD, Professor of Electrical and Computer Engineering and the Associate Dean of Undergraduate Affairs in the College of Engineering, co-directs Drexel’s Expressive and Creative Interaction Technologies (ExCITe) Center, a hub for enabling teams of faculty, students, and entrepreneurs to pursue multi-disciplinary collaborative projects. He investigates liquid crystal interactions to develop novel devices.

Jordan Miller, post-doctoral fellow in the Tissue Microfabrication Laboratory in the School of Engineering and Applied Sciences, combines chemistry and rapid prototyping to direct cultured human cells to form complex organizations of living vessels and tissues. He is one of the founding members of the 3D maker community, using 3D printing in his regenerative medicine research.

Tickets can be purchased here and the full calendar of PSF programs is available here.

Penn Med at the 2013 Philadelphia Science Festival

PSF logo 2013Penn Medicine will play a starring role in the Philadelphia Science Festival again this year. The Festival is a citywide collaboration showcasing science and technology every April. 

This year it runs from April 19 - 28, 10 days to celebrate the region’s strengths in science and technology, bringing together more than 100 partners from academia to museums to restaurants. The Festival will include an extensive line-up of programs and exhibitions designed to inspire the next generation of scientists and spark discussion among young and old. 

Take a look at who will be representing Penn Med at the 2013 Philadelphia Science Festival. Penn Med participants are in bold. Click on the links to each event to learn more. Watch this space for more about individual events and for coverage of the festival.

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Defining the Traits of Transmitted HIV-1 to Make Better Vaccines

HIV Red Ribbon by Trygve.u Mar 13

Know the traits of HIV-1 strains capable of establishing new infections could be important for AIDS vaccine development.

After developing methods for their accurate identification, George Shaw, Beatrice Hahn, and Nicholas Parrish, from the Department of Microbiology at the Perelman School of Medicine, and their colleagues, generated infectious clones of transmitted founder and chronic control HIV-1 strains and compared their traits to probe the earliest stages of HIV-1 infection.

Transmitted founder (TF) viruses from acutely infected patients have all the genetic tools to start a new infection, while chronic control (CC) viruses from long-term HIV patients have the genetic tools to sustain an infection for years.

After a transmitted founder strain of HIV-1 infects mucosal tissues, it spreads to nearby and distant tissues, including the gut-associated lymphoid tissue. There, the virus expands exponentially, triggering a systemic cytokine storm, preceding peak viral load in the blood.

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Spring Fever at the 2013 Philadelphia Science Festival

PSF logoThe Philadelphia Science Festival is a little over a month away. So many activities to choose from in this now annual spring extravaganza of science, technology, and engineering. Penn Medicine will again participate in many events, and this year's theme is Be Curious! The new Festival video says it all. The events calendar is starting to fill out, so take a look at the new 2013 Festival site.

 

The Penn Center for Brain Injury and Repair will again participate in Science Day at the Ball Park. At the Mind Your Brain table you will be able to learn how your brain works and how to take simple preventive steps -- like wearing a helmet during any contact sport -- to "mind your brain." Families can view nerve cells under a microscope and find out how Silly Putty mimics your axons.

The Phillies are teaming up with the Festival for the third straight year, with a focus on the science of baseball. Held during the Thursday, April 25 Citizens Bank Business Persons Special game against the Pittsburgh Pirates, children can explore and take part in fun science activities throughout the concourse and complete tasks at each location to earn stamps on their own Citizens Bank Park map. If you earn five stamps or more you can receive a Science Day Water Bottle!

Classrooms are encouraged to attend the game that day and teachers can receive pre- and post-Science Day curriculum.

Tickets are on sale and at a $6 discount for tickets under $30 at the Science Day site. All purchasers just need to type in SCIENCE under the special code to apply the discount. April 25 also happens to be Take Your Child to Work Day so families are also welcome.

Watch this space for more information about other Philadelphia Science Festival events!

Heart Research Hits Close to Home for a New Penn Med Prof

Voight Ben desk shot Jan 13To celebrate February as American Heart Month, the News Blog is highlighting some of the latest heart-centric news and stories from all areas of Penn Medicine.

“I know this sounds like a cliché, but one of the main reasons I’m interested in learning about the genetic basis of heart disease is because my father’s side of the family has a terrible cardiovascular profile. If anyone understands the urgent need to identify novel targets for therapy, I certainly rank high on the list.” says Benjamin F. Voight, PhD, assistant professor of Pharmacology and Genetics at the Perelman School of Medicine, University of Pennsylvania. Voight’s father, a Major in the Air Force and a fighter pilot, passed away in his late 50s. He had his first heart attack in his late 30s, and as a result, suffered with vascular dementia, a decline in cognitive skills caused by blocked blood flow to the brain, depriving brain cells of oxygen and nutrients.

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The Many Faces of Metformin

Metformin blog post goat's rue Jan 13

In 2004, Clifford Bailey of the Diabetes Group from Aston University in Birmingham, United Kingdom described metformin, the most widely prescribed drug for treating diabetes, as ironic: In our high-tech era of drug discovery and development this first-line treatment for type 2 diabetes is little removed from an herbal remedy of the Middle Ages. Despite its chemical simplicity and detailed investigation, metformin continues to evade a complete exposé of its cellular activity (Pract Diab Int April 2004 Vol.21 No. 3)

Now, almost a decade later, a team led by Morris Birnbaum, M.D., Ph.D. from the Institute for Diabetes, Obesity and Metabolism, is getting closer to a clear picture of how this drug works, which, in addition to its widespread use for diabetes, is being tested for treating dementia and cancer.  

The Birnbaum lab and colleagues found that metformin works in a different way than previously understood. They found that in mice it suppresses the liver hormone glucagon’s ability to generate an important signaling molecule, which points to new drug targets.

For fifty years, one of the few classes of therapeutics effective in reducing the overactive glucose production associated with diabetes has been the biguanides, which includes metformin. The inability of insulin to keep liver glucose output in check is a major factor in the high blood sugar of type 2 diabetes and other diseases of insulin resistance.

“Overall, metformin lowers blood glucose by decreasing liver production of glucose,” says Birnbaum. “But we didn’t really know how the drug accomplished that.”

Birnbaum’s Nature study describes a novel mechanism by which metformin antagonizes the action of glucagon, thus reducing fasting glucose levels. The team showed that metformin leads to the accumulation of the protein AMP in mice, which inhibits an enzyme called adenylate cyclase, thereby reducing levels of key enzymes and eventually blocking glucagon-dependent glucose output from liver cells.

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When Art Meets Science

Guo Dreyfuss Cell snRNP cover 2012Frank Oppenheimer, founder of the famed science museum in San Francisco, the Exploratorium, called artists and scientists “the official ‘noticers’ of society,” adding that “they notice things that other people either have never learned to see or have learned to ignore, and communicate those ‘noticings’ to others.”

Lili Guo, a PhD student in the lab of Xiaolu Yang, PhD, in the Department of Cancer Biology and Abramson Family Cancer Research Institute, is most definitely an official “noticier.”  

Art is in her genes. So is science.

She comes from a family of artists. Her father is a professor of lithography and her mother is a graphic designer for a major publisher, both in China. She has been doing art in many forms since she was five and has been trained in many classical forms: “It has been part of my daily life since I was very young.”

Despite this family influence, she says, “I thought I would be following a family tradition and become an artist, but I was always interested in science and did well in it. I thought art would be my career and that science would be my hobby, my side line. I realized if I pursued art, though I couldn't do science, in China. But, I could never leave science behind.”

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So You Think You’re Exhausted? War-Weary T Cells Have Us All Beat

Wherry Immunity image Dec 12This time of year has me pretty run down, with birthdays, holidays, concerts, you name it -- all manner of good and bad stress that weighs on one’s immune system. But I never knew my T cells could get exhausted, too. Two papers from the lab of E. John Wherry, PhD, associate professor of Microbiology and director of the Institute for Immunology at Penn, have taught me otherwise.

When you get a short-lived, acute infection, such as a flu bug, the body generally responds with a coordinated response, rapidly clearing the offending pathogen. Then, their mission done, immune cells stand down, leaving a core population of cells in case of re-infection. 

But what about long-term, chronic infections such as hepatitis C, HIV, and malaria? With these infections, the body and the pathogen essentially fight to a prolonged stalemate, neither able to gain an advantage. Over time, however, the battle-weary T cells become “exhausted,” giving the pathogen the edge.

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Dynamic Clots Make for Dynamic Research

Weisel platelets cover 2012“We showed for the first time that clotting is reversible,” says John Weisel, Ph.D., professor of Cell and Developmental Biology, in contrast to a long-standing assumption that it isn’t. Weisel and colleagues showed how these sometimes dangerous knots of protein and cells are actually a dynamic, mutable structure this month in Scientific Reports, a new Nature journal. Clotting is both a necessary function to stem blood loss, but in other dire circumstances can ultimately cause death.

In the last month since the paper has been online it has already risen to be the fifth-most-read paper in the journal in the past four weeks.

What makes this seemingly simple finding about the reversibility of clots so astounding is that researchers have tacitly assumed that clots and thrombi are stable structures until they fulfill their functions and are digested by the body. On the contrary, the Penn team found, using “fluorescence recovery after photobleaching,” that fibrin molecules come and go in clots, making them dynamic structures.

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A “Modest Proposal:” Spreading the Wealth from Intellectual Property to Encourage New Players in Drug Development

Garret FitzGerald April 2012 lab SLPGarret FitzGerald, MD, chair of the Department of Pharmacology and Director of the Institute for Translational Medicine & Therapeutics, Perelman School of Medicine at the University of Pennsylvania, has long said the current drug-development system in the United States is in need of change, “representing an unsustainable model.” He suggests a new model for sustainability, inspired by the not-for-profit sector.

The present approach to drug development is unsustainable - roughly the same number of drugs have been approved by the Food and Drug Administration each year since 1950 while the estimated cost, mostly because of the failure to bring new medicines all the way to market - has exploded. Many groups – most recently the President’s Council of Advisors on Science and Technology (PCAST) have mulled over the problem and issued reports. The last recommendation of the one from PCAST, in which I was involved, suggests setting up a working group to re-examine incentives that might foster more efficient drug development.

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What Would Dr. Cohn Think?

Cohn floral Dress Goddard 80sThis month marks three years since the late Mildred Cohn, PhD, the Benjamin Rush Professor Emerita of Physiological Chemistry at the time of her retirement from the Penn department of Biochemistry and Biophysics, passed away. Her early work using magnetic forces to study the structure of molecules led to the development of modern day magnetic resonance imaging, a mainstay of medical research and practice.

Ever since I watched the video about her life from the new Chemical Heritage Foundation’s series Women in Chemistry, I have thought each time I read a new article about gender and science, “What would Dr. Cohn think?”

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Lowering the Age of Scientific Independence

Sonnenberg horizontal lab 3 Sept 12Just over five years ago, Greg Sonnenberg, PhD, research associate in the Division of Gastroenterology and the Institute for Immunology, was tossing his mortarboard in the air at his now undergraduate alma mater SUNY Buffalo. This month, he will be starting his first independent research position, all before turning 30, effectively bypassing the ubiquitous postdoctoral phase of a typical career in biomedical research.  

The length of the “training period” and therefore age at which early career researchers establish independent research careers, has been steadily lengthening. According to the NIH Biomedical Research Workforce Working Group, the median age at which biomedical scientists start their first tenure-track position is 37. To address the family- and career-stymieing aspects of this trend, the NIH established the NIH Director's Early Independence Award (EIA) for exceptional early-career scientists to move directly into independent research positions by essentially omitting the traditional post-doctoral training period.

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NIH MERIT Awards Give Researchers Long-term Stability

Millar Dev Cell image Nov 10
Horizontal section through the basal layer of newborn mouse epidermis. Matthew LeBoeuf, UPenn
Earlier this summer, Sarah Millar, PhD, professor of Dermatology and Cell and Developmental Biology, received an unusual phone call from Carl Baker, MD PhD, Health Scientist Administrator at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). “So, Sarah, we’ve recommended that you receive a MERIT Award. Do you have any idea what that is?” asked Dr. Baker. Millar guessed that anything termed “MERIT” might possibly be good news, but admitted she had no idea what it actually meant.

It turns out that several Penn Med professors presently have these prestigious awards, in a wide range of topics, including natural reservoirs of SIV, simian immunodeficiency virus; regulation and function of thyroid hormone receptors; and genomic analysis of Alzheimer’s disease genes.

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Reconciling ENCODE and CODIS

DNA image From tmkeesey httpwww.flickr.comphotoskeesey3746669149The use of DNA in forensics is powerful yet subject to uncertainties. Jennifer Wagner, JD, PhD, a Research Associate at the Center for the Integration of Genetic Healthcare Technologies at the University of Pennsylvania (Penn CIGHT), and Sara Katsanis, MS, an Associate in Research at the Duke Institute for Genome Sciences & Policy at Duke University (Duke IGSP) conducted an exhaustive search of the literature and genome databases to put forensic markers used in the Combined DNA Index System (CODIS) into a context of current understanding of the human genome. Their findings are available in an early online issue of the Journal of Forensic Sciences (“Characterization of the Standard and Recommended CODIS Markers”) and a Letter (“Out with the ‘Junk DNA’ phrase”).

CODIS is a DNA database funded by the FBI. It stores DNA profiles created by crime labs and is searchable to aid in identifying suspects in crimes. The database is comprised of DNA profiles that are indicative of a person's individual DNA, enough to infer identity but not a person’s traits and conditions. The profiles consist of sequences of variable DNA repeats, most notably ones called “short tandem repeats” or, simply, “STRs.”

Recently we have seen a tsunami of coverage of dozens of papers in major scientific journals describing a ten-year project to decipher the non-coding portions of the human genome. This well-orchestrated release of scientific reports came out the same week the Journal of Forensic Sciences paper appeared online. Wagner and Katsanis explain how their work relates to this news.

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Scientists Who Bridge the Gap: “Rare Birds Indeed”

This summer, Garret FitzGerald, MD, chair of the Institute for Translational Medicine and Therapeutics (ITMAT), testified at a briefing on the Hill organized by American Association for the Advancement of Science that the current drug-development system in the United States is flawed and in need of change.

In short, it’s because of a long-term problem that many have been writing about - the number of new drugs getting to market has remained the same for decades, while costs have skyrocketed. And, to boot, the system of bringing new drugs to patients is extremely expensive and inefficient. Not to mention the regulatory and intellectual property reform that’s needed.

"This represents an unsustainable model," he said, and to change it, "we need to unlock translational opportunities afforded by science."

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Taking Advantage of Mother Nature, Delivering Drugs using Red Blood Cells

Weisel Science cover SEM thrombus July 09
Scanning EM of a coronary artery thrombus taken from a patient who had a heart attack. Fibrin fibers are brown; platelet aggregates are gray; red blood cells in red; leukocytes in green. John Weisel
What could be better than a natural, compatible, long-lived cell for delivering drugs to other cells in the body? Red blood cells fit this description and could be ideal at carrying drugs to specific targets. They play well with cells of the immune system, circulate for hundreds of days in the body; and can be loaded with all manner of cargo: peptides, modified full proteins, or small organic molecules.

In the 1980s, during the early stages of development of this field, HIV-related safety issues associated with blood transfusion forced many investigators to focus on synthetic carriers instead of red blood cells (RBCs). Nevertheless, several groups in the US and Europe are now working to take advantage of the unique properties of RBCs, which are much more compatible with the body than any synthetic carrier.

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It’s a Matter of Presentation

Marks Immunity blog post graph abstract AP3
AP-3 in dendritic cells. Credit: Michael Marks, PhD, Perelman School of Medicine; Immunity

A year ago this month, Penn Medicine announced the formation of the Penn Center for Orphan Disease Research and Therapy. Perelman School of Medicine researchers are currently conducting nearly 300 research projects on rare/orphan diseases, with nearly a third of those at the preclinical stage, looking at molecular intricacies at the cellular level before a full-blown clinical trial.

Case in point: A research article in a recent issue of Immunity from the lab of Mickey Marks, PhD, professor of Pathology and Laboratory Medicine, in part explains the recurrent bacterial infections in patients with a rare genetic disease called Hermansky-Pudlak Syndrome (HPS) type 2. Symptoms include albinism, prolonged bleeding, pulmonary fibrosis, and recurrent infections by both viruses and bacteria. Previous work on these patients and related mouse models had documented defects in killer T cells that attack virally infected cells and in other cell types that produce antiviral factors, but the recurrent bacterial infections had remained unexplained.

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Redirecting T Cells to Fight Cancer

June Immunocore cell image Oct 10
Non-specific T cells (blue) recognize and kill target melanoma cells (red) but ignore non-target cells (green) in the presence of the drug, IMCgp100. Credit: Immunocore Ltd.
Our immune response is very effective at controlling most early and developing cancers. However, once cancer can be detected as a mass, tumor cells have very often evolved in their own version of natural selection to evade a patient’s immune system. 

Over time, tumors develop different strategies to thwart the immune system.  One way involves tumor cells becoming less visible to the immune system by altering and/or turning off biological processes that present proteins to immune cells. A second way is by establishing a potent immune-suppressive environment around the tumor. For example, pancreas tumor cells produce a molecule that attracts inflammatory cells to cloak the tumor, thereby preventing other immune cells from killing the cancer cells

These obstacles make for a very difficult environment in which T cells can effectively attack tumors. In this regard, immunologists such as Michael Kalos, PhD, Director of the Translational and Correlative Studies Laboratory at Penn Medicine, are building a war chest of approaches to enhance the ability of T cells to attack as many cancer types as possible.

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Mutations in a Common Molecular Motor Cause Rare Diseases

Holzbaur Neuron blog post image June 12
The CAP-Gly domain of p150 subunit of dynactin is required for initiation of dynein loading at plus ends. Cronin & Schwartz, Neuron, Vol. 74: 2, pp 211-213.
It never ceases to amaze me how news about the rare has the potential to inform the common. Researchers from the lab of Erika Holzbaur, PhD, study molecular motors -- proteins that function as tiny molecular machines to move cargos within a cell. For the last few years, Holzbaur, a professor of Physiology at the Perelman School of Medicine, University of Pennsylvania, has been using live-cell imaging to get a better handle on what happens when the transport of cellular cargo goes off track, and how that may be the start of neurodegenerative diseases. In this case, a Parkinson’s-like disorder and a hereditary form of motor neuron disease (MND).  

In a recent study published in Neuron, Holzbaur and graduate student, Armen Moughamian, studied mutations in the molecular motor cofactor dynactin that are associated with Perry syndrome, an extremely rare, inherited neurodegenerative disease. Parkinson’s disease-like symptons and psychiatric changes are the predominant features of this syndrome. The dynactin complex is conserved from yeast to humans, and mutations in it not only cause Perry syndrome, but also cause a form of MND, called distal hereditary motor neuropathy 7B. 

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Among the “Unsung Heroes” of Patient Care

PLM NationalLabWeek_2012_forWebThe Department of Pathology and Laboratory Medicine (PLM) is celebrating National Medical Laboratory Professionals Week April 22 to 28. Medical laboratory professionals are among the unsung heroes of patient care - the team behind the scenes who are “doing the best with every test.” 

While you may never meet them in person, laboratory technologists are an integral and important part of your health care. Many of your physician’s decisions for your primary or specialized care will depend on the expertise and advice from clinical labs in some way. 

Pathologists and lab technologists supervise and perform laboratory tests on blood and tissue specimens collected from patients. These test results are used to help make diagnoses and prescribe medications. Laboratory personnel prepare individualized reports and determine which tests can provide additional information. They may also consult with your physician or clinical programs on your future care and treatment.

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What’s Happening the Rest of the Week at the Philadelphia Science Festival?

CIMG4426The Philadelphia Science Festival Carnival tents have all been folded and hauled away. There have already been four nights of non-stop science cafes at local watering holes. But, there are still six more days of the festival to go, and Penn Medicine faculty will be participating at events on most of those days.

Tonight, Tuesday, April 24, come hear about the The Great Vaccine Debate, 6:30 p.m., The Academy of Natural Sciences of Drexel University, 1900 Benjamin Franklin Parkway. For more than two centuries, vaccines have protected us against many of humankind’s deadliest diseases, prevented global epidemics, and saved countless lives. Yet, in recent years a debate has sprung up on the safety of vaccination, causing some parents to forgo vaccinating their children. This has led to the return of some diseases, such as whooping cough and measles, as we begin to lose our “herd” immunity. Hear the real scoop from a panel of vaccine scientists, medical ethicists, and Mark Largent, PhD, author of Vaccine: The Debate in Modern America. Jason Schwartz, associate fellow at the Penn Center for Bioethics, is a panelist.

Sometimes the world needs a superhero. On Wednesday, April 25, attend Science Super Heroes, 7:00 p.m., Chemical Heritage Foundation, 315 Chestnut Street, to meet a few Penn, Philadelphia University, and Temple scientists who are doing great things, from repairing oil spill damage to curing once-fatal diseases. Doug Smith, MD, director of the Center for Brain Injury and Repair, is a panelist.

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Hat Trick for Penn Medicine at Philadelphia Science Festival this Monday

PSF logoOn Monday, April 23, Penn Medicine faculty will be particpating in three events at the Philadelphia Science Festival.

Start off with the science café Orphan Diseases: What Are They and Why Should We Care? at Rembrandt’s, 741 North 23rd Street at 6:30 PM. Hear firsthand the plight of a patient who fought to be diagnosed with an "orphan disease," and what some Philadelphia scientists are doing to help change the fate of the 30 million Americans with rare diseases. FOP expert Fred Kaplan, MD, Orthopedics, is part of the panel discussion in this event organized by the Monell Chemical Senses Center.

Also the Franklin Institute is hosting the public lecture Cancer and our Genome: Insight and Hope at 6:00 PM. This free event features Penn cancer experts Drs. Chi Van Dang, Katherine Nathanson, and Anil Rustgi, as well as Yael Mosse from the Children’s Hospital of Philadelphia and Ashani Weeraratna from the Wistar Institute. The discussion will be emceed by WHYY’s Taunya English and is organized by the Penn Genome Frontier Institute.

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Philadelphia Science Festival Starts this Weekend!



PSF logoIt's less than a week away! The Festival, a citywide collaboration showcasing science and technology every April, will run from April 20-29. Penn students, staff, and faculty will be participating in all kinds of events throughout the entire festival. For the next two weeks, watch this news blog and Penn Medicine on Twitter and Facebook for detailed information on individual Penn events.

To start, on the first night of the Festival, Friday, April 20, Ben Stanger, a Penn cancer biologist who studies tissue regeneration, and amphibian biologist Carlos Martinez Rivera from the Philadelphia Zoo, will be part of a science café called Bringing Up Baby at 6:30pm at Rembrandts restaurant, 741 North 23rd Street. It’s free! No registration, so just show up!

 

The speakers will explore what all animal life on our planet – starting out as a single cell, the product of a sperm and an egg – has in common. They will guide the audience through the amazing set of events that led each one of us to be here, viewed from the worlds of molecular biology, cell biology, and zoology, with a Q&A session to follow.

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Penn Med at the Science Festival!

PSF_logo_RGBPenn Medicine will play a starring role in the Philadelphia Science Festival again this year. The Festival is a citywide collaboration showcasing science and technology every April. 

This year it runs from April 20-29 -- 10 days to celebrate the region’s strengths in science and technology, bringing together more than 105 partners from academia to museums to restaurants. The Festival will include an extensive line-up of programs and exhibitions designed to inspire the next generation of scientists and spark discussion among young and old. 

Penn Medicine students, staff, and faculty will be participating in a free public outdoor carnival on the Parkway, Science Night at the Ballpark with the Phillies, and a Science Film Fest throughout the entire week. 

PSF carnival11_0[1]

Penn Med folks will also be part of discussing lively topics during “science cafes” at local restaurants; educating visitors about our medical history during a scavenger hunt in Old City; and discovering science in our own back yard at Science Day in Clark Park.

Building on Philadelphia’s rich history of innovation with dozens of events at museums, universities and neighborhood libraries, the Festival offers something for everyone. Learn more about about all of the festival activities, how to register for free events, buy tickets for other events, or volunteer to be part of the action.

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Cell Home Movies

Studying live cells must be the ultimate for physiologists. Imagine seeing the inner workings of a cell instead of static, stained snap shots of processes over some period of time. It’s like seeing a favorite book whose scenes you’ve played out in your head come alive on a movie screen.

Holzbaur JCB Model for blog post Mar 12

 

 

The lab of Erika Holzbaur, PhD, has been studying molecular motors  -- proteins that function as tiny machines within a cell -- for almost two decades. For the last few years they have been using live-cell imaging to get a better handle on what happens when the transport of cellular cargo goes off track, and how that may be the start of certain neurodegenerative diseases.

Autophagy, literally self-eating, is an essential cellular process for recycling proteins and organelles. It’s complicated and involves the formation of sacs called autophagosomes that engulf the proteins to be degraded in one part of the cell; the proteins’ transport along microtubule tracks by the molecular motor dynein to another area, and the degrading of proteins into basic amino acids in a mature sac called an autolysosomes. Mislocation of the protein tau – the cross ties of the microtubule railroad on which the trash sacs move -- in some neurodegenerative diseases may disrupt normal nourishment and waste removal in nerve cells.

In a recent Journal of Cell Biology study Holzbaur, a professor of Physiology, postdoctoral researcher Sandra Maday, Ph.D., and Karen E. Wallace, all from the Perelman School of Medicine, examined autophagosomes in neurons from transgenic mice reared with a handy florescent green biomarker. These neurons, when grown in culture, send out axon-like projections, which grew 1 mm in two days, making it easier for the team to record movies of the sacs moving along the projection.

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To Sleep, Perchance to Synthesize Proteins

Sleep keeps neuroscientist Marcos Frank, PhD awake, studying the importance of slumber during early life when the brain is rapidly maturing and highly changeable. Building on his research showing that the brain during sleep is fundamentally different from the brain during wakefulness, Frank has found that cellular changes in the sleeping brain may promote the formation of memories. The world as the brain sees it. Optical ‘polar’ maps of the visual cortex. Credit: Marcos Frank, PhD
When an animal goes to sleep it's like a switch is thrown, he says, and everything is turned on that's necessary for making synaptic changes that form the basis of memories. The team used an animal model of cortical plasticity – the making and breaking of neural connections -- in response to visual cues. 

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Stretched to the Breaking Point

:  Like beads on a string, periodic swellings can appear on nerve fibers called “axons” after traumatic injury.  At each swelling site, there is mechanical breakage of individual microtubules that act as “railroad tracks” within the axons, causing accumulation of their transported cargoes.   Breakage of different microtubules at different locations along the axons results the periodic arrangement of the swellings.  This represents a newfound process of “partial interruption of axonal transport” found after axon stretch injury in culture (top two panels) and in humans with traumatic brain injury (bottom panel).

With this year’s Super Bowl setting a record for being the most-viewed show in U.S. television history, concussions – more technically, mild traumatic brain injury (TBI) – have probably been on many a mind this week. TBI has long been a leading cause of death and disability, with over 1.7 million cases in the US alone each year.
 
Misshapened, swollen nerve fibers called axons in the post-mortem brain tissue of TBI patients have been noted by pathologists for years. They assumed the swellings arose from a complete interruption in what the axons were normally transporting between nerve cells. Due to their elastic nature, white-matter axons are susceptible to damage by the stretch and strain produced during TBI.
 
Using a high-powered microscope called TEM, for transmission electron microscopy, a team from Penn Medicine viewed damaged axons in two ways to gain a better idea of what causes the damage: in those grown in the lab and stretched mechanically and in those from post-mortem samples from TBI patients. In both types of axons, they found at each site of swelling mechanical breakage of individual microtubules – tubes for transporting proteins within a cell. This break in the cell’s transport system causes accumulation of the protein cargo. Breakage of different microtubules at different locations on the axons can also cause a series of swellings along the entire length, creating the appearance of beads on a string.

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“A Culture of Collegiality”: Research Collaboration Leads to Stronger Outcome for Basic Science of Schizophrenia

Translational Research in Action

Smilow Center for Translational Research

In the spring of 2011, Penn celebrated the opening of the Smilow Center for Translational Research – a new home for Penn Medicine's emphasis on translating breakthroughs in the lab to clinical therapies for patients. The story profiled here is just one example of such research at Penn.

See more stories in this series.

According to the National Institute for Mental Health (NIMH), up to one quarter of adults are diagnosed for a disorder annually in the United States. Although mental disorders are widespread in the population, the main burden of illness is concentrated among a smaller proportion (about 6 percent, or 1 in 17) who suffer from a seriously debilitating mental illness.

Despite the scope of such disorders, researchers are only beginning to understand the underlying neurobiological causes of these diseases. At the last Society for Neuroscience meeting, in late 2011, many presentations addressed these issues.

Closer to home, work from a team at Penn was featured on the cover of a recent Proceedings of the National Academy Sciences. The article was authored by nine members of the Department of Psychiatry, in the Perelman School of Medicine. Their collective work connects reductions in a brain protein that has been identified as a possible risk factor for schizophrenia – dysbindin – and illustrates how disruption in this protein leads to impairments in how the brain processes sensory stimuli such as sound.

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The Whole Enchilada: New Method for High-Res Brain Images

When comparing GluCEST imaging (middle panel) of healthy human brains with other methods (PET), more details in the landscape of white matter (green/yellow) and gray matter (red) of the whole brain were revealed using the GluCEST method. Ravinder Reddy, PhD, Perelman School of Medicine; Nature Medicine

Magnetic resonance imaging (MRI) provides exquisite structural detail of the brain. However, current MRI methods can't image the detailed distribution of neurotransmitters – the brain’s chemical messengers -- across the whole brain.

Current imaging techniques for glutamate, a major neurotransmitter, is anything but perfect, but it still lets physicians and researchers gain fleeting glimpses into one of biology’s greatest mysteries: the inner workings and connectivity of the human brain.

A new Nature Medicine paper out this week from Perelman School of Medicine researchers led by Ravinder Reddy, PhD, professor of Radiology, describes a first-of-its-kind MRI technique (GluCEST) to measure glutamate concentration and local changes across the whole brain. The technique is based on chemical exchange effects on water proton MRI.

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An Epilogue to a Protein Saga – But Not the Last Word

A high magnification image of the cortical brain region from a dementia patient diagnosed with frontotemporal lobar degeneration with TDP-43 pathology. TDP-43 clumps were detected by immunohistochemistry using anti-TDP-43 antibodies (brown color).  The TDP-43 clumps were shown to contain disulfide cross-linking suggesting they result from oxidative stress in the brain. Todd Cohen, PhD, Perelman School of MedicineEvery saga needs occasional updates. TDP-43 -- a protein important in gene expression that can undergo pathologic misfolding -- is no different. Earlier reports on the protein were outlined in a Penn Med news blog, which describes its pathology and genetics related to neurodegenerative disease. But now the field is maturing and researchers are linking TDP-43 to a well-established clinical area - the role of oxidative stress in the demise of nerve cells.

A major hurdle in understanding neurodegenerative disease is gaining a clear picture of what leads up to neuron death. In recent years, much data has been published indicating that increased oxidative stress plays a role in neuron degeneration and death. Oxidative stress is an imbalance between the production of reactive oxygen molecules and the body's ability to get rid of them. Disturbances in the normal oxygen state of tissues can damage all components of the cell, including proteins and DNA.

Most recently, Todd Cohen, PhD, a postdoctoral fellow in the lab of Virginia M.Y. Lee, PhD at Penn’s Center for Neurodegenerative Disease Research, studied how TDP-43 reacts to oxidative stress, published in the EMBO Journal in December. Stress induces the protein to move from the nucleus to the cell cytoplasm. Its ability to fold properly is also altered.

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Addressing Unmet Needs: The Science Behind Rare Cholesterol Diseases

Translational Research in Action

Smilow Center for Translational Research

In the spring of 2011, Penn celebrated the opening of the Smilow Center for Translational Research – a new home for Penn Medicine's emphasis on translating breakthroughs in the lab to clinical therapies for patients. The story profiled here is just one example of such research at Penn.

See more stories in this series.

How the rare informs the common is becoming a – well – more common theme in biomedical research. Working with people who have rare genetic conditions provides researchers with a unique window into learning the role specific genes play in more common diseases.

“Relating insights concerning the genetic basis of disease to the identification of novel therapeutic targets and then developing new therapies that address unmet medical needs is one hallmark of translational medicine,” explains Daniel J. Rader, MD, professor of Medicine and Pharmacology, and associate director of the Institute for Translational Medicine and Therapeutics at the Perelman School of Medicine at the University of Pennsylvania.

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A Medical Translation Long in the Making: From a Millennia-Old Mutation to New Hope for Treating AIDS

Translational Research in Action

Smilow Center for Translational Research

In the spring of 2011, Penn is celebrating the opening of the Smilow Center for Translational Research – a new home for Penn Medicine's emphasis on translating breakthroughs in the lab to clinical therapies for patients. The story profiled here is just one example of such research at Penn.

See more stories in this series.

Efforts to bring new treatments to patients more quickly often draw from disparate quarters and this one has it all: A miraculous recovery of an AIDS patient, a previously unrecognized ancient genetic mutation, and new hope for a deadly disease based on a molecular scissors, of sorts.

A genetic mistake that arose thousands of years ago spares rare HIV-infected individuals the ravages of AIDS. The mutation in a protein that sits on the surface of a human immune cell renders one percent of Caucasians alive today resistant to HIV infection. Researchers believe that strong natural selective pressures in the past favored individuals with this mutation.

Many labs are trying to develop approaches to cure HIV based on this rare mutation, and Penn’s School of Medicine is one of those in the midst of translating the language of ancient genetic mistakes into today’s cures.

In late 2008 an unexpected clinical development emphasized the potential for applications based on this mutation. An HIV-positive American living in Berlin, who also had leukemia, which is best treated by a bone marrow transplant, was seemingly cured of HIV. He was given marrow from a tissue-matched donor who had also been screened for the genetic mutation conferring resistance to most types of HIV. At the time of international reports on the success of his treatment, the patient had lived close to 20 months since the transplant with no detectable traces of HIV in his marrow, blood, or other tissues. He remains healthy today.

A genetic resistance to HIV Infection

The donor, born with the mutation in his CCR5 gene, did not have a working CCR5 receptor protein on the surface of his T cells. The CCR5 protein is one of the two cell-surface receptors needed for HIV to gain entry into a T cell in order to replicate. The mutation prevents HIV from attaching itself to cells. Individuals with the mutated CCR5 are seemingly not affected by the non-functional CCR5 protein, other than their resistance to HIV. (In fact, James Hoxie, MD, director of the Penn Center for AIDS Research, whose genome harbors the CCR5 mutation, was profiled in The Scientist last year about his unique genetic status.)

Much of the basic work behind understanding CCR5’s role in HIV infection came from the lab of Robert Doms, MD, PhD, chairman of Penn’s Department of Microbiology, and colleagues who in 1996 described CCR5’s relationship with HIV

Engineering HIV-Resistant T-Cells

In research beginning in 2004, researchers at Penn’s School of Medicine and collaborators from Sangamo BioSciences in Richmond, CA, took a first step toward engineering normal T cells to mimic those that have natural HIV resistance.

Zinc finger image courtesy of Sangamo Zinc fingers are proteins that normally bind to different bases in the DNA sequence to regulate the activity of genes. The zinc fingers used in this experiment were custom-designed to bind to specific DNA sequences in the CCR5 gene. The zinc finger protein acts as a molecular scissors, bringing a DNA enzyme to the CCR5 gene to cut a portion of its sequence, but due to the repair process a new mutation arises in the CCR5 protein, rendering it non-functional. Without a functional CCR5 protein on the cell's surface, HIV cannot enter, leading to resistance to HIV infection. Once the modification is made to the cell’s CCR5 gene it is permanently disrupted in that cell and even in its progeny. The door to HIV’s entry into the T cell is slammed shut, and if the cells are induced to divide, a form of spreading HIV resistance can result.

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The On-Going Saga of a Disease Protein

Misfolded TDP-43 proteins in neurons of brain tissue (brown structures indicated by arrows)  Credit: Felix Geser, MD, PhD, University of Pennsylvania School of Medicine. Misfolded TDP-43 proteins in neurons of brain tissue (brown structures indicated by arrows) Credit: Felix Geser, MD, PhD, University of Pennsylvania School of Medicine.

Science, if anything, is incremental. It's a slow accumulation of knowledge punctuated by Eureka moments. As the years go by, one of my favorite aspects of working in science communications is watching how discoveries unfold - literally and figuratively, in the case of TDP-43, a normal protein that undergoes pathologic misfolding in the disease state.

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