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News Archive: 2011-2012

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DECEMBER 17, 2012 - Penn Researchers Show Cocaine Addiction Resistance May Be Passed Down from Father to Son

New research from the Perelman School of Medicine at Penn and Massachusetts General Hospital (MGH) reveals that sons of male rats exposed to cocaine are resistant to the rewarding effects of the drug, suggesting that cocaine-induced changes in physiology are passed down from father to son. The findings are published in the latest edition of Nature Neuroscience.

“We know that genetic factors contribute significantly to the risk of cocaine abuse, but the potential role of epigenetic influences, how certain genes related to addiction are expressed, is still relatively unknown,” said senior study author R. Christopher Pierce, PhD, associate professor of Neuroscience in Psychiatry at Penn. “This study is the first to show that the chemical effects of cocaine use can be passed down to future generations to cause a resistance to addictive behavior, indicating that paternal exposure to toxins can have profound effects on gene expression and behavior of their offspring.”

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NOVEMBER 2012 - Dr. Steven Fluharty Delivers Capital Hill Briefing on the Impacts of Sequestration

Steven J. Fluharty, Ph.D. is a Professor of Pharmacology, Psychology and Neuroscience and the Senior Vice Provost for Research at the University of Pennsylvania. In this capacity Dr. Fluharty shapes policy and advances administrative initiatives for the University’s billion dollar research enterprise as well as plays a leadership role in strategic planning for research and administers the development of new research facilities. He also helps to oversee campus-wide research planning efforts, linkages between the University and industry, and the transfer of technologies from University laboratories to the public sector. In addition, he governs the research activities of Provostial Centers and Institutes, particularly those involving interdisciplinary collaboration.

 

NOVEMBER 16, 2012 - Yeast Protein Breaks up Amyloid Fibrils and Disordered Protein Clumps In Different Ways

Several fatal brain disorders, including Parkinson's disease, are connected by the misfolding of specific proteins into disordered clumps and stable, insoluble fibrils called amyloid. Amyloid fibrils are hard to break up due to their stable, ordered structure. For example, a-synuclein forms amyloid fibrils that accumulate in Lewy Bodies in Parkinson's disease. By contrast, protein clumps that accumulate in response to environmental stress, such as heat shock, possess a less stable, disordered architecture.

Hsp104, an enzyme from yeast, breaks up both amyloid fibrils and disordered clumps. In the most recent issue of Cell, James Shorter, PhD, assistant professor of Biochemistry and Biophysics, and colleagues show that Hsp104 switches mechanism to break up amyloid versus disordered clumps. For stable amyloid-type structures, Hsp104 needs all six of its subunits, which together make a hexamer, to pull the clumps apart. By contrast, for the more amorphous, non-amyloid clumps, Hsp104 required only one of its six subunits.

Unexpectedly, the bacterial version of the Hsp104 enzyme, called ClpB, behaves differently compared to Hsp104. Bacterial ClpB uses all six subunits to break up amorphous clumps and fails to break up amyloid fibrils. Bacteria just ignore these more stable structures, whereas yeast use Hsp104 to exploit amyloid fibrils for beneficial purposes.

“One surprise is that biochemists thought that Hsp104 and ClpB hexamers worked in the same way,” says first author and graduate student in the Shorter lab Morgan DeSantis. “This is not the case.”

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NOVEMBER 15, 2012 - Parkinson's Disease Protein Causes Disease Spread and Neuron Death in Healthy Animals

Lee & LukUnderstanding how any disease progresses is one of the first and most important steps towards finding treatments to stop it. This has been the case for such brain-degenerating conditions as Alzheimer's disease. Now, after several years of incremental study, researchers at the Perelman School of Medicine, University of Pennsylvania have been able to piece together important steps in how Parkinson’s disease (PD) spreads from cell to cell and leads to nerve cell death.

In short, the Penn researchers found that, in healthy mice, a single injection of synthetic, misfolded α-Syn fibrils led to a cell-to-cell transmission of pathologic α-Syn proteins and the formation of Parkinson’s α-Syn clumps known as Lewy bodies in interconnected regions of the brain. Their findings appear in this week’s issue of Science. The team was led by senior author Virginia M.-Y Lee, PhD, director of the Center for Neurodegenerative Disease Research (CNDR) and professor of Pathology and Laboratory Medicine, and first author Kelvin C. Luk, PhD, research assistant professor in the CNDR.

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NOVEMBER 13, 2012 - NIH Awards Penn Scientists $10 million Over Five Years for Innovative Research on Single Cells

Eberwine & KimJames Eberwine, PhD, Elmer Holmes Bobst Professor of Pharmacology in the Perelman School of Medicine, and Junhyong Kim, PhD, Edmund J. and Louise W. Kahn Professor of Biology in the School of Arts and Sciences, will be studying the role of how messenger RNA (mRNA) molecules vary in their function in individual cells with a five-year, $10 million grant from the National Institutes of Health (NIH). Their award is supported by the NIH Common Fund and is part of three initiatives of the Single Cell Analysis Program (SCAP). Eberwine and Kim are also Co-directors of the Penn Genomic Frontiers Institute.

The goal of the Penn grant is to characterize the variability in identity and abundances of RNA molecules that are transcribed from the genome of human neurons and heart cells. These are the so-called excitable cells, those that use bioelectricity for communication and everyday functions. Many human nervous system diseases derive from changes in electrical responsiveness of neurons and heart arrhythmias account for many heart-related deaths.

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NOVEMBER 13, 2012 - Targeting Downstream Proteins in Cancer-Causing Pathway Shows Promise in Cell, Animal Model, Penn Study Finds

The cancer-causing form of the gene Myc alters the metabolism of mitochondria, the cell’s powerhouse, making it dependent on the amino acid glutamine for survival. In fact, 40 percent of all “hard-to-treat” cancers have a mutation in the Myc gene. Accordingly, depriving cells of glutamine selectively induces programmed cell death in cells overexpressing mutant Myc.

Using Myc-active neuroblastoma cancer cells, a team led by Howard Hughes Medical Institute (HHMI) investigator M. Celeste Simon, Ph.D., scientific director for the Abramson Family Cancer Research Institute (AFCRI), identified the proteins PUMA, NOXA, and TRB3 as executors of the glutamine-starved cells. These three proteins represent a downstream target in the Myc pathway at which to aim drugs. Roughly 25 percent of all neuroblastoma cases are associated with Myc-active cells.

The findings appear in this week’s issue of Cancer Cell. Simon is also a professor of Cell and Developmental Biology at the Perelman School of Medicine, University of Pennsylvania. The Penn team collaborated with colleagues from The Children’s Hospital of Philadelphia (CHOP) John Maris and Michael Hogarty.

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NOVEMBER 9, 2012 - A Comparative Medicine Study by Penn Vet Identifies a New Approach to Combat Viral Infections

When a virus such as influenza invades our bodies, interferon proteins are among the first immune molecules produced to fight off the attack. A study by scientists from the University of Pennsylvania School of Veterinary Medicine offers a new strategy for enhancing the effects of interferon in fighting off infection. The research suggests that, by targeting a particular molecule in the interferon signaling pathway, specially designed drugs may be able to boost the activity of a person’s own interferon, augmenting the immune system’s fight against viruses. It’s possible that the same drugs might also be effective against some types of cancer and certain autoimmune conditions.

FuchsSerge Fuchs, a professor of cell biology in Penn Vet’sDepartment of Animal Biology and director of the School’s Mari Lowe Comparative Oncology Center, was the senior author on the paper published in theProceedings of the National Academy of Sciences.

“The practical significance of our study is a demonstration of the ability to use emerging pharmaceuticals to reactivate an individual’s own interferon or to use a reduced dose to get the same effect,” Fuchs said.

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NOVEMBER 2, 2012 - New Medication Shows Promise as Lipid-Lowering Therapy for Rare Cholesterol Disorder, Penn Study Finds

An international effort led by researchers at the Perelman School of Medicine at Penn has resulted in positive phase 3 clinical trial results for a new medicine to treat patients suffering from a rare and deadly cholesterol disorder. Penn researchers report in The Lancet that lomitapide, a first-in-class microsomal triglyceride transfer protein (MTP) inhibitor, substantially and stably reduced LDL cholesterol (the “bad” cholesterol) in patients with the orphan disease homozygous familial hypercholesterolemia (HoFH). Lomitapide works by inhibiting MTP, which is required for the production of VLDL — the precursor to LDL.

Senior study author Daniel J. Rader, MD, chief, Division of Translational Medicine and Human Genetics, has treated HoFH patients for more than two decades. In the early 1990s, Rader worked with colleagues to determine that mutations in MTP were the cause of a rare condition characterized by absent LDL in the blood, establishing MTP as a therapeutic target to reduce LDL. His colleagues then went on to discover the MTP inhibitor lomitapide at Bristol-Myers Squibb (BMS). Rader led a study at Penn in the late 1990s showing that lomitapide substantially reduced LDL in patients with moderately elevated LDL. However, because the agent caused some gastrointestinal side effects and increased liver fat, BMS decided to abandon further development of lomitapide for a much larger population of patients with elevated levels of cholesterol. Rader convinced BMS to donate the drug to Penn so that he could continue to develop it in patients with HoFH. Based on its mechanism and on a study in a rabbit model of the disease, Rader felt it would be effective against HoFH.

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OCTOBER 25, 2012 - New Evidence Suggests Certain Anesthetics Highjack the Brain's Natural Sleep Circuitry

A new study by researchers at the Perelman School of Medicine at the University of Pennsylvania demonstrates in an animal model that a commonly used inhaled anesthetic drug, isoflurane, works by directly causing sleep-promoting neurons in the brain to activate, thereby hijacking our natural sleep circuitry. The findings are the latest work by investigators in the Center for Anesthesia Research at Penn who are exploring how anesthetics interact within the central nervous system to cause a state of unconsciousness. Thenew research is published the latest edition of the journal Current Biology.

"Despite more than 160 years of continuous use in humans, we still do not understand how anesthetic drugs work to produce the state of general anesthesia," said study author Max B. Kelz, MD, PhD, assistant professor of Anesthesiology and Critical Care. "We show in this new work that a commonly used inhaled anesthetic drug directly causes sleep-promoting neurons to fire. We believe that this result is not simply a coincidence. Rather, our view is that many general anesthetics work to cause unconsciousness in part by commandeering the brain’s natural sleep circuitry, which initiates our nightly journey into unconsciousness."

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OCTOBER 25, 2012 - End of Life Decisions

Scott Halpern of Medicine discusses a new end-of-life studies center that researches one of “health care's most contentious and painful areas.”

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OCTOBER 15, 2012 - How Can You Protect your Brain as you Age?

Medicine's Virginia Lee and John Trojanowski discuss the need for drug discovery to combat the “natural disaster of our millennium,” neurodegenerative disease.


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OCTOBER 4, 2012 - Penn Researchers Create a Universal Map of Vision in the Human Brain

Aguirre labNearly 100 years after a British neurologist first mapped the blind spots caused by missile wounds to the brains of soldiers, Perelman School of Medicine researchers at the University of Pennsylvania have perfected his map using modern-day technology. Their results create a map of vision in the brain based upon an individual's brain structure, even for people who cannot see. Their result can, among other things, guide efforts to restore vision using a neural prosthesis that stimulates the surface of the brain. The study appears in the latest issue of Current Biology, a Cell Press journal.

"By measuring brain anatomy and applying an algorithm, we can now accurately predict how the visual world for an individual should be arranged on the surface of the brain," said senior author Geoffrey Aguirre, MD, PhD, assistant professor of Neurology. "We are already using this advance to study how vision loss changes the organization of the brain."

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September 28, 2012 - Penn Immunologists Find a Molecule That Puts the Brakes on Inflammation

We couldn’t live without our immune systems, always tuned to detect and eradicate invading pathogens and particles. But sometimes the immune response goes overboard, triggering autoimmune diseases like lupus, asthma or inflammatory bowel disease.

Christopher Hunter and Aisling O'Hara HallA new study led by Christopher Hunter, professor and chair in the Department of Pathobiology in Penn’s School of Veterinary Medicine and Aisling O’Hara Hall, a doctoral candidate in the Immunology Graduate Group, has now identified a crucial signaling molecule involved in counterbalancing the immune system attack.

“The immune response is like driving a car,” said Hunter. “You hit the accelerator and develop this response that’s required to protect you from a pathogen, but, unless you have a brake to guide the response, then you’ll just careen off the road and die because you can’t control the speed of the response.”

The study is published in the September issue of the journal Immunity.

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SEPTEMBER 26, 2012 - Penn Medicine Receives NIH Grant to Launch New Center for the Study of Sex and Gender in Behavioral Health

Researchers from the Perelman School of Medicine at Penn have been awarded a $3.7 million grant from the National Institutes of Health (NIH) to establish a new translational interdisciplinary research center to explore the role of sex and gender in behavioral health.

The new Center for the Study of Sex and Gender in Behavioral Health will be led by C. Neill Epperson, MD, associate professor of Psychiatry and founder and director of the Penn Center for Women's Behavioral Wellness, as principal investigator, along with Tracy L. Bale, PhD, Center co-director and associate professor of Psychiatry at the Perelman School of Medicine and director, Neuroscience Center at Penn's School Of Veterinary Medicine.

“It is well established that sex and gender are critical determinants of mental health and mental illness. But what isn’t clear is how hormonal developmental milestones such as puberty and early life traumatic events interact to impact neuropsychiatric health in women across the lifespan,” said Dr. Epperson. “Using behavioral and molecular models of stress and reproductive neuroendocrinology, psychophysiology, and neuroimaging, the new Center for the Study of Sex and Gender in Behavioral Health will investigate the unique mechanisms at play in women’s behavioral health.”

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SEPTEMBER 10, 2012 - Penn Team Finds Key Molecules Involved in Forming Long-term Memories

How does one’s experience of an event get translated into a memory that can be accessed months, even years later? A team led by University of Pennsylvania scientists has come closer to answering that question, identifying key molecules that help convert short-term memories into long-term ones. Joshua Hawk (right), now a postdoctoral research fellow at Yale University, led the study, which was conducted as part of his Ph.D. work in the Neuroscience Graduate Group at Penn. He worked with Ted Abel (left), PhD, Penn’s Brush Family Professor of Biology.

Abel & Hawk“There are many drugs available to treat some of the symptoms of diseases like schizophrenia,” Abel said, “but they don’t treat the cognitive deficits that patients have, which can include difficulties with memory. This study looks for more specific targets to treat deficits in cognition.”

Published in the Journal of Clinical Investigation, the study focused on a group of proteins called nuclear receptors, which have been implicated in the regulation of a variety of biological functions, including memory formation.

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SEPTEMBER 6, 2012 - Thickening of the Heart's Right Ventricle Could Foreshadow Heart Failure and Cardiovascular Death in Otherwise Heart-Healthy Patients, Penn Study Shows

Researchers at the Perelman School of Medicine at the University of Pennsylvania report in a new study that thickening of the heart’s right ventricle is associated with an increased risk of heart failure and cardiovascular death in patients without clinical cardiovascular disease at baseline. The study is published online ahead of print in the journal Circulation.

“In most studies of the heart, researchers have focused on the more-easily-imaged left ventricle, the region of the heart affected by systemic high blood pressure and other common conditions,” said study author Steven Kawut, M.D., M.S., associate professor of Medicine and Epidemiology and director of the Pulmonary Vascular Disease Program at Penn. “But we know from the results of this study and previous work that focusing attention on the right ventricle (RV) is critical in our understanding of many conditions of the heart and lungs. This research revealed that approximately one in 10 heart failure events and cardiovascular deaths may be attributed to thickening of the RV in adults without clinical cardiovascular disease at baseline.”

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AUGUST 13, 2012 - $4.6 Million Renewal from NIH to Penn Program that Aims to Diversify Biomedical Education

Paterson photoYvonne Paterson, PhD, professor of Microbiology (Cell & Molecular Biology and Immunology Graduate Groups), at the Perelman School of Medicine, and professor and associate dean, at the School of Nursing, has been awarded an almost $5 million renewal by the National Institute for General Medical Sciences for the University of Pennsylvania Postdoctoral Opportunities in Research and Training, or PENN-PORT, the postdoctoral-training program she leads.

This program funds 15 postdoctoral fellows who teach in local colleges and universities that have a significant minority enrollment. The PENN-PORT program combines a traditional, three-year postdoctoral research training with a two-year mentored teaching experience at one of three partner minority-serving institutions: Lincoln University, Rutgers University-Camden, and Delaware County Community College.

The goals of the postdoctoral program are to enhance research-oriented teaching at the partner institutions; to promote research collaborations between faculty members at the three partner institutions and Penn; and to encourage minority students to enter graduate school and increase minority participation in biomedical research.

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JULY 19, 2012 - Anti-Tau Drug Improves Cognition, Decreases Tau Tangles in Alzheimer's Disease Models, Penn Researchers Report

Penn Medicine research presented on July 19th at the 2012 Alzheimer's Association International Conference (AAIC) shows that an anti-tau treatment called epithilone D (EpoD) was effective in preventing and intervening the progress of Alzheimer's disease in animal models, improving neuron function and cognition, as well as decreasing tau pathology.

Trojanowski pic"This drug effectively hits a tau target by correcting tau loss of function, thereby stabilizing microtubules and offsetting the loss of tau due to its formation into neurofibrillary tangles in animal models, which suggests that this could be an important option to mediate tau function in Alzheimer's and other tau-based neurodegenerative diseases," said John Trojanowski, MD, PhD, (Neuroscience Graduate Group). "In addition to drugs targeting amyloid, which may not work in advanced Alzheimer's disease, our hope is that this and other anti-tau drugs can be tested in people with Alzheimer's disease to determine whether stabilizing microtubules damaged by malfunctioning tau protein may improve clinical and pathological outcomes."

Bristol-Myers Squibb, who developed and owns the rights to the drug, has started enrolling patients into a phase I clinical trial in people with mild Alzheimer's disease.

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JULY 1, 2012 - Penn Researchers Improve Living Tissues With 3D Printed Vascular Networks Made From Sugar

Researchers are hopeful that new advances in tissue engineering and regenerative medicine could one day make a replacement liver from a patient’s own cells, or animal muscle tissue that could be cut into steaks without ever being inside a cow. Bioengineers can already make 2D structures out of many kinds of tissue, but one of the major roadblocks to making the jump to 3D is keeping the cells within large structures from suffocating; organs have complicated 3D blood vessel networks that are still impossible to recreate in the laboratory.

Now, University of Pennsylvania researchers have developed an innovative solution to this perfusion problem: they’ve shown that 3D printed templates of filament networks can be used to rapidly create vasculature and improve the function of engineered living tissues.

The research was conducted by a team led by postdoctoral fellow Jordan S. Miller and Christopher S. Chen, the Skirkanich Professor of Innovation in the Department of Bioengineering at Penn (CAMB), along with Sangeeta N. Bhatia, Wilson Professor at MIT, and postdoctoral fellow Kelly R. Stevens in Bhatia’s laboratory.

Their work was published in the journal Nature Materials.

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JUNE 26, 2012 - Penn Researchers Show ‘Neural Fingerprints’ of Memory Associations

Researchers have long been interested in discovering the ways that human brains represent thoughts through a complex interplay of electrical signals. Recent improvements in brain recording and statistical methods have given researchers unprecedented insight into the physical processes underlying thoughts.

A new study by University of Pennsylvania and Thomas Jefferson University scientists brings this work one step closer to actual mind reading by using brain recordings to infer the way people organize associations between words in their memories.

Kahana & Manning pic

The research was conducted by professor Michael J. Kahana, PhD (Neuroscience, left) and former graduate student Jeremy R. Manning, PhD (right), a 2011 graduate of the Neuroscience Graduate Group. They collaborated with other members of Kahana’s laboratory, as well as with research faculty at Thomas Jefferson University Hospital.

Their study was published in The Journal of Neuroscience.

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JUNE 18, 2012 - Psoriasis Increases Risk of Diabetes, Penn Study Shows Skin Disease Shares Common Inflammatory Pathway with Metabolic Disorder

Psoriasis is an independent risk for Type 2 Diabetes, according to a new study by researchers with the Perelman School of Medicine at the University of Pennsylvania, with the greatest risk seen in patients with severe psoriasis. Researchers estimate that an additional 115,500 people will develop diabetes each year due to the risk posed by psoriasis above and beyond conventional risk factors. The research is published in the latest issue of the Archives of Dermatology, a JAMA Network publication.

"These data suggest that patients with psoriasis are at increased risk for developing diabetes even if they don't have common risk factors such as obesity," said senior author Joel M. Gelfand, MD, MSCE (Epidemiology and Biostatistics group). "Patients with psoriasis should eat a healthy diet, get regular exercise, and see their physician for routine preventative health screenings such as checks of blood pressure, cholesterol, and blood sugar."

Psoriasis is a common inflammatory skin disease affecting over 7.5 million Americans and causes thick, inflamed, scaly patches of skin. The disease has previously been associated with increased risk of myocardial infarction, stroke, metabolic syndrome and cardiovascular mortality.

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JUNE 6, 2012 - Good Bugs Gone Bad: Microbes that Promote Normal Health Can "Turn Bad" if Found Outside the Intestine

bugsThe healthy human intestine is colonized with over 100 trillion beneficial, or commensal, bacteria of many different species. In healthy people, these bacteria are limited to the intestinal tissues and have a number of helpful properties, including aiding in the digestion of food and promoting a healthy immune system. However, several chronic human diseases, including HIV/AIDS, inflammatory bowel disease, viral hepatitis, and obesity are associated with the spread of these intestinal commensal bacteria to the blood stream and other peripheral tissues, which can cause chronic inflammation.

David Artis, PhD, (Immunology, Cell & Molecular Biology), and Gregory F. Sonnenberg, PhD, a postdoctoral researcher in the Artis lab, have identified that immune cells, called innate lymphoid cells, are resident in the intestinal tissues of healthy humans, mice, and non-human primates, and are critical in limiting the location of commensal bacteria. If the innate lymphoid cells are depleted in mice, commensal bacteria move to peripheral tissues and promote inflammation.

"A fundamental question that has puzzled researchers for many years is how did the human body evolve to accommodate all these commensal bacteria and keep them in their correct locations?," asks Artis. "The indication from these studies is that the body may have many different pathways to limit the spread of commensal bacteria and these pathways may be tailored to specific types of bacteria."

The research was published in the current edition of Science.

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May 30, 2012 - Perelman School of Medicine Selected by National Institutes of Health as a Center of Excellence in Pain Education

CoEPEThe Perelman School of Medicine at the University of Pennsylvania, in collaboration with the University of Pennsylvania School of Nursing and School of Dental Medicine, has been designated a national Center of Excellence in Pain Education (CoEPEs) by the National Institutes of Health (NIH).

"Pain is one of the primary reasons that patients seek medical care," said John T. Farrar, MD, PhD (Epidemiology & Biostatistics group), co-principal investigator of the new center. "Learning how to properly diagnose the underlying cause and how to effectively treat both acute and chronic pain needs to be an important focus of medical education. The interprofessional collaboration between three Penn schools in this endeavor is pivotal to our mission to help redefine pain education in the U.S. health care system and improve the lives of all of our patients."

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May 29, 2012 - T Cells ‘Hunt’ Parasites Like Animal Predators Seek Prey, a Penn Vet-Penn Physics Study Reveals

By pairing an intimate knowledge of immune-system function with a deep understanding of statistical physics, a cross-disciplinary team at the University of Pennsylvania, led by senior authors Christopher Hunter, professor and chair of the Pathobiology Department in Penn’s School of Veterinary Medicine (Cell & Molecular Biology and Immunology Graduate Groups), and Andrea Liu, the Hepburn Professor of Physics in the Department of Physics and Astronomy, has arrived at a surprising finding: T cells use a movement strategy to track down parasites that is similar to strategies that predators such as monkeys, sharks and blue-fin tuna use to hunt their prey.

With this new insight into immune-cell movement patterns, scientists will be able to create more accurate models of immune-system function, which may, in turn, inform novel approaches to combat diseases from cancer to HIV/AIDS to arthritis.

The study, published in the journal Nature, was conducted in mice infected with the parasite Toxoplasma gondii.

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May 17, 2012 - Penn Medicine Research Challenges Concept That Raising HDL Helps Counter Heart-attack Risk

A new study published by researchers at the Perelman School of Medicine at the University of Pennsylvania, the Broad Institute, and Massachusetts General Hospital, challenges the conventional concept that raising a person's HDL levels (good cholesterol) will always help lower their risk of a heart attack. In the study, published in May 17 edition of The Lancet, the research team analyzed previously identified DNA sequence variations directly associated with elevated HDL levels in humans. After analyzing the genes of roughly 170,000 individuals, the team discovered that none of these established genetic variations actually reduced the risk of heart attack.

"The concept that genetic data can directly test the relationship between a biomarker like HDL to heart attack is an extremely potent one. Through our research, we have found that all roads that raise HDL do not always lead to the promise land of reduced risk of heart attack," said Benjamin F. Voight, PhD (PHRM), lead author of the new study. "These data have important implications for future development of therapies based on raising HDL levels."

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May 17, 2012 - Penn Researchers Recognized for Improving Nanotech Design Principles

bpjA team of University of Pennsylvania researchers has recently been recognized by the National Science Foundation for the development of computer models that will be instrumental in improving the design of pharmaceuticals on an atomic scale.

Led by Ravi Radhakrishnan, PhD (BMB, GCB), the team also included Portonovo Ayyaswamy, PhD (Engineering) as well as David Eckmann, PhD, MD, and Vladimir Muzykantov, PhD (PHRM).

The team received a “Research Highlight” from the NSF’s Division of Chemical, Bioengineering, Environmental & Transport Systems, and the work for which they were honored was published in the Biophysical Journal.

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May 1, 2012 - Three Penn Faculty Elected to the National Academy of Sciences

Nancy Bonini, PhD (NGG), Gideon Dreyfuss, PhD (CAMB, BMB), and Beatrice H. Hahn, MD (CAMB), of the University of Pennsylvania have been elected members of the National Academy of Sciences, considered one of the highest honors that can be accorded a U.S. scientist or engineer.

Cited for “their distinguished and continuing achievements in original research,” the three scientists are part of the 2012 Academy class of 84 members and 21 foreign associates.

photos

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April 23, 2012 - Garret Fitzgerald of Penn's Perelman School of Medicine Elected to the Royal Society

FitzgGerald photoGarret FitzGerald, MD (GCB), is among the 44 newly elected Fellows and eight newly elected Foreign Members to the Royal Society.

"Science impacts on most aspects of modern life, improving our understanding of the world and playing an increasing role as we grapple with problems such as feeding a growing global population and keeping an aging population healthy. These scientists who have been elected to the Fellowship of the Royal Society are among the world's finest. They follow in the footsteps of luminaries such as Newton, Darwin and Einstein and I am delighted to welcome them into our ranks," noted Sir Paul Nurse, President of the Royal Society.

"I am deeply honored by this recognition of the efforts and accomplishments of those with whom I have been privileged to work," said FitzGerald.

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April 4, 2012 - Penn Medicine Researchers Find that Molecular Pair Controls Time-Keeping and Fat Metabolism

The 24-hour internal clock controls many aspects of human behavior and physiology, including sleep, blood pressure, and metabolism. Disruption in circadian rhythms leads to increased incidence of many diseases, including metabolic disease and cancer. Each cell of the body has its own internal timing mechanism, which is controlled by proteins that keep one another in check.

One of these proteins, called Rev-erb alpha, was thought to have a subordinate role because the clock runs fairly normally in its absence. New work, published in Genes and Development this month, from the lab of Mitchell Lazar, MD, PhD (CAMB, GCB, PRHM), found that a closely related protein called Rev-erb beta serves as a back-up for Rev-erb alpha. When both are not functioning, the cellular clock loses its time-keeping function.

The two Rev-erbs work together to control fat metabolism, and in their absence, the liver fills with fat. These findings establish the Rev-erbs as major regulators of both clock function and metabolism.

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3/26/2012 - Inner Weapons Against Allergies: Gut Bacteria Control Allergic Diseases, Perelman School of Medicine Study Finds

When poet Walt Whitman wrote that we "contain multitudes," he was speaking metaphorically, but he was correct in the literal sense. Every human being carries over 100 trillion individual bacterial cells within the intestine -- ten times more cells than comprise the body itself.

Now, David Artis, PhD (IMUN, CAMB), along with postdoctoral fellow David Hill, PhD, and collaborators from The Children's Hospital of Philadelphia and institutions in Japan and Germany, have found that these commensal bacteria might play an important role in influencing and controlling allergic inflammation. The commensal relationship that develops between humans and internal bacteria is one in which both humans and bacteria derive benefits.

The study -- appearing this week in Nature Medicine -- suggests that therapeutic targeting of immune cell responses to resident gut bacteria may be beneficial in treating allergic diseases.

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3/23/2012 - Brain Insulin Resistance Contributes to Cognitive Decline in Alzheimer's Disease

faculty photoInsulin resistance in the brain precedes and contributes to cognitive decline above and beyond other known causes of Alzheimer's disease, according to a new study by researchers from Penn's Perelman School of Medicine. This is the first study to directly demonstrate that insulin resistance occurs in the brains of people with Alzheimer's disease. The study is now online in the Journal of Clinical Investigation.

"Our research clearly shows that the brain's ability to respond to insulin, which is important for normal brain function, is going offline at some point...We believe that brain insulin resistance may be an important contributor to the cognitive decline associated with Alzheimer's disease," said senior author, Steven E. Arnold, MD (NGG).

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3/15/2012 - Genetic Variation in Human Gut Viruses Could be Raw Material for Inner Evolution, Perelman School of Medicine Study Finds

faculty photo A growing body of evidence underscores the importance of human gut bacteria in modulating human health, metabolism, and disease. Yet bacteria are only part of the story. Viruses that infect those bacteria also shape who we are. Frederic D. Bushman, PhD (CAMB, GCB), led a study published this month in the Proceedings of the National Academy of Sciences that sequenced the DNA of viruses -- the virome -- present in the gut of healthy people.

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3/9/2012 - Dennis Discher Elected to National Academy Of Engineering

disher photoDennis E. Discher, PhD (CAMB, PHRM), has been elected to the National Academy of Engineering for his accomplishments in "elucidation of the effects of mechanical forces on cell physiology and stem cell development."

Election to the National Academy of Engineering is among the highest professional distinctions accorded to an engineer. Academy membership honors those who have made outstanding contributions to "engineering research, practice, or education, including, where appropriate, significant contributions to the engineering literature," and to the "pioneering of new and developing fields of technology, making major advancements in traditional fields of engineering, or developing/implementing innovative approaches to engineering education."

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2/6/2012 - Molecular Path from Internal Clock to Cells Controlling Rest and Activity Revealed in Penn Study

The molecular pathway that carries time-of-day signals from the body's internal clock to ultimately guide daily behavior is like a black box, says Amita Sehgal, PhD (CAMB, NGG) the John Herr Musser Professor of Neuroscience and Co-Director, Comprehensive Neuroscience Center, at the Perelman School of Medicine, University of Pennsylvania.

Now, new research from the Sehgal lab is taking a peek inside, describing a molecular pathway and its inner parts that connect the well-known clock neurons to cells governing rhythms of rest and activity in fruit flies. Sehgal is also an investigator with the Howard Hughes Medical Institute.

The other co-author on the study is Wenyu Luo, PhD, a CAMB doctoral student who recently defended her dissertation. The findings, which will be featured on the cover of the February 17th issue of Cell, are published online this week.

"Most colleagues would say that we have some understanding of how the clock works and how it is synchronized with light,” says Sehgal. “But we are just beginning to get a glimpse of how the clock drives behavior in the rest of an organism's systems."

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2011

12/23/2011 - Penn Researchers Shorten Time for Manufacturing of Personalized Ovarian Cancer Vaccine

Researchers from the Perelman School of Medicine at the University of Pennsylvania are in the midst of testing a personalized, dendritic cell vaccine in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer – a group of patients who typically have few treatment options. Now, they have shown they can shorten the time to manufacture this type of anti-cancer vaccine, which reduces costs of manufacturing the treatment while still yielding powerful dendritic cells that may be beneficial for these and a variety of other tumor types. The data is published in the December issue of PLoS ONE.

“We are very excited about this development,” says senior author George Coukos, MD, PhD (CAMB, IGG), who directs the Ovarian Cancer Research Center in Penn’s Abramson Cancer Center. “Our work proves that these dendritic cells can be manufactured with a reasonable cost and retain their potency after being loaded with patients’ tumor extract. This is a very personalized approach to immunotherapy, which can be easily prepared for most patients with ovarian cancer undergoing surgery to remove their tumors.”

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12/16/2011 - Penn Scientist Receives Senior Scholar Award from Ellison Medical Foundation for Aging Research

James Eberwine, PhD, (NGG, GCB, PHRM), has received a Senior Scholar Award from the Ellison Medical Foundation. This supports basic biological research in aging, for $600,000 to be disbursed over the next four years. He is one of 20 investigators to receive this award.

“This grant will enable us to use cutting-edge technologies to assess the contribution of protein synthesis in modulating the aging cell phenotype,” says Eberwine. “One of the unique aspects of these studies is our ability to assess translation of multiple RNAs simultaneously in subregions of aging cells.”

The Ellison Senior Scholar program in Aging is designed to support established investigators to conduct research in the basic biological sciences relevant to age-related diseases and disabilities.

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11/16/2011 - Form and Function: New MRI Technique Measures Brain Structure and Function to Diagnose or Rule Out Alzheimer's Disease

On the quest for safe, reliable and accessible tools to accurately diagnose Alzheimer's disease, researchers from the Perelman School of Medicine at the University of Pennsylvania found a new way of diagnosing and tracking Alzheimer's disease, using an innovative magnetic resonance imaging (MRI) technique called Arterial spin labeling (ASL) to measure changes in brain function. The team determined that the ASL-MRI test is a promising alternative to the current standard, a specific PET scan that requires exposure to small amounts of a radioactive glucose analog and costs approximately four-times more than an ASL-MRI. Two studies now appear in Alzheimer's and Dementia: The Journal of the Alzheimer’s Association and Neurology.

In brain tissue, regional blood flow is tightly coupled to regional glucose consumption, which is the fuel the brain uses to function. Increases or decreases in brain function are accompanied by changes in both blood flow and glucose metabolism,” explained John A. Detre, MD, (NGG), senior author on the papers, who has worked on ASL-MRI for the past 20 years. “We designed ASL-MRI to allow cerebral blood flow to be imaged noninvasively and quantitatively using a routine MRI scanner.”

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11/14/2011 - Tip of the Iceberg: Genetic Screening in Yeast Reveals New Candidate Gene for Lou Gehrig's Disease, Penn Study Finds

Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a universally fatal neurodegenerative disease. Mutations in two related proteins, TDP-43 and FUS, cause some forms of ALS. Specifically, these two proteins are RNA-binding proteins that connect to RNA to regulate the translation of proteins and other cellular functions such as RNA splicing and editing. In a new study, researchers at the Perelman School of Medicine at the University of Pennsylvania discovered additional human genes with properties similar to TDP-43 and FUS that might also contribute to ALS.

There are over 200 human RNA-binding proteins, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathology. Using yeast as a model organism, the lab of cell biologist and senior author Aaron Gitler, PhD, (CAMB), surveyed 133 of these proteins. Their findings appear this week in the Proceedings of the National Academy of Sciences.

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11/14/2011 - In a Childhood Cancer, Basic Biology Offers Clues to Better Treatments

By studying tumor biology at the molecular level, researchers are gaining a deeper understanding of drug resistance - and how to avoid it by designing pediatric cancer treatments tailored to specific mutations in a child’s DNA. In a fruitful collaboration, pediatric oncologists and biochemists are targeting neuroblastoma, an often-deadly childhood cancer of the peripheral nervous system.

"This has been a terrific collaboration," said study co-leader Mark A. Lemmon, Ph.D., (BMB, CAMB, PHRM). "We have been working for a long time to understand how growth factor receptors work as signaling 'machines.'"

The study appears in the Nov. 9 issue of Science Translational Medicine. For more information, please see the CHOP release.

 

11/10/2011 - Tales from the Crypt: Penn Study on Gut Cell Regeneration Reconciles Long-Standing Research Controversy

The lining of the intestine regenerates itself every few days as compared to say red blood cells that turn over every four months. The various cell types that do this come from stem cells that reside deep in the inner recesses of the accordion-like folds of the intestines, called villi and crypts.

But exactly where the most important stem cell type is located -- and how to identify it -- has been something of a mystery. In fact, two types of intestinal stem cells have been proposed to exist but the relationship between them has been unclear.

Some researchers have been proponents of one type of stem cell or the other as the "true" intestinal stem cell. Recent work published this week in Science from the lab of Jonathan Epstein, MD, (CAMB) may reconcile this controversy. The findings suggest that these two types of stem cells are related.

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11/02/2011 - Penn Gastroenterologists Collaborate on $8 Million Barrett's Esophagus Translational Research Network

A research group at the Perelman School of Medicine of the University of Pennsylvania, led by John Lynch, MD, PhD, (CAMB) has received a National Cancer Institute grant to establish a Barrett's esophagus translational research network with Columbia University and the Mayo Clinic. Barrett's esophagus is an increasingly prevalent, pre-cancerous disorder that results primarily from reflux of acid and bile. It afflicts millions of Americans and is a precursor to esophageal adenocarcinoma, which has the fastest rate of increase of any cancer in the US.

"We are all very excited to be a part of this multicenter research network," says Lynch. "Our understanding of the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma has lagged behind that of other cancers because we have not yet developed physiologically relevant laboratory models and an integrated research network, both of which are supported by this award."

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10/24/2011 - Penn Study Explains Paradox of Insulin Resistance Genetics

Obesity and insulin resistance are almost inevitably associated with increases in lipid accumulation in the liver, a serious disease that can deteriorate to hepatitis and liver failure. A real paradox in understanding insulin resistance is figuring out why insulin-resistant livers make more fat. Insulin resistance occurs when the body does a poor job of lowering blood sugars.

The signals to make lipid after a meal come from hormones - most notably insulin - and the direct effect of nutrients on the liver. In a recent issue of Cell Metabolism, Morris Birnbaum, MD, PhD (CAMB, BMB), describes the pathway that insulin uses to change the levels of gene expression that control lipid metabolism. Birnbaum is also associate director of the Institute of Diabetes, Obesity, and Metabolism at Penn.

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10/6/2011 - Abnormal Parkinson's Disease Protein Induces Degeneration in Healthy Nerve Cells, Penn Study Finds

Research from the Perelman School of Medicine has found that small amounts of misshapened brain proteins can be taken up by healthy neurons and replicated within them to cause neurodegeneration. Virginia Man-Yee Lee, PhD (CAMB, PHRM, NGG, BMB), director of the Center for Neurodegenerative Disease Research and John H. Ware Professor in Alzheimer's Research, was senior author of the research, which shows a way that Parkinson’s disease (PD) can spread in the brain and provides a model for discovering therapeutics targeting PD neurodegeneration. This research was published in the neuroscience journal Neuron and funded by the National Institutes of Health for the Penn Udall Center, the Picower Foundation, the Jeff Keefer Foundation, the Parkinson Council, and the Stein-Bellet Family Foundation.

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10/5/2011 - Penn Researchers Receive $9 Million NIH Grant to Study Relationship Between Gene Variants and Cardiovascular Disease

Daniel J. Rader, MD (CAMB, PHRM) and Edward Morrisey, PhD (CAMB), along with researchers at the Medical College of Wisconsin, have received a five-year, $9 million grant for stem cell research from the National Institutes of Health’s National Human Genome Research and the National Heart Lung and Blood Institutes.

The funding will be used in a collaborative study between both institutions on the role of genetics in cardiovascular disease. Rader and Morrisey will take fat cells and change them into induced pluripotent stem cells, or iPS cells, which will be turned into liver cells to learn more about the causes of coronary artery disease and metabolic disorders.

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