June 2, 2014
The Philadelphia Inquirer covered research by E. John Wherry, PhD, director of the Institute for Immunology and postdoctoral fellow Erietta Stelekati, PhD, explaining why the immune system is less capable of developing immunity to diseases when it is fighting a background 'bystander' infection. The researchers fingers a key culprit in these breakdowns of the immune system: chronic inflammation. They explain how long-term inflammation from one infection impairs the ability of infection-fighting T cells to form memories of any additional invaders - thereby hampering the immune system's ability to recognize and attack those invaders on future occasions.
May 15, 2014
A team from the Perelman School of Medicine, led by E. John Wherry, director of the Institute for Immunology, found that chronic bystander viral or parasitic infections – which are models for human infections like hepatitis, malaria, and parasitic worms – impaired the development of memory T cells in mouse models of long-term infection. The effect of bystander infections also extended beyond mice. The researchers generated signatures of transcribed genes of cytomegalovirus-specific T cells from people with chronic hepatitis C infection and healthy controls. The gene-expression profiles of these two groups showed a clear impact of bystander chronic infection on T cells, including a difference in expression of many key T-cell memory-related genes.
May 5, 2014
A new study led by Igor Brodsky, an Assistant Professor of Pathobiology at Penn Vet, has painted a clearer picture of the delicate arms race between the human immune system and a pathogen that seeks to infect and kill human cells. The research explores the strategies by which the bacterial pathogen Yersinia, responsible for causing plague and gastrointestinal infections, tries to outsmart immune cell responses and looks at the tactics used by the immune system to fight back.
April 29, 2014
David Porter, M.D., a professor of Medicine and director of Blood and Marrow Transplantation in the Abramson Cancer Center, is quoted in a CNN feature detailing 10 recent medical advances that are saving lives in new ways, including an ACC team's work modifying cancer patients' own immune cells to attack their cancer. "This is absolutely one of the more exciting advances I've seen in cancer therapy in the last 20 years," Porter says. "We've entered into a whole new realm of medicine."
April 10., 2014
Tucked behind old factory buildings on Penn's South Bank campus stands a gleaming greenhouse. The $2 million structure, completed late last year, is state-of-the-art. The greenhouse is the domain of Henry Daniell, a professor in the departments of Biochemistry and pathology at Penn Dentaland director of translational research. Daniell joined Penn's faculty last year and has been working diligently to see his research move from the lab to the clinic. His life's work centers on a unique means of delivering drugs and vaccinations to the human body. Instead of relying upon sterile injections to ferry the therapeutic protein of interest to the intended tissue, Daniell has used a humbler vehicle: lettuce leaves.
April 7, 2014
IFI Faculty Member and Cancer Immunology Program Leader, Robert Vonderheide will be a co-leader on the recently announced Stand Up To Cancer (SU2C)-Lustgarten Foundation Pancreatic Cancer Convergence Dream Team. The new effort, titled “Transforming Pancreatic Cancer to a Treatable Disease,” was announced here today by SU2C and The Lustgarten Foundation, along with the American Association for Cancer Research (AACR), SU2C’s Scientific Partner, at a press event during the AACR Annual Meeting 2014 Armed with $8 million in funding over the course of three years, Dr. Vonderheide and investigators from Penn’ Abramson Cancer Center and several other institutions will work together to develop new therapies to harness patients’ own immune cells to treat pancreatic cancer.
April 1, 2014
An article in The Scientist profiles Carl June, MD, a professor of Pathology and Laboratory Medicine and director of Translational Research in the Abramson Cancer Center. The article traces his career from his years as a Naval physician-scientist specializing in HIV to his recent success leading the Penn research team that has demonstrated success using engineered versions of patients' own immune cells to combat their blood cancers. The article also notes his longtime collaborations with Bruce Levine, PhD, an associate professor of Pathology and Laboratory Medicine and director of the Cell and Vaccine Production Facility, and David Porter, MD, a professor of Medicine and director of Blood and Marrow Transplantation in the Abramson Cancer Center.
March 17, 2014
The Immunology Graduate Group is #6 in the U.S. News & World Report rankings of Best Graduate Schools. According to U.S. News, Penn is one of "the best science schools for immunology/infectious disease." See the U.S. News & World Report website for a list of programs
January 14, 2014
A team of researchers from the Perelman School of Medicine has identified a class of p53 target genes and regulatory molecules that represent more promising therapeutic candidates. As Xiaolu Yagn, PhD Professor of Cancer Biology and his team describe in an advance online Nature publication, p53 particpates in a molecular feedback circuit with malic enzymes, thereby showing that p53 activity is also involved in regulating metabolism.
Wistar to Launch Largest Randomized Trial Aiming for an HIV Cure by Diminishing Viral Reservoir Beyond Current Therapies
January 13, 2014
A multi-institutional research team led by Luis Montaner, D.V.M., D.Phil., a professor at The Wistar Institute and director of Wistar's HIV-1 Immunopathogenesis Laboratory, has received a four-year, $6.2 million grant from the National Institute of Allergy and Infectious Diseases of the National Instiuttes of Health to hold a trial of a new therapeutic strategy that has shown strong signs that it can diminish the amount of persistent HIV-1 virus residing in the cells of people with HIV/AIDS. While current therapies for HIV/AIDS hold the HIV-1 virus at bay, they do not reduce the amountof virus within patients,which is a necessary first step toward a cure.
November 22, 2013
The lab of Avinash Bhandoola, PhD, professor of Pathology and Laboratory Medicine, has studied the origins of T cells for many years. One protein called Notch, which has well-known roles in the development of multiple tissues, plays an essential role in triggering T-cell development. With graduate student Ellen DeObaldia, Bhandoola describes in Nature Immunology how Notch signaling induces gene expression of genes that promote the maturation of T cells and discourage alternative cell fates. Deficiency of the Notch target gene Hes1 in blood stem cells results in extremely low T-cell numbers, but the underlying mechanism is unknown. Keeping in mind that Notch signaling gone awry induces leukemia, De Obaldia notes that “understanding the Notch pathway on a molecular level can shed light on how normal cells are transformed in the context of cancer.”.
October 21, 2013
Seven professors from the Perelman School of Medicine, including IFI faculty member Dr. George Shaw, have been elected members of the Institute of Medicine (IOM), one of the nation's highest honors in biomedicine. Established in 1970 by the National Academy of Sciences, IOM has become recognized as a national resource for independent, scientifically informed analysis and recommendations on health issues. With their election, members make a commitment to volunteer their service on IOM committees, boards, and other activities. George M. Shaw, M.D., Ph.D., is professor of Medicine and Microbiology. His investigative work focuses on the transmission and immunopathogenesis of HIV-1 and hepatitis C virus (HCV), human pathogens that infect more than 200 million individuals worldwide. Shaw is recognized for having developed the first molecular clones of HIV-1, which led to the development of antibody and nucleic acid tests to protect the blood supply and diagnose and monitor HIV-1 infections.
September 3, 2013
An admonishment to eat your greens may take on a whole new meaning if Henry Daniell, who recently joined the faculty of the Penn Dental Medicine, has anything to do with it.His outside-the-box thinking has turned lettuce leaves into drug-delivery systems, with results that have the potential to make disease treatment and prevention affordable to a global population. Now at Penn, Daniell is working to take his plant-based medicine platform from the lab to the clinic, and to begin saving lives.
May 15, 2013
Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn’s Abramson Cancer Center, was named to Fast Company magazine’s list of the Top 100 Most Creative People in Business for 2013. Ranked #11, June leads a team whose work using a gene therapy technique that showing unprecedented results in destroying cancer cells in adult and pediatric patients with leukemias that don't respond to standard therapies. The modified versions of patients' own immune cells creates “ a new army that is trained to attack leukemia on sight” if patients’ cancers recur.
Gregory Sonnenberg: Cellular Spy
May 1, 2013
Growing up outside of Buffalo, New York, Gregory Sonnenberg liked to catch tadpoles and watch them develop in glass jars. “It wasn’t always successful,” he admits. “There was a lot of trial and error.” But that early interest in experimental biology metamorphosed into something more serious, and in 2003 Sonnenberg started college at the State University of New York at Buffalo to study biomedical science.
Penn's Carl June wins Philadelphia Award
April 1, 2013
University of Pennsylvania researcher Carl H. June has been selected to receive the 2012 Philadelphia Award for “his extraordinary advancements in gene therapy aimed at treating HIV and cancer.” June and his team recentlyreported that of the first 12 patients treated with the experimental therapy, nine – including two children – had complete or partial remissions from advanced, intractable leukemia. Two adults remain cancer-free two and a half years after treatment.
February 21, 2013
The body's immune system exists to identify and destroy foreign objects whether they are bacteria, viruses, flecks of dirt or slpinters. Unfortunately, nanoparticles designed to deliver drugs, and implanted devices like pacemakers or artificial joints, are just as foreign and subject to the same response. Now researcher, Dennis Discher, has figured out a way to provide a "passport" for such therapeutic devices, enabling them to get past the body's security system.
December 26, 2102
Gregory Sonnenberg, Ph.D., research associate in the Division of Gastroenterology and the Institute for Immunology was chosen for Forbes magazine's second year of publihing a list of the top-30 rising stars in science and health under the age of 30. His work was described as studying why the immune system sometimes overreacts to "good" bacteria in the intestinal tract, potentially leading to cancer or inflammatory bowel disease. "I was extremely surprised and excited to be nominated to the Forbes 30 Under 30 list in Science and Healthcare," says Sonnenberg. "It is an enormous honor to be named on this list with so many talented scientist and innovators from around the world."
Microbiologist to Lead Penn Medicine's Institute for Immunology
December 18, 2012
E. John Wherry, associate professor of Microbiology, has been named the new Director of the Institute for Immunology (IFI), at the Perelman School of Medicine, University of Pennsylvania. The Penn Institute for Immunology was established in
2009 to provide an administrative and programmatic structure to unify the basic, translational, and clinical immunology communities across the University. The Institute’s primary mission is to establish new interactions and synergistic collaborations that will accelerate innovative discoveries and to apply findings within the basic sciences to clinically–translatable approaches. Its membership now includes more than 160 faculty members from 23 departments across five schools as well as representation from CHOP and the Wistar Institute.
“The Institute for Immunology at Penn is designed to capitalize on our strengths in the basic and translational immunology of inflammation, autoimmunity, cancer, transplantation and infection and to catalyze the next steps in basic science discovery, translational research and clinical treatment of immune-related diseases,” says Wherry. “The IFI will foster cross–disciplinary interactions with other centers and institutes to keep Penn at the forefront of immunology research and treatment.”
Institute for Immunology faculty members Robert Vonderheide, MD and Carl June, MD have been appointed to the editorial board of a new journal, Cancer Immunology Research (CIR). Dr. Vonderheide has been appointed Deputy Editor and Dr. June has been named Senior Editor of the new publication. Cancer Immunology Research plans to publish outstanding original articles reporting major advances in cancer immunology that span the discipline from basic investigations in host–tumor interactions to developmental therapeutics in model systems, early translational studies in patients, and late–stage clinical trials. The journal’s special features will include “Masters of Immunology”—primers by leading immunologists—and “Cancer Immunology at the Crossroads”—perspectives that highlight the intersection of immunology with other areas of cancer research and allied disciplines.
Leukemia Patients Remain in Remission More Than Two Years After Receiving Genetically Engineered T Cell Therapy
December 9, 2012
Nine of twelve leukemia patients who received infusions of their own T cells after the cells had been genetically engineered to attack the patients’ tumors responded to the therapy, which was pioneered by scientists in the Perelman School of Medicine at the University of Pennsylvania. Penn Medicine researchers will present the latest results of the trial today at the American Society of Hematology’s Annual Meeting and Exposition. The clinical trial participants, all of whom had advanced cancers, included 10 adult patients with chronic lymphocytic leukemia treated at the Hospital of the University of Pennsylvania (HUP) and two children with acute lymphoblastic leukemia treated at the Children’s Hopsital of Philadelphia. Two of the first three patients treated with the protocol at HUP remain healthy and in full remissions more than two years after their treatment, with the engineered cells still circulating in their bodies. The findings reveal the first successful and sustained demonstration of the use of gene transfer therapy to turn the body’s own immune cells into weapons aimed at cancerous tumors.
November 29, 2012
When you get an acute infection, such as influenza, the body generally responds with a coordinated response of immune-cell proliferation and attack that rapidly clears the pathogen. Then, their mission done, the immune system stands down, leaving a population of sentinel memory cells to rapidly redeploy the immune system in the event of reinfection. But what about chronic infection? In the case of such pathogens as hepatitis C, HIV, and malaria, the body and the pathogen essentially fight to a prolonged stalemate, neither able to gain an advantage. Over time, however, the cells become “exhausted” and the immune system can collapse, giving the pathogen the edge. Now, a new study by researchers at the Perelman School of Medicine, University of Pennsylvania is showing just how that happens. The findings also suggest a novel therapeutical approach that might be used to shift the balance of power in chronic infections. The study appears in the November 30 issues of Science. The team, led by E. John Wherry, PhD, associate professor of Microbiology and Director of the Institute for Immunology, used a mouse model of chronic viral infection to map the T-cell response that arises when the immune system is on an extended war footing.
October 15, 2012
Six professors from the University of Pennsylvania, representing four schools, have been elected members of the Institute of Medicine (IOM), one of the nation’s highest honors in biomedicine. Established in 1970 by the National Academy of Sciences, IOM has become recognized as a national resource for independent, scientifically informed analysis and recommendations on health issues. The new Penn IOM members include Carl June, the Richard W. Vague Professor in Immunotherapy, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, and the Program Director of Translational Research, Abramson Family Cancer Research Institute.
October 4, 2012
Just 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. Sonnenberg is one of 14 early–career scientists supported this year with an EIA, part of the second annual cohort of awardees.
Septemer 28, 2012
A new study led by University of Pennsylvania researchers has now identified a crucial signaling molecule involved in counterbalancing the immune system attack. “The immune response is like driving a car,” said Christopher Hunter, professor and chair in the Department of Pathobiology in Penn’s School of Veterinary Medicine. “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 research to characterize this immune system “brake” was led by Hunter and Aisling O’Hara Hall, a doctoral candidate in the Immunology Graduate Group.
Good Bugs Gone Bad: Microbes that Promote Normal Health Can “Turn Bad” if Found Outside the Intestine
June 6, 2012
The 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, when it comes to commensal bacteria, location is key. While commensal bacteria in the intestine provide positive effects, 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. ‘Good bugs’ that promote normal health can ‘turn bad’ if found in the wrong location. Now, David Artis, Ph.D., associate professor of Microbiology and Gregory F. Sonnenberg, Ph.D., 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.
May 29, 2012
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 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.
Inner Weapons Against Allergies: Gut Bacteria Control Allergic Diseases, Perelman School of Medicine Study Finds
March 26, 2012
David Artis, Ph.D., Associate professor of Microbiology, along with postdoctoral fellow David Hill, Ph.D., from the Perelman School of Medicine, 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.
November 28, 2011
Medical researchers are again in pursuit of a goal they had all but abandoned: curing AIDS. Until recently, the possibility seemed little more than wishful thinking. But the experiences of two patients now suggest to many scientists that it may be achievable. One man, the so–called Berlin patient, apparently has cleared his H.I.V. infection, albeit by arduous bone marrow transplants.
September 12, 2011
A year ago, when chemotherapy stopped working against his leukemia, William Ludwig signed up to be the first patient treated in a bold experiment at the University of Pennsylvania. Mr. Ludwig, then 65, a retired corrections officer from Bridgeton, N.J., felt his life draining away and thought he had nothing to lose. Special cell–culturing techniques may have contributed to the lab’s success. Doctors removed a billion of his T–cells — a type of white blood cell that fights viruses and tumors — and gave them new genes that would program the cells to attack his cancer. Then the altered cells were dripped back into Mr. Ludwig’s veins. At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst. A few weeks later, the fevers were gone. And so was the leukemia.
September 12, 2011
Doctors have treated only three leukemia patients, but the sensational results from a single shot could be one of the most significant advances in cancer research in decades. And it almost never happened.In the research published Wednesday,doctors at the University of Pennsylvania say the treatment made the most common type of leukemia completely disappear in two of the patients and reduced it by 70 percent in the third. In each of the patients as much as five pounds of cancerous tissue completely melted away in a few weeks, and a year later it is still gone. The results of the preliminary test “exceeded our wildest expectations,” says immunologist Dr. Carl June a member of the Abramson Cancer Center&rsqou;s research team.
July 13, 2011
Targeted therapies that are designed to suppress the formation of new blood vessels in tumors, such as Avastin (bevacizumab), have slowed cancer growth in some patients. However, they have not produced the dramatic responses researchers initially thought they might. Now, research from the Perelman School of Medicine at the University of Pennsylvania might help to explain the modest responses. The discovery, published in the July 14 issue of Nature, suggests novel treatment combinations that could boost the power of therapies based on slowing blood vessel growth (angiogenesis). The Penn investigators, led by George Coukos, MD, PhD, Celso–Ramon Garcia Professor of Reproductive Biology, found that ovarian cancer cells grown under low oxygen conditions—which promote blood vessel formation—secrete chemical signals that suppress the patient’s immune system, preventing it from killing off the abnormal cancer cells.
May 10, 2011
The University of Pennsylvania has received a $225 million gift, the largest in its history, from Raymond G. Perelman and his wife, Ruth, for its medical school, which will be renamed the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania. Amy Gutmann, the president of the university, said the Perelmans’ gift was transformational. “It’s the triple crown for our school of medicine,” she said. “It’s going to enable us to have the best students, with enormously increased financial aid, and to recruit the most eminent faculty and provide extraordinary research.”
March 25, 2011
Sometimes in science, what you get wrong can be just as important as what you get right. Researchers at the University of Pennsylvania Perelman School of Medicine set out two years ago to prove that a new drug could marshal T cells, key players in the immune system, against pancreatic cancer. That didn&rsqou;t happen. Instead, the experimental antibody turned more primitive immune-system cells that often get co–opted into helping pancreatic cancer tumors against part of the tumor structure. Tumors shrank substantially in some patients, and median survival time lengthened by two months, to 7.4 months. That doesn&rsqou;t sound like much, but, with a notoriously deadly cancer, it was a step forward.
March 3, 2011
In a feat that is renewing hopes for conquering AIDS, researchers have genetically engineered patients’ vital immune cells to make them resistant to HIV infection. To confer this invulnerability, scientists took the immune cells from HIV–positive patients’ own blood, then snipped out a single gene—the first time such a precise alteration has been achieved on a meaningful scale. When put back in the patient, the cells no longer make a receptor that HIV needs to enter the cell, effectively blocking the virus.
February 17, 2011
For years, Madlyn and Leonard Abramson have given millions of dollars to fund cancer research at Penn Medicine, including the naming of the Abramsom Cancer Center and the establishment of the Abramson Family Cancer Research Institute. Penn Medicine’s largest donors have given $25.5 million more to support basic science and translational research progress in the Abramson Family Cancer Research Institute, which is among the nation’s preeminent incubators for drug discovery and development of new ways to diagnose and treat patients.
Feburary 4, 2011
So-called barrier sites—the skin, gut, lungs—limit the inner body’s exposure to allergens, pollutants, viruses, bacteria, and parasites. Understanding how the immune system works in these external surfaces has implications for understanding such inflammatory diseases as asthma, psoriasis, IBD, and food allergies, all of which occur at the body’s barriers. David Artis, Ph.D., professor of Microbiology and Gregory F. Sonnenberg, a predoctoral fellow in the Artis lab, have identified an immune cell population that acts as the body’s border patrol with the outside world. They discovered that these lymphoid tissue inducer cells maintain immunity in the intestine of mice. The research appeared in the most recent online issue of Immunity.
Penn Scientists Identify New Role for Protein Molecule That Inhibits Response of Immune-System Cells
November 7, 2010
An international group of scientists, with lead researchers in Penn’s School of Veterinary Medicine and School of Medicine, has shown the unique ability of a protein subunit called IL-27p28 to bind with a key cell receptor (gp130), effectively preventing it from transmitting signals necessary for triggering an immune response. Regulating the production of the molecule could lead to new, targeted interventions for cancer, asthma, lupus, multiple sclerosis, arthritis and other diseases. “Lots of pharmaceutical companies are focused on possible targets upstream or downstream of this key receptor,” said Christopher Hunter, professor and chair of pathobiology in Penn Vet. “Here, we’ve discovered a natural molecule that limits signaling through that receptor. There’s already genetic data out there saying this protein is important in human medicine. We agree with that, but maybe it works a different way than we thought before. Then, having this information means that this natural molecule provides a new way to manage different types of inflammatory diseases.”
October 27, 2010
A recently identified immune cell that directs other cells to fight infection plays a critical role in regulating the immune system in both health and disease. Researchers from the University of Pennsylvania School of Medicine have discovered how a stimulatory molecule and a protein found on the membrane of another immune cell make T helper 17 cells multi–taskers of sorts. Th17 cells protect the body against infection and cancer, but are also culprits in some autoimmune diseases and out–of–control, cancerous cell growth. This new understanding that Th17 cells manage to play both sides of the fence suggests that targeting or inhibiting the involved protein pathways might be a new way to treat cancer, chronic infection, and some autoimmune diseases. Previous studies have linked excessive amounts of Th17 cells in the body to such autoimmune diseases as multiple sclerosis, psoriasis, rheumatoid arthritis, and Crohn’s disease.