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    Laura McLane and Mike Betts -Purified human CD8 T-cells were stained with a-T-bet (green), a-Lamin A (pink), and DAPI (blue) and imaged on a multilaser-based spinning disk confocal microscope (Zeiss). T-bet can be localized to both the nuclear and cytoplasmic compartments of specific subsets of human CD8 T-cells.

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    3D image of the inflamed meningeal membrane of a CX3CR1-GFP reporter mouse infected with Toxoplasma gondii. The dura mater that surrounds the brain is blue, blood vessels are labeled red and microglia and macrophages are green. Contributors for image are ChristophKonradt and Chris Hunter.

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    Time series of cells expressing GFP-tagged ebola viral protein VP40, pseudocolored as a fluorescence intensity heatmap. The contributors for image are: Gordon Ruthel, Xiaohong Liu, Ron Harty, and Bruce Freedman.

IFI Members in the News

Progress on HIV/AIDS

July 18, 2014

Ian Frank, MD, professor in the division of Infectious Diseases and director of Anti-Retroviral Clinical Research in the Penn Center for AIDS Research, was a guest on WHYY'ss "Radio Times" with Marty Moss-Coane for a show on the progress of HIV/AIDS treatment and research. Where do we stand in the battle against the epidemic? Frank was joined by AIDS activists for a roundtable discussion—everything from the Mississippi baby to the recent loss of the AIDS researchers on the downed Malaysian flight was tackled. “This is a huge tragedy for everyone that lost their lives and for their families and friends,” said Frank. “This is a huge blow to the HIV community,” he added.

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As pancreas cancer threat grows, so do strategies

July 13, 2014

A war on pancreas cancer is underway right here at the Abramson Cancer Center. A story in Sunday’s Philadelphia Inquirer featured the work of Jeffrey Drebin, MD, chair of Surgery and the John Rhea Barton Professor of Surgery, and Robert Vonderheide, MD, the Hanna Wise Professor in Cancer Research in the ACC. Drebin and Vonderheide—both co-leads on Stand up to Cancer Dream Teams—are investigating new targeted therapies, immunotherapies, and more, to better the understand and treat the disease, which is projected to become this country's second-leading cancer killer. "We absolutely need to figure it out," said Vonderheide. "It's a medical emergency." Ongoing studies at the ACC have shed light on tumor biology and shown success with the antimalarial drug hydroxychloroquine. "We're not declaring victory,” Drebin told the Inquirer. “We're declaring progress.”.

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FDA Designates Penn's Leukemia Treatment as 'Breakthrough Therapy'

July 9, 2014

In continuing coverage, WHYY radio talked to David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in the Abramson Cancer Center, about the recent FDA "Breakthrough Therapy" designation awarded to Penn's immunotherapy to treat relapsed and refractory adult and pediatric acute lymphoblastic leukemia.  The designation--a first for a personalized cellular therapy to treat cancer-- should help expedite the review and approval process. "It allows us to work more collaboratively with the FDA so that the trials can be done efficiently so there can be proper and early oversight," Porter said. "Hopefully, it will be on a more rapid path to approval in the future."

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Penn' s Immunotherapy for Leukemia Receives FDA's Breakthrough Designation

July 7, 2014

The U.S. Food and Drug Administration awarded the University of Pennsylvania’s personalized immunotherapy—known as CTL019—its Breakthrough Therapy Designation for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia (ALL), reports the Wall Street Journal and Reuters. Such a designation expedites the development and review of new medicines that treat serious or life-threatening conditions. “Receiving the FDA’s Breakthrough Designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease,” said Carl June, MD, the Richard W. Vague Professor in Immunotherapy and director of Translational Research in the Abramson Cancer Center. CTL019 is the first personalized cellular therapy for the treatment of cancer to receive this important classification. The announcement was also covered by Agence France-Presse, the Philadelphia Business Journal, and Fierce Biotech.

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Laser and Drones: June at Penn Medicine, in Photos

June 30, 2014

The University of Pennsylvania campus largely falls silent in the summer months, but Penn Medicine keeps on truckin'. In fact, the month of June featured two of my favorite photography assignments thus far: lasers and drones.

First up, we have E. John Wherry, PhD, director of the Institute for Immunology, and his Becton Dickenson LSR II flow cytometer. If you have no idea what that means, you're not alone — so Wherry was kind enough to explain it:

"This instrument allows us to assess up to 20 parameters simultaneously at a single cell level with an amazing rate of up to 20,000 cells/second," he wrote in an e-mail. "As a result we can perform detailed profiling of the function of immune cells in different disease states."

Long story short, it enables researchers to determine which therapies are working and why a given therapy is effective or ineffective. This ultimately helps us develop better therapies and determine which patients will respond to a given treatment.

On top of that, it looks really cool. Wherry popped the hood on it and let me take a few shots. You can see them — and Wherry — in the slideshow at the bottom of this post.

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Penn Immunologist to Co-direct $12 Million Grant to Study Hepatitis

June 30, 2014

John Wherry, PhD, an associate professor of Microbiology in the Perelman School of Medicine at the University of Pennsylvania, and colleagues from Massachusetts General Hospital (MGH) are co-directing a $12 million grant to study immune responses in people who have been effectively cured of hepatitis C viral infection with new, high-potency antiviral drugs.  This grant is part of the Cooperative Centers for Human Immunology program, administered by the National Institute of Allergy and Infectious Diseases.

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Outstanding New Investigator Award

June 19, 2014

IFI investigator, Daniel J. Powell Jr. Ph.D., has been selected by the Board of Directors from the American Society of Gene & Cell Therapy (ASGCT) for a 2014 Outstanding New Investigator Award. Dr. Powell was selected from a competitive field of nominations based upon his significant contributions to the field of gene and cell therapy. The award ceremony and presentation session was held during the 17 th Annual Meeting in Washington DC on May 23 rd , 2014, and was attended by thousands of meeting participants. Below is a summary from his award presentation:

The Powell Lab is developing innovative immunotherapy strategies built upon clinical observations and studies in basic T cell biology. Adoptive T cell therapy using naturally-occurring tumor infiltrating lymphocytes (TILs) or peripheral blood T cells genetically modified to express a chimeric antigen receptor (CAR) can mediate comprehensive cancer elimination in patients, provided that highly avid, tumor antigen-specific T cells with the ability to proliferate and persist after infusion can be identified. We recently overcame one obstacle to widespread TIL therapy by showing that naturally-occurring tumor-reactive T cells in various cancers can be identified by their cell surface expression of the TNFR superfamily receptor, CD137, demonstrating a role for CD137 in the immunobiology of cancer. To instill T cells with enhanced ability to persist after infusion, we recently applied CAR technology as a tool to test the impact of various costimulatory signals on human CAR T cell survival following antigen encounter in vivo, and discovered a functional role for CD27 in human T cell memory formation. We also devised a novel dual CAR T cell approach where the TCR signal is dissociated from costimulatory signals in two independent CARs of distinct antigen specificity, thus delivering tumor-focused activity while comparatively sparing normal healthy tissues expressing a low level of single antigen. Lastly, to develop widespread T cell therapy, we pioneered a universal immune receptor approach that is adaptable in antigen specificity, allowing for highly personalized T cell generation based upon the repertoire of antigens expressed by each individual’s cancer cells. These strategies build on the early success of adoptive immunotherapy by addressing significant hurdles to otherwise safe and effective T cell therapy.

Check Up: Chronic Inflammation's Scourge Effect

June 2, 2014

The Philadelphia Inquirercovered 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.

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"Bystander" Chronic Infectinos Thwart Development of Immue Cell Memory, Penn Study Finds

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.  

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Immune Cells Outsmart Bacterial Infection by Dying, Penn Vet Study Shows

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.

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Healing the Future

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."

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Growing plants to save lives

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.

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Penn Medicine Physician to Co-Lead Stand Up to Cancer "Dream Team" to Fight Pancreatic Cance

April 7, 2014

IFI Faculty Member and Cancer Immunology Program Leader, Robert Vonderheid,e 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.

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Commander of an Immune Flotilla

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.

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Penn Immunology Program Ranks High in the U.S. News list

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

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Cancer Suppressor Gene Links Metabolism with Cellular Aging

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.

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Wistar to Launch Largest Randomized Trial Aiming for an HIV Cure by Diminshing 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.

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Paths Not Taken: Notch Signaling Pathways Keep Immature T Cells on the Right Track

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.”.

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Institute of Medicine Elects IFI Faculty Member

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.

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Delivering Drugs with Plants, Penn's Henry Daniell Aims to Save Lives

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.

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The Sneaky Immunologist

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.

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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.

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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.

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Recent IFI Faculty Awards and Honors

 


Kyong-Mi Chang, M.D.

Appointed Associate Dean for Research at the Philadelphia Veteran Affairs Medical Center (PVAMC)


Greg Sonnenberg, Ph.D.

Nominated to the Forbes 30 Under 30 list in Science and Healthcare


Edward Behrens, M.D.

Recipient of the Stewart J. McCracken Award from the Arthritis Foundation


Carl June, M.D.

Elected into the Institute of Medicine