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Science: Biomedical or 125 Years


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2017 ANNUAL REPORT

Contents From The President & CEO

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Science Features

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Spotlight On...

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Research Highlights

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Scientific Symposia

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Partners In Discovery

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Foundation Engagement

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Education

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Faculty Developments

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Shared Resources

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Administration & Faculty

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Board of Trustees

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Leadership Council & Ambassadors

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Annual Giving

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Heritage Society

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Wistar Family Gifts

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Community Engagement & Special Events

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2017 Institute Financials

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ON THE COVER

An evolution of The Wistar Institute over the past 125 years. See a full timeline on our website: wista.org/timeline


THEN

1892 The Wistar Institute of Anatomy and Biology was founded in 1892. In addition to housing the Wistar Museum, the Institute was devoted to “any other work for the increase of original scientific knowledge.� As such, Wistar is one of the birthplaces of biomedical research in America and it has been a pioneer in cancer research and vaccine development.

1 2 5 TH A N N I V E R S A R Y

2017 125 years later, Wistar continues to be a world-renowned biomedical research institute at the forefront of cancer and infectious disease research and vaccine development, with state-of-the-art facilities and an internationally recognized faculty.


From the President & CEO DARIO C. ALTIERI, M.D. President & CEO Director, The Wistar Institute Cancer Center Robert and Penny Fox Distinguished Professor

Running Forward At Wistar, we often say that science is a marathon, not a sprint— meaning that scientific success, innovative thinking and research excellence are not the business of instant gratification. Scientific breakthroughs do not happen overnight. There may be luck, but there is no “lucky strike” in science. Instead, the business of science combines seemingly opposite traits of our personas: patience and urgency; resilience and creativity; willingness to take risks but being able to recognize a dead end; courage to accept our mistakes, but curiosity to keep going (especially when things in the lab just don’t seem to make sense… that’s when the real fun starts). Not uncommonly, it takes years for all of it to come together. But when it does, the thrill is palpable, the excitement of novelty is contagious, and the fulfillment of making a contribution that may last forever is incomparable. It makes all the trials and tribulations fade in the distance and readies us for more. These are the sentiments that best describe Wistar during the past year, another innovative Wistar year. In 2017, we witnessed the recruitment of outstanding talents, expansive modernization of our infrastructure and the creation of new, state-of-the-art technological capabilities in core facilities. Staying true to our mission of making Wistar the best place to do research, we have continued to invest in the science, incentivized innovation and creativity, expanded our growing intellectual property portfolio of new therapeutic, diagnostic and vaccine assets, and created philanthropic accelerator mechanisms designed to quickly move research

discoveries from the lab bench to the clinic. We have competed, and succeeded, at all levels. Despite the challenging times with federal funding, our grant portfolio has continued to grow, and our publications have appeared in the most prestigious and impactful scientific literature. Our educational mission to train and develop the next generation of scientists has reached new heights, instilling the excitement of research and discovery from high school students to post-graduate researchers. Importantly, we continue to fulfill our promise to be a beacon of collaboration and scientific synergy. We endeavor to foster creative collaborations with all other academic organizations in the region and throughout the world and with many partners in the biotechnology and pharmaceutical industry. But if science is a marathon, is there a finish line? And is there a finish line for Wistar? How many more transformative Wistar years can there be? The answers to these questions are simple, and ones that we bask in every day. There may be many finish lines, but there is no one finish line—not for our laboratories and not for Wistar as our community. Our quest for knowledge continues unabated, our scientific curiosity is insatiable, and the drive to contribute, to make a difference is a way of life. These are the values that animate Wistar, that make us who we are, what we are recognized for around our neighborhood and around the world. We gain strength from our rich accomplishments of the past for having crossed many finish lines. But it is the future that we embrace with anticipation and confidence.

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S C I E N C E F E AT U R E S

Illustration of Zika virus.

Making Great Strides in the Advancement of Synthetic DNA Technology for Immunotherapy 2017 was a prolific year for the lab of David B. Weiner, Ph.D., executive vice president of The Wistar Institute and director of Wistar’s Vaccine & Immunotherapy Center, marking important advancements in the synthetic DNA technologies under development by the team and their collaborators as novel immunotherapeutic approaches for cancer and infectious diseases. The research conducted by the Weiner Lab aims at creating or boosting the natural immune response providing genetic “instructions” to the host on what to react against or how to develop the necessary and specific antibodies for protection or treatment of disease.

A DNA VACCINE HOLDS PROMISE AGAINST ZIKA DNA vaccines consist of a synthetic genetic sequence that encodes a specific antigen, or a protein from the infectious agent or cancer cell, against which we want the immune system to respond. The synthetic DNA sequence is delivered into the host’s

muscle, skin or local tissue, where it’s used as a blueprint to produce the designed antigen and present it to local immune cells. This triggers a cascade of events culminating in a full-spectrum immune response so that the body will be prepared to attack and destroy any invader expressing the same antigen, be it an infectious agent or a cancer cell. The results of a clinical study conducted in collaboration with the Perelman School of Medicine at the University of Pennsylvania, Inovio Pharmaceuticals, Inc. (Inovio), and GeneOne Life Science, Inc., were published in the prestigious New England Journal of Medicine. Weiner and colleagues evaluated the safety and immunogenicity of the world’s first Zika vaccine. This DNA vaccine against Zika virus was developed by Kar Muthumani, Ph.D., assistant professor in the Vaccine & Immunotherapy Center, together with the Weiner team and outside collaborators, and had been shown effective in preclinical models just a few months earlier.

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“Synthetic DNA vaccines are an ideal approach for emerging infectious diseases like Zika.” —David B. Weiner, Ph.D.

The Zika clinical study represents a milestone because it is the first phase 1 clinical trial for a Zika vaccine and displays the advantages of synthetic DNA technology for pandemic outbreaks. The vaccine can produce an immune response against the virus with high potency and minimal adverse effects. Two groups of 20 participants received two different doses of the vaccine candidate intradermally. Each dosage was followed by the delivery of small, directional electric currents into the skin at the site of injection to facilitate optimal vaccine uptake. Results showed that the vaccine was well-tolerated and effective at driving immune responses that may be associated with protection from Zika infection. “Synthetic DNA vaccines are an ideal approach for emerging infectious diseases like Zika,” said Weiner. “They can be designed and manufactured rapidly, are highly predictable for the generation of immunity in humans, and have significant conceptual safety advantages, and are much more stable than most traditional vaccines, making them exceptionally practical to distribute during outbreaks.”

IMPLICATIONS OF DNA VACCINES FOR CANCER IMMUNOTHERAPY The Weiner team is applying the synthetic DNA vaccine technology to cancer immunotherapy. In a study conducted in collaboration with Inovio, they applied molecular design tools to devise a novel DNA vaccine approach targeting one of the most important cancer antigen targets, called Wilm’s tumor gene 1 (WT1). Results were published in the journal Molecular Therapy. The recent identification of tumor-associated antigens, or proteins that are specifically expressed by tumor cells and not by normal cells, has sparked the development of DNA vaccine approaches against some of these promising targets. Unfortunately, vaccine approaches against WT1 developed by other research teams so far have not appeared promising due to poor immune responses against cancers expressing WT1. Weiner and colleagues used a strategically modified DNA sequence that tags WT1 as foreign to the host immune system,

breaking immune tolerance and improving the immune response. “This is an important time in the advancement of anticancer immunotherapy approaches,” commented Weiner. “The team has developed an approach that may help generate improved immunity to WT1-expressing cancers and may have broader implications for cancer immunotherapy vaccines in general.” The tumor microenvironment protects cancer cells from the host immune system, presenting a major obstacle for the success of cancer immunotherapy, which traditionally targets only the cancer cells. Research from the Weiner team, published in Clinical Cancer Research, demonstrated that combined strategies focusing on the tumor and the tumor microenvironment increase the impact of immunotherapy approaches. They illustrated a synthetic DNA vaccine targeting fibroblast activation protein (FAP), an important target protein that is absent in most normal tissues and highly expressed in the tumor microenvironment, in particular on cancer-associated fibroblasts (CAFs) that are known to promote tumor immune evasion. Weiner and colleagues used the synthetic consensus (SynCon) strategy, previously developed by their team, to design a DNA vaccine in which the FAP gene sequence is modified to render it more visible to the immune system, allowing for improved immune recognition. The team evaluated the therapeutic efficacy of the FAP vaccine in combination with other DNA vaccines targeting tumor cell antigens in mouse models of lung and prostate tumors. Combined immunization generated a more robust antitumor activity, extended tumor control and improved mouse survival compared to either immunotherapy alone. “The strategy we described provides a double-fist punch for targeting difficult cancers,” said Weiner. The DNA vaccine technology for cancer immunotherapy is currently being tested in clinical studies, either as single antigen immunotherapy or with multiple antigens targeted simultaneously. Synthetic DNA vaccines are also being tested in combination with immune checkpoint inhibitors to further enhance their effectiveness.

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S C I E N C E F E AT U R E S

“This is an important time in the advancement of anticancer immunotherapy approaches.” —David B. Weiner, Ph.D.

THE NEW FRONTIER OF ANTIBODY THERAPY FOR THE FLU Creating an effective influenza vaccine is challenging because influenza strains vary each year. Seasonal vaccines are developed against strains that are identified each spring in sentinel laboratories. Vaccines must then be rushed into production to have stock available at the end of the summer when flu season starts. “The matching process is not a perfect science. In some flu seasons, the vaccine available in the fall is not a good match for the circulating virus strains and is less effective,” said Weiner. “Flu occasionally can also shift strains dramatically resulting in a pandemic strain that leaves the population at risk of major health consequences. Furthermore, some vulnerable populations may not respond well to vaccines.” Passive immunization using antibodies is a possible alternative. Antibodies are proteins that bind to antigens present on infected cells and cancer cells. Antibodies can recruit other parts of the immune system to destroy the cells containing the antigen. Monoclonal antibodies are laboratory-produced antibodies engineered to bind specifically to only one antigen and help the immune system fight against infection. The Weiner Lab reported on a novel, simple, passive immunization strategy based on designed synthetic DNA. DNA encoded monoclonal antibodies (DMAbs) are optimized protective antibody molecules produced in vivo by muscle cells following instructions delivered through a DNA molecule. This strategy circumvents the challenges related to production, cost formulation and therapeutic delivery of monoclonal antibodies. The process entirely circumvents the prior requirement for vaccination and may have unique applications in many diverse populations. DMAbs showed promise against a diverse range of influenza viruses. In a study published in npj Vaccines, the Weiner Lab with collaborators at Inovio and MedImmune, the global biologics research and development arm of AstraZeneca, described construction, development, and in vivo delivery of DMAbs encoding optimized influenza-specific antibodies that target influenza A and influenza B viruses. Data obtained in mouse models indicated that delivery of the influenza-targeted DMAbs results in robust expression of functional antibodies that protect mice against lethal doses of different, highly diverse, clinically relevant influenza viruses. Another project the Weiner team, Medimmune and Inovio are collaborating on is applying DMAb technology for generation of protection against antibiotic-resistant bacterial infection. Antibiotic-resistant Pseudomonas aeruginosa is a frequent cause of pneumonia and skin infections in immunocompromised individuals and people with cystic fibrosis, lung transplants and chronic obstructive pulmonary disease, and it is a leading cause of hospital-acquired infections. In Nature Communications, the team demonstrated that delivery of DMAbs in a preclinical model of pneumonia caused by P. aeruginosa lung infection enabled mice to directly produce their own protective antibacterial antibodies.

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David Weiner, Ph.D., discussing an experiment with Sarah Elliott, Ph.D.(left) and Ami Patel, Ph.D (right).

“More than 2 million cases of antibiotic-resistant infections are reported each year in the United States alone, imparting a significant global health and economic burden,” commented Weiner. “This study provides a potential novel approach to further explore for the treatment of bacterial infections.”

DMABS FOR CANCER IMMUNOTHERAPY The therapeutic and prophylactic potential of DMAbs is being extended from infectious diseases to cancer. The first application of this technology to cancer immunotherapy was a study led by Muthumani and Weiner, targeting prostate cancer. Monoclonal antibodies have been explored to target a protein present on the surface of prostate cancer cells called prostate specific membrane antigen (PSMA). Although promising, this strategy is limited by the production cost required to make

these therapeutic antibodies. Additionally, multiple infusions are often required to achieve efficacy. The team engineered DMAbs to make the desired anti-PSMA antibody and tested them in mice for the ability to target human PSMA as well as PSMA-positive tumors. Results showed that antibodies bound to the cancer cells recruited specific immune cells called natural killer cells, resulting in shrinkage of the tumor and significant improvement of survival. The research appeared in the journal Cancer Immunology, Immunotherapy. “This is an important demonstration of the possibilities opened up for immunotherapy by DMAb technology to direct in vivo production of antibodies of major relevance to target and ablate specific tumors,” Weiner said. “More work in this area will be important to understand the applications and limits of this new tool.”

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S C I E N C E F E AT U R E S

Immunofluorescence photograph of a melanoma spheroid.

More Than Skin Deep: Uncovering New Research in Melanoma

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or more than four decades, Meenhard Herlyn, D.V.M., D.Sc., professor and director of The Wistar Institute Melanoma Research Center, has contributed significantly to our scientific understanding of melanoma, the most aggressive form of skin cancer. Herlyn and his lab continued to make important discoveries into therapy resistance and metastasis. In a study published in Nature, the Herlyn Lab and colleagues at the University of Pennsylvania described how melanoma signaling pathways allow the cells to escape therapy, in particular the combination of two targeted therapies—called BRAF and MEK inhibitors. This combination has proven effective but the therapeutic effect is temporary and almost all patients on the regimen eventually relapse. Herlyn and colleagues examined cell lines and tumor biopsies from melanoma patients before and after either BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy. In cell lines and patient samples that developed resistance to the combination therapy, the researchers observed that the pathway governed by an enzyme callled PAK was energized. They also found that treating cells resistant to combination therapy with a PAK inhibitor reduced their ability to grow.

“When cancer gets smart, we have to act even smarter,” said Herlyn. In a separate multi-institutional collaborative study, the Herlyn Lab and scientists at the Medical University of Vienna, Austria, identified the role of tumor-infiltrating or tumor-associated B-cells (“TABs”) in melanoma progression and resistance to targeted therapy. This study provides a molecular mechanism that governs the cross-talk between TABs and tumor cells as well as a potential new therapeutic strategy for combating tumors resistant to treatment. In this study, published in Nature Communications, the scientists described how TABs, which account for up to one third of all immune cells that infiltrate the tumor, can promote tumor cell properties that are associated with drug resistance. “Our results point to an important cancer-promoting function of TABs and elucidate the molecular ‘conversation’ between B cells and melanoma cells, which eventually favors tumor progression and therapy resistance,” Herlyn said. Using a co-culture system of melanoma cells and B cells, Herlyn and team identified those inflammatory factors produced by B cells and melanoma cells that were relevant for the

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“When cancer gets smart, we have to act even smarter.” —Meenhard Herlyn, D.V.M., D.Sc.

interaction and can be used as potential targets for novel therapy, including insulin like growth factor (IGF)-1 and fibroblast growth factor receptor (FGFR)-3. The Herlyn Lab is also focused on understanding how melanoma is able to metastasize. In a study published in Oncogene, they identified a slowly proliferating and highly invasive melanoma cell subpopulation, characterized by production of a protein associated with invasive behavior. The pattern of metastatic dissemination in advanced melanoma is unpredictable because of the biological and genetic diversity that characterizes melanoma cells. The Herlyn Lab has previously shown the existence of a slowly proliferating population of melanoma cells that is required for tumor maintenance. In this new study, they characterized the invasive properties of this population, demonstrating its ability to leave the primary tumor and disseminate rapidly to distant sites. Through proteomic analysis, they found that the slowly proliferating cells express higher levels of the protein SerpinE2, which has a pro-invasive role in other types of cancer. SerpinE2 is also critical for melanoma invasion and its expression levels in melanoma patients correlate with tumor progression. “This concept may sound counterintuitive because we are used to the idea that cancer cells are highly proliferative,” Herlyn said. “However, slowly proliferating melanoma cells are more aggressive and therefore the most dangerous ones.”

Herlyn and his team discussing experiments in the lab.

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S C I E N C E F E AT U R E S

Immune Response to Cancer: When the Immune System Plays for the Enemy

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hile the immune system plays a critical role at keeping cancer at bay, researchers have come to understand all the ways in which cancer can manipulate and bypass the immune system and promote the growth and spread of tumors. Dmitry I. Gabrilovich, M.D., Ph.D., Christopher M. Davis Professor and program leader of Wistar’s Immunology, Microenvironment & Metastasis Program, is a world-renowned leader in this field of research. His work focuses on understanding the role of the tumor microenvironment—the surrounding environment of cells and blood vessels around a tumor—and how it regulates the immune system’s response to cancer. In 2017, the Gabrilovich Lab led three studies that demonstrated just how influential this interplay between the tumor, its microenvironment, and the associated immune response can be when it comes to making sure that new treatments for cancer are effective at targeting the tumor. In collaboration with Indiana University Melvin & Bren Simon Cancer Center and Syndax Pharmaceuticals, Inc., Gabrilovich and his lab demonstrated that a drug called entinostat enhances the antitumor effect of PD-1 (programmed death receptor-1) blockade by inhibiting myeloid derived suppressor cells (MDSCs). MDSCs are a highly immunosuppressive population of tumor infiltrating immature myeloid cells. The combination of entinostat with an anti-PD-1 therapy enhanced T cell-mediated antitumor response, potentially providing an effective combination treatment approach for patients with solid tumors, including lung and renal cell carcinoma. This research was published in Clinical Cancer Research. In another study, Gabrilovich and colleagues discovered a novel form of crosstalk between tumor cells and other types of cells in the tumor microenvironment. These findings formed the basis of a possible immunotherapeutic strategy that inhibits an immune cell population called tumor-associated macrophages (TAMs). TAMs promote tumor cell proliferation and invasion and inhibit antitumor response mediated by T cells. Other researchers have attempted inhibition of the CSF1 receptor as a way of eliminating TAMs, but did not achieve the expected antitumor effects. The Gabrilovich Lab showed that inhibiting the CSF-1 receptor resulted in the unexpected recruitment of polymorphonuclear myeloid-derived suppressor

Illustration of immune cells attacking a cancer cell.

cells (PMN-MDSCs), which favor tumor progression and mediate resistance to immunotherapy approaches. This is mediated by increased production of signaling proteins responsible for attracting PMN-MDSCs in response to CSF-1R inhibition. Therefore, combining inhibitors of CSF-1R with a selective inhibitor of CXCR2 — the receptor of these molecules whose levels are increased, resulted in significant reduction of tumor growth. When both therapies were combined with an immune checkpoint inhibitor, an even more dramatic antitumor effect was observed. This study was published in Cancer Cell. Finally, a collaborative study with the Gabrilovich Lab and researchers at University of Pittsburgh, published in Nature Communications, shed light on the defective function of tumor-associated dendritic cells (DCs), specialized immune cells that expose antigens on their surface to activate a T cell-mediated immune response. This research explains why DCs are not effective at inducing antitumor immune responses. DCs are essential players when it comes to antitumor immunity because they allow T cells that have the ability to kill cancer cells to recognize their targets. This is also an essential function for the success of cancer vaccines and immunotherapy. Results showed that tumor-associated DCs accumulate chemically altered lipids that are the result of oxidative modification, which in turn had the ability to modify their function. Gabrilovich and his colleagues discovered some of the target proteins that interact with these modified lipids, which could serve as important therapeutic targets in the future.

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SPOTLIGHT ON...

National Institutes of Health selects Kavitha Sarma, Ph.D., for Innovator Award

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avitha Sarma, Ph.D., assistant professor in Wistar’s Gene Expression and Regulation Program, was awarded the National Institutes of Health (NIH) Director’s New Innovator Award (DP2) for her research on “Epigenetic regulation through the formation and resolution of R-loops.” As part of the NIH High-Risk, High-Reward Research program, this award supports a small number of early career investigators of exceptional creativity who propose innovative research approaches that have the potential to produce a major impact on broad, important problems in biomedical and behavioral research. Sarma’s research interest revolves around the dynamic modifications of the architecture of chromatin, the complex of DNA, RNA, and proteins within the nucleus of our cells. She joined Wistar in 2016 and established her lab to study how chromatin and epigenetic modifications impact gene expression during normal cellular function and disease. R-loops are three-stranded nucleic acid structures that form naturally during transcription and play roles in fine-tuning gene expression. However, at the same time, R-loops can pose a threat to genome integrity because one of the DNA molecules in the structure is exposed to damage. In fact, the presence of R-loops has been associated with neurodegenerative disease and cancer, although the exact mechanisms are unclear. In the past decade, the study of R-loops has become a vibrant research field. Researchers are trying to explain how cells keep at bay the negative effects of R-loops while allowing their positive functions. “Through new tools we have developed, we are beginning to learn where R-loops form across the genome, but this information is not sufficient to understand their role in physiology and disease,” said Sarma. “To obtain a complete picture of the process, we need to extend our knowledge of the protein factors that regulate formation and resolution of R-loops.” Sarma and her team set to develop new biochemical and proteomic methods for the identification of these factors, which will provide insights into how R-loops are regulated and, ultimately, how they affect gene expression. R-loops represent a common molecular feature of a group of neurodegenerative genetic conditions called repeat expansion

KAVITHA SARMA, Ph.D. Assistant Professor, Gene Expression & Regulation Program

disorders, such as amyotrophic lateral sclerosis (ALS) and fragile X syndrome. These conditions are characterized by abnormal expansion of repeated DNA sequences. Some regions of our genome are composed by repetitive sequences of DNA that are prone to abnormal expansion during transmission of the genetic material from parent to child and during the lifetime of a person. When this happens, the protein product of the affected gene is altered or its expression is suppressed, causing disease. Identifying R-loop regulators may help pinpoint potential novel therapeutic avenues for repeat expansion neurodegenerative disorders. The results from Sarma’s research may be extended to disorders and cancers that are associated with mutations in R-loop regulators. “Learning how R-loops are regulated will allow us to unravel these structures when they have caused disease.” “The New Innovator Award is ideal for Kavitha,” said Dario C. Altieri, M.D., president and CEO of The Wistar Institute, director of the Wistar Cancer Center and the Robert and Penny Fox Distinguished Professor. “She is a highly creative scientist, and the support from this award will open unique opportunities to further our understanding of chromatin structures in neurodegeneration and cancer.”

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RESEARCH HIGHLIGHTS

Discovering the Future of Medicine The research underway in our labs today will lead to breakthroughs tomorrow. Our scientists have revealed new information on therapy response in older melanoma patients, how our genome is organized and the ends of our chromosomes are protected, and how normal cells, cancer cells and immune cells respond to stressful environmental conditions. The studies detailed below, along with other groundbreaking discoveries at Wistar, provide fundamental knowledge that advances our understanding of biomedical research.

Sections of human skin showing loss of the Klotho protein with aging.

Anti-diabetic Drug Might Benefit Melanoma Older Patients An anti-aging protein and an anti-diabetic drug could work in tandem to help combat melanoma in older patients. The lab of Ashani Weeraratna, Ph.D., Ira Brind Professor and co-leader of the Immunology, Microenvironment and Metastasis Program, demonstrated that the anti-diabetic drug rosiglitazone could be used to promote the expression of the Klotho protein. Prior studies have shown that increased levels of Klotho reduce the levels of another protein called Wnt5A, which promotes metastatic progression, resistance to therapy and poorer prognosis in melanoma patients.

However, while this anti-diabetic drug inhibited tumor growth in models for older patients, it actually accelerated tumor growth in younger models. “Our new study indicates that a differential therapeutic approach can be beneficial for older patients in melanoma and suggests that age should be taken into account to design better treatments for certain cohorts of patients,� Weeraratna said. The study was published in the journal Clinical Cancer Research.

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Atomic Structure of a Protein Complex That Protects Telomeres Emmanuel Skordalakes, Ph.D., associate professor in the Gene Expression and Regulation Program, and colleagues unveiled part of the protein complex that protects telomeres—the ends of our chromosomes. These findings, published in Nature Communications, help explain how a group of genetic mutations associated with this protein complex contribute to various cancers. Telomeres are the protective structures at the end of chromosomes Chromosomes visualized by FISH (fluorescence in-situ hybridization). Red spots indicate telomeres. and are essential for the faithful replication and protection of our genome. A key component of the telomere protecting mechanism is a multi-protein complex called shelterin. Shelterin protects chromosome ends from being recognized as DNA damage sites and triggering DNA damage response mechanisms. The atomic structure of the protein-protein interaction between the two components of the shelterin complex, POT1 and TPP1 was described in the study. Several gene mutations affect portions of POT1 in familial melanoma, glioma and chronic lymphocytic leukemia. “Based on our data, we suggest that the cancer-associated mutations reported in POT1 affect the integrity of telomeres, leading to chromosomal abnormalities and in turn genomic instability, which is a hallmark of cancer progression,” Skordalakes said. “We think that this mechanism works in combination with other fundamental genetic defects characteristic of these malignancies.”

New Function Discovered for ADAR1 In a study that appeared in Nature Structural & Molecular Biology, Kazuko Nishikura, Ph.D., professor in the Gene Expression and Regulation Program, and her team identified a new function for ADAR1, an RNA editing protein that her lab has been researching for many years. There are two forms of the ADAR1 protein: ADAR1p110 and ADAR1p150. While several biological functions had been revealed for ADAR1p150, little was known about the role of ADAR1p110 in vivo. This study showed that ADAR1p110 regulates the response of cells to certain stressors, including UV radiation, by protecting them from

dying as a result of a process called apoptosis, a form of programmed cell death. When cells were exposed to stressors such as UV radiation, ADAR1p110 transiently moved from its normal location in the nucleus and nucleoli of a cell into the cytoplasm, where it protects a defined set of mRNAs from degradation. Many of these mRNAs decode genes involved in preventing apoptotic cell death, leading researchers to conclude that ADAR1p110 protects cells from stress-induced apoptosis by protecting anti-apoptotic mRNAs from degradation. “Now that we have a well-defined function for ADAR1p110, we can work to understand its role in postnatal development and disease, in particular cancer,” said Nishikura.

Model of the region of the ADAR1 protein that interacts with RNA.

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RESEARCH HIGHLIGHTS

How T Lymphocytes Cope With Metabolic Stress The presence of tumor infiltrating T lymphocytes (TILs) in solid tumors is often associated with better clinical outcomes and better patient responses to some immunotherapeutic treatments. However, TILs undergo progressive loss of functions due to metabolic stress as they compete with tumor cells for oxygen and nutrients in the tumor microenvironment. A study published in the journal Cancer Cell and led by Hildegund C.J. Ertl, M.D., professor and member of Wistar’s Vaccine & Immunotherapy Center, revealed that T lymphocytes cope with metabolic stress through a process that can be pharmacologically promoted to enhance their antitumor activity. “The mechanisms behind TILs exhaustion are poorly understood,” said Ertl. “Considering their central importance for cancer immunotherapy, we believe that our findings may have critical implications to boost the efficacy of T cell-based therapies for different cancer types.” Ertl and colleagues showed that low oxygen levels combined with low glucose availability cause TILs to change their source for energy production from glucose to fatty acids, the building blocks of fat. They also proved that fibrates, a class of FDA-approved drugs used to lower cholesterol levels, can further induce this metabolic shift and instructs the T cells to increase their use of fatty acids for energy production, thus improving TILs effector functions and their ability to delay tumor progression in two mouse models of melanoma. Importantly, these drugs can also synergize with immune checkpoint blockade therapy, improving the efficacy of this melanoma immunotherapy.

Electron microscopy image of a TIL cell showing mitochondrial stress.

Immunofluorescence image of a cell showing localization of mitochondria (blue). Cell skeleton is pink and nucleus is yellow.

Metastasis Suppressor Pathway Coordinated by Mitochondrial Protein A study led by Dario C. Altieri, M.D., president and CEO of The Wistar Institute, director of The Wistar Institute Cancer Center, and the Robert & Penny Fox Distinguished Professor, identified a mitochondrial variant of the protein syntaphilin, or SNPH, and described a novel metastasis suppressor pathway. The research was published in the Journal of Clinical Investigation. Tumor cells must be able to adapt to unfavorable environmental conditions, including low oxygen, scarcity of nutrients and high levels of toxins. This process, referred to as tumor plasticity, requires them to reprogram their metabolism to serve their energy needs. Under stressful conditions, tumor cells are often forced to operate a switch between proliferation and motility, both of which pose high energy requirements, shifting the balance between local tumor growth and metastatic dissemination. In this study, Altieri and colleagues described a novel metastasis suppressor pathway orchestrated by SNPH, a protein that was originally only found in neurons. They discovered a novel, shorter variant of the protein, which is present in many normal and tumor tissues and localizes in mitochondria, the cellular structures where energy is generated. This SNPH variant acts as a “rheostat,” or a molecular switch, between tumor cell proliferation and metastasis. In vivo studies in mouse models of melanoma confirmed the role of SNPH in controlling metastasis and showed that mitochondrial localization is required for SNPH functions. “Metastatic disease is the primary cause of death for cancer patients,” said Altieri. “Our findings contribute much-needed information on tumor plasticity driving metastatic dissemination and may lead to new therapeutic approaches.”

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Genome Architecture Caught in Motion The lab of Ken-ichi Noma, Ph.D., associate professor in the Gene Expression and Regulation Program, uncovered new aspects of the three-dimensional organization of the genome, specifically how the genetic material is compacted and de-compacted in a timely fashion during the different phases of the cell cycle. The research was published in Nature Structural & Molecular Biology. The genetic information contained inside each of our cells is encoded by several feet worth of DNA molecules. Such an enormous amount of genetic material is packed into a microscopic space by folding it into a highly organized complex of DNA and proteins called chromatin. Although already significantly compacted, chromatin needs to be further condensed upon entry into Visualization of a contact map, used to analyze the contacts mitosis, the process that divides each cell into two identical cells, in order to between distant regions of the genome. faithfully segregate the genetic material. Noma and colleagues have previously described how two protein complexes called condensin and cohesin mediate the formation of functional genome-organizing structures called topological domains by establishing contacts that bring distantly located DNA regions closer together. In the new study, the lab applied similar genomic methodology to dissect the condensation and de-condensation of chromatin over time, following the formation and decay of chromatin contacts throughout the different phases of the cell cycle. Alterations of the three-dimensional structures of the genome are linked to genetic diseases and cancer, presenting a powerful example of how basic cellular processes are relevant for disease. “The field is still in an early discovery phase but our study adds new insight into a fundamental biological process that may assist the development of novel therapeutic strategies in the future,” Noma said.

Combination of Two Inhibitors Is Effective Against Ovarian Cancer Combining PARP inhibitors, recently approved for the treatment of BRCA-mutant ovarian cancer, with another small molecule inhibitor was effective to treat ovarian cancers Immunofluorescence images showing the consecutive phases of cell division. without BRCA1 and BRCA2 gene mutations. This discovery was made in the lab of Rugang Zhang, Ph.D., deputy director of The Wistar Institute Cancer Center, professor and co-leader of the Gene Expression and Regulation Program. “By blocking another member of the DNA repair pathway, PARP inhibitors are an effective strategy to kill BRCAmutant cancer cells and have recently been approved for the treatment of ovarian cancer, but how to expand their use into BRCA-proficient cancers remained to be explored,” Zhang said. “We identified an effective strategy to sensitize BRCA-proficient ovarian cancers to PARP inhibitors and extend their clinical efficacy to a larger group of patients.” The team tested the combination of PARP and BET inhibitors in vivo in a mouse model of ovarian cancer with normal BRCA1 and BRCA2. While neither of the two inhibitors alone had an effect on tumor growth, the combination of the two resulted in significant reduction of tumor burden without any overt toxicity. Study results were published in Cell Reports.

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SCIENTIFIC SYMPOSIA

Bringing Top Scientific Minds to the Region Early engagement and open communication with scientific partners and industry is the key to advancing scientific innovations, while accelerating drug development to bring impactful new medicines and diagnostics to people in need. Wistar’s scientific symposia bring together scientists from academia, bio-pharma industry and government to present and discuss their latest research, while allowing for effective exchange and networking among attendees. In 2017, Wistar hosted three major scientific conferences that brought together speakers and guests from around the world.

Epigenetics in Cancer Scientific Symposium AP RIL 2 5, 2 017

Cancer genomics has revealed that epigenetic pathways are frequently mutated in different tumor types and epigenetic therapy is emerging as one of the most promising tools to treat cancer. During this symposium, Wistar welcomed a full house of leaders in epigenetics research to discuss the most recent advances in the field and their potential translational applications. This symposium was sponsored Wistar’s Gene Expression and Regulation Program.

The Noreen O’Neill Melanoma Research Symposium: Advances in Therapy & Biology JUN E 2 0, 2 0 1 7

Wistar’s melanoma research community reached one of its most important moments at the first Noreen O’Neill Melanoma Research Symposium—a meeting that drew nearly 200 attendees and brought an international panel of experts to Philadelphia to discuss the most advanced topics in melanoma research. The symposium coincided with the establishment of the Noreen O’Neill Melanoma Research Fund at The Wistar Institute, through which Wistar will continue to advance transformative melanoma research and advocate for melanoma awareness and education.

Images from the Melanoma (left) and the Epigenetics in Cancer (right) symposia.

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Neurovirology & Neuroimmunology Symposium SE P T E MB E R 2 8 , 2 0 1 7

The 3rd Annual Philadelphia-wide Symposium on Neurovirology & Neuroimmunology, held for the first time at Wistar, brought together a record-setting number of more than 200 experts and trainees from throughout the region. This symposium was led by the Neurovirology Training Group, a collaborative partnership between representatives from The Wistar Institute, Children’s Hospital of Philadelphia, University of Pennsylvania, Thomas Jefferson University and Fox Chase Cancer Center.


PA R T N E R S I N D I S C O V E R Y

Wistar Launches Life Sciences Consortium to Simplify and Accelerate Research Collaboration Fostering long-term collaborations and helping new and prospective partners speed access to preclinical discovery research is an essential element of the drug discovery process. In 2017, Wistar along with 12 regional academic institutions launched the Philadelphia Research Consortium to move research discoveries into the R&D pipeline and accelerate products into future drugs and therapeutics through a streamlined sponsored research agreement. “The goal is to foster preclinical collaboration between start-ups and our research labs and advance and de-risk our own programs,” said Heather Steinman, Ph.D., MBA, Wistar vice president of Business Development and executive director of Technology Transfer, who spearheaded the development of the Consortium. “We have all the talent, research and resources in the Philadelphia region, and we’re all working together to create a vibrant life sciences ecosystem.” The Consortium allows for startup and biotech partners to leverage the collective research strengths of Philadelphia’s vibrant life sciences community. With fledgling startups and biotechs in mind, Steinman’s concept establishes that Consortium members pledge to use a sponsored research agreement that serves as a universal, standard template that encourages productive partnerships and swift collaboration. The vision is two-fold: enable transformative, potentially lifesaving scientific progress, and catalyze productive, long-term collaborations between the Philadelphia academic research community and for-profit research and development partners, specifically targeting life sciences start-ups. Partners can focus on the key experiments required to advance therapeutic programs through the proof-of-concept stage without negotiating multiple and often cumbersome contracts. These relationships could increase the likelihood of innovative early stage discoveries successfully moving from the laboratory to the marketplace.

THE CONSORTIUM CONSISTS OF:

• Baruch S. Blumberg Institute • Children’s Hospital of Philadelphia • Children’s National Health System • Drexel University • Lankenau Institute for Medical Research (part of Main Line Health) • Lehigh University • Monell Chemical Senses Center • Penn State • Penn State College of Medicine • Temple University • The Wistar Institute • Thomas Jefferson University • University of the Sciences

“The goal is to foster preclinical collaboration between start-ups and our research labs and advance and de-risk our own programs.” —Heather Steinman, Ph.D., MBA

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F O U N D AT I O N E N G A G E M E N T

Wistar Receives $1.4M from the Bill & Melinda Gates Foundation to Develop a Synthetic DNA Vaccine Against Malaria Malaria is a leading cause of death in infants and children in developing countries across the globe, a disease burden that accounted for 216 million cases worldwide and 445,000 deaths in 2016.

Public and private foundations as well as government and academic sectors continue to pursue new vaccine candidates to stop the spread of malaria. To that end, Wistar has received its second Gates Foundation grant for a promising DNA vaccine platform developed in the lab of David Weiner, Ph.D., Wistar executive vice president and director of the Vaccine & Immunotherapy Center. Weiner, along with collaborators from Inovio Pharmaceuticals, Inc., and Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health, are furthering a synthetic DNA vaccine that drives robust antibody and T cell immune responses. The Gates Foundation support confirms the imminent need to pursue other vaccine candidates that will offer strong, potent and durable protection. “DNA vaccines have an important public health potential to rapidly impact emerging pandemics, as this technology has conceptual advantages: safety, development, speed of production, field stability, and deliverability for vaccine and immunotherapy development,” said Weiner. “These synthetic DNA approaches can be developed for important infectious diseases, and with our collaborators, we have shown this consistently by rapidly engineering multiple synthetic DNA vaccines and advancing them to clinical study with positive outcomes of safety and immune potency.” These next generation vaccines could become the tools we need to end malaria as we know it.

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E D U C AT I O N

Evolution of the Biomedical Technician Training Program Wistar Launches the Biomedical Research Technician Apprenticeship, the First Non-Traditional Apprenticeship in Biomedical Research

On May 11, 2017, Wistar’s Biomedical Research Training (BRT) Apprenticeship was approved as an official, credentialed, nontraditional apprenticeship of the Commonwealth of Pennsylvania. This apprenticeship is the first of its kind in the nation and was developed to train a skilled and stable workforce of entry level biomedical research assistants. The BRT Apprenticeship expands upon the structure and concepts of Wistar’s Biomedical Technician Training (BTT) Program, which was created in 2000 by William Wunner, Ph.D., Wistar director of Academic Affairs and director of Outreach Education and Technology Training Programs, in partnership with the Community College of Philadelphia to reinforce the region’s workforce with experienced lab technicians. This evolution showcases Wistar’s critical role in science education and training in the Philadelphia region, affirming the value of being globally connected and locally relevant. The BRT Apprenticeship Program offers apprentices a career pathway to become biomedical research technicians in both academic and corporate research laboratory environments. Apprentices are trained by experts in their field, who share their knowledge of real-world work environments, with additional technical classroom instruction that ensures the apprentice masters all aspects of the job.

“This program provides students of diverse backgrounds with hands-on biomedical research experience in laboratories while meeting the needs of the biomedical sector with a select employee talent pool,” said Wunner. Through advanced training and on-the-job opportunities, trainees acquire skillsets to facilitate experimental procedures, manage a laboratory and monitor lab safety, conduct data analysis of research experiments, and utilize various other highly skilled techniques with the goal of supporting a lead scientist in the laboratory. Most importantly, they “earn while they learn” the skills needed for the job. This fully recognized training model will help serve the workforce needs of the region’s burgeoning life sciences community with experienced lab technicians. “As Congress now authorizes a budget in support of funding innovative, job-driven approaches that expand new apprenticeships in high growth new industries, we are proud that the BRT Program is the first science, technology, engineering, mathematics (STEM), non-traditional apprenticeship model supporting the development of the biotech labor force in Pennsylvania,” said Dario C. Altieri, M.D., president and CEO of The Wistar Institute. “Today more than ever, it is critical to obtain specialized skills in our knowledge-based economy, and this program moves the innovation lifecycle forward to support a vibrant, growing life sciences community in our state.”

L to R: Dario Altieri, M.D., president & CEO, The Wistar Institute; Kathy Manderino, Secretary of the Pa. Department of Labor & Industry; William Wunner, Ph.D., director of Outreach Education and Technology Training, The Wistar Institute; Eileen Cipriani, Deputy Secretary for Workforce Development; Eric Ramsay, director of Apprenticeship & Training Office; and Donald Guy Generals, Ed.D., president of the Community College of Philadelphia.

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FA C U LT Y D E V E L O P M E N T S

Wistar’s Newest Researchers In 2017, Wistar appointed several new and established scientists to carry out innovative research in Wistar’s Robert & Penny Fox Tower, which occupies almost 90,000 square feet of open-concept lab space.

CHI VAN DANG, M.D., Ph.D Scientist, medical oncologist and National Academy of Medicine member Chi Van Dang, M.D., Ph.D., was appointed strategic advisor to the President & CEO and professor in the Molecular & Cellular Oncogenesis Program at Wistar. Dang is also the scientific director of the Ludwig Institute for Cancer Research in New York, shapes scientific strategy for Ludwig and oversees operations of its Lausanne, Oxford and San Diego Branches. Wistar hosts Dang’s Ludwig Laboratory, which focuses on cancer and immune cell metabolism and the MYC cancer gene. This gene was shown by Dang and his lab to control gene expression that affects metabolism and cancer cell growth.

JOSEPH SALVINO, Ph.D Wistar hired its first medicinal chemist. Joseph Salvino, Ph.D., was appointed professor in the Molecular & Cellular Oncogenesis Program and scientific director of Wistar’s Molecular Screening & Protein Expression Facility. His research is directed at drug discovery and development, namely in identifying novel small molecule lead compounds, and provides a strong basis for collaboration with all Wistar researchers and the research community in the region. Through the design and creation of novel chemical analogs, Salvino can optimize early stage compounds and identify potential preclinical drug candidates or future therapeutic agents against a new biological target.

New Leadership in Education Brian Keith, Ph.D., was appointed Wistar’s first Dean of Biomedical Studies to further Wistar’s educational mission of training scientists and priming workforce development programs and opportunities. Keith joins the Institute at a time of abundant growth across its STEM educational programs. Both a scientist and a teacher, he brings knowledge of and success in the field of biomedical research to shape a broad-based, impactful, and forward-looking vision for the educational mission of the Institute.

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Three scientists joined the faculty of Wistar’s Vaccine & Immunotherapy Center:

Farokh Dotiwala, M.B.B.S., Ph.D., was appointed assistant professor. His research focuses on the mechanisms of killer immune cells—such as natural killer and CD8 T cells—and how they target and destroy pathogens in host cells. His work entails studying and developing therapeutic strategies against infections that were once thought to be drug-resistant. Dotiwala studies how granzymes—the weapons of immune killer cells—attack and disable the infective pathogen and not the host cell.

Mohamed Abdel-Mohsen, Ph.D., was appointed assistant professor. His innovative research approach to HIV centers on the exciting field of glycoimmunology and the role of sugar molecules in mediating cellular processes that are central to immune regulation and human diseases. Abdel-Mohsen’s research focuses on diverse aspects of HIV pathogenesis, including intrinsic immunity, host-virus interactions, HIV latency, and HIV genetic variability.

Daniel Kulp, Ph.D., was appointed associate professor. Kulp’s research centers on how to best engineer protective immune responses against emerging and harmful infectious diseases using computer designed vaccines and engineered antibody therapies. His focus is on HIV and arenaviruses, a family of viruses that include Lassa virus (LASV), a disease that causes hemorrhagic fever and affects hundreds of thousands of people in Africa each year. Kulp’s unique computational and engineering expertise also allows him to translate his work for the development of innovative cancer therapeutics.

Deputy Director Appointment Rugang Zhang, Ph.D., professor and co-leader of the Gene Expression & Regulation Program, was appointed deputy director of Wistar’s Cancer Center. Zhang joined Wistar as an associate professor in 2012 and was promoted to the rank of full professor in 2015. He is also an adjunct faculty at University of Pennsylvania.

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SHARED RESOURCES The Wistar Institute Shared Resources, also known as core facilities, provide technological and professional expertise to address our investigators’ research requirements, acting as an efficient “force multiplier”. Many of Wistar’s Shared Resources are approved by the National Cancer Institute (NCI) and supported by our Cancer Center Support Grant. The Animal Facility Shared Resource facilitates research through compassionate and efficient management of animal populations. The Bioinformatics Shared Resource continuously develops new and efficient approaches to data analysis as a response to emerging research needs. The Biomedical Research Support Core provides a robust infrastructure to support patient-oriented research. The BRSC manages the resources needed to conduct clinical studies. The Biosafety Level-3 (BSL-3) Facility provides a safe environment for working with infectious agents and offers training for Wistar’s research and laboratory personnel. The Flow Cytometry Shared Resource provides users with the technological resources and professional assistance for high-quality, multi-parameter flow cytometry analyses and sorting. The Cell Culture Facility at Fox Chase Cancer Center serves as a primary resource for monoclonal antibody (mAb) production by Wistar researchers. The Transgenic Mouse Facility at Fox Chase Cancer Center provides researchers with access to technology and expertise for generating transgenic and genetically modified mouse lines.

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The Wistar Institute and the Gene Editing Institute at Christiana Care’s Helen F. Graham Cancer Center & Research Institute have a partnership that aims to accelerate breakthrough cancer research in the human genome. The Gene Editing Institute is integrated into Wistar’s Molecular Screening Shared Resource. The Genomics Shared Resource supports several state-of-the-art platforms for a wide variety of nucleic acid-based studies and serves as a hub for consultation and scientific interaction relating to these methods. The Histotechnology Shared Resource provides services for fixing, processing and paraffin or OCT-embedding of all types of tissues for light microscopy. The Imaging Shared Resource provides access to optical imaging systems and assistance with advanced image analysis solutions. The imaging of complex cellular structures is used to determine how regulatory events within cells, tissues and organisms impact normal and pathological processes. The Molecular Screening & Protein Expression Shared Resource enables researchers to discover small molecule compounds and molecular genetic targets suitable to further study the protein functions, signaling pathways, and cells in pure or complex biological systems. The Proteomics and Metabolomics Shared Resource provides high-sensitivity proteomics and metabolomics analyses using state-ofthe-art mass spectrometry instruments and methods. The Research Supply Center furnishes a large selection of plasticware for all scientists at the Institute.

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A D M I N I S T R AT I O N & F A C U LT Y LEADERSHIP & ADMINISTRATION Listed in alphabetical order

Dario C. Altieri, M.D. President & CEO

THE WISTAR INSTITUTE CANCER CENTER

Jessica Blodgett, MBA Director, Research & Administrative Services

ADMINISTRATION

SHARED RESOURCES

Dario C. Altieri, M.D. Director

SCIENTIFIC DIRECTORS

Van Cherington, Ph.D. Director, Science Administration Chief Compliance Officer*

Rugang Zhang, Ph.D. Deputy Director

Chi Van Dang, M.D., Ph.D. Strategic Advisor to the President Jennifer Evans Stacey, Esq. Vice President, General Counsel, Secretary & Government Relations Jeffrey Fahnoe Chief Information Officer Brian Keith, Ph.D. Dean, Biomedical Studies Jo-Ann Mendel, MBA, PHR Vice President, Human Resources Luis J. Montaner, D.V.M., D.Phil. Vice President, Scientific Operations Maureen Murphy, Ph.D. Associate Vice President, Faculty Affairs Anita Pepper, Ph.D. Vice President, Institutional Advancement

Brian Keith* Associate Director, Education

Tara Yates Director, Communications & Marketing

Luis J. Montaner, D.V.M., D.Phil. Joseph Salvino, Ph.D. Louise C. Showe, Ph.D.

Maureen Murphy, Ph.D.** Associate Director, Education & Career Development

MANAGING DIRECTORS

David W. Speicher, Ph.D.

Livio Azzoni, M.D., Ph.D.

Marianne M. O’Neill Associate Director, Cancer Center Support Grant Finances

Joel Cassel, B.S.

Nicholas J. Petrelli, M.D. Associate Director, Translational Research

Jeffrey S. Faust, B.S., MBA

Lisa J. Sideras Associate Director, Cancer Center Administration

Andrew V. Kossenkov, Ph.D.

Mark S. Drinker Assistant Director, Shared Resources Operations

Joseph Trainor, CPA Chief Financial Officer

William H. Wunner, Ph.D. Director, Outreach & Technology Training Director, Academic Affairs

Qing Chen, M.D., Ph.D.

Luis J. Montaner, D.V.M., D.Phil. Associate Director, Shared Resources

Heather Steinman, Ph.D., MBA Vice President, Business Development Executive Director, Technology Transfer

David B. Weiner, Ph.D. Executive Vice President

Andrew J. Caton, Ph.D.

NOTES

* As of July 2017 ** Until June 2017 *** As of October 2017 † Left the Institute in March of 2017 ‡ Left the Institute in May of 2017 § Left the Institute in December of 2017

James E. Zalesky Director, Facilities *As of March 2017 24 // THE WISTAR INSTITUTE

Denise DiFrancesco, AS, RLATG, CMAR, ILAM

James E. Hayden, B.A., RBP, FBCA

R. Sonali Majumdar, M.S. Hsin-Yao Tang, Ph.D.


These lists are as of December 31, 2017

Gene Expression & Regulation Program

Molecular & Cellular Oncogenesis Program

SCIENTIFIC LEADERSHIP

SCIENTIFIC LEADERSHIP

Paul M. Lieberman, Ph.D. Program Leader

Maureen Murphy, Ph.D. Program Leader

Rugang Zhang, Ph.D. Program Co-Leader

David W. Speicher, Ph.D. Program Co-Leader

FACULTY

FACULTY

P R OF E S S OR S

PROFESSORS

Paul Lieberman, Ph.D. Hilary Koprowski Professor

Maureen Murphy, Ph.D.

Rugang Zhang, Ph.D. Kazuko Nishikura, Ph.D. Frank Rauscher, III, Ph.D.

David W. Speicher, Ph.D. Chi Van Dang, M.D., Ph.D. Meenhard Herlyn, D.V.M., D.Sc. Qin Liu, M.D., Ph.D.

AS S O C I AT E P R OFE S S O R S

Joseph Salvino, Ph.D.

Ken-ichi Noma, Ph.D.

Louise C. Showe, Ph.D.

Emmanuel Skordalakes, Ph.D.

ASSISTANT P ROFESSORS

AS S I STA N T P R O F E S S O R S

Alessandro Gardini, Ph.D. Kavitha Sarma, Ph.D. R E S E A R C H AS S ISTAN T P R OF E S S OR

Masayuki Sakurai, Ph.D.***

Zachary Schug, Ph.D. Jessie Villanueva, Ph.D. R ESEARCH ASSISTANT PROFESSORS

Immunology, Microenvironment & Metastasis Program SCIENTIFIC LEADERSHIP Dmitry I. Gabrilovich, M.D., Ph.D. Program Leader Ashani Weeraratna, Ph.D. Program Co-Leader

FACULTY P ROFESSORS

Dmitry I. Gabrilovich, M.D., Ph.D. Christopher M. Davis Professor Dario C. Altieri, M.D. Robert & Penny Fox Distinguished Professor Andrew Caton, Ph.D. Brian Keith, Ph.D. Luis J. Montaner, D.V.M., D.Phil. Herbert Kean, M.D., Family Endowed Chair Professor David B. Weiner, Ph.D. W.W. Smith Charitable Trust Professor in Cancer Research ASSOCIATE P ROFESSO R S

Mizuho Kalabis, M.D., Ph.D.†

Chih-Chi Hu, Ph.D.

Clemens Krepler, Ph.D.‡

Qihong Huang, M.D., Ph.D.§

Rajasekharan Somasundaram, Ph.D.

Ashani Weeraratna, Ph.D. Ira Brind Associate Professor ASSISTANT P ROFESSOR S

Qing Chen, M.D., Ph.D. Yulia Nefedova, M.D., Ph.D. Erica L. Stone, Ph.D.

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A D M I N I S T R AT I O N & F A C U LT Y

THE WISTAR INSTITUTE VACCINE & IMMUNOTHERAPY CENTER

Melanoma Research Center Meenhard Herlyn, D.V.M., D.Sc. Director MEMBERS

Jessie Villanueva, Ph.D.

David B. Weiner, Ph.D. Director

Ashani Weeraratna, Ph.D.

FACULTY P R OF E S S OR S

David B. Weiner, Ph.D. W.W. Smith Charitable Trust Professor in Cancer Research Andrew J. Caton, Ph.D.1

Center For Systems & Computational Biology David W. Speicher, Ph.D. Director Louise C. Showe, Ph.D. Associate Director

Jan Erikson, Ph.D.2 Hildegund C.J. Ertl, M.D.

MEMBERS

Luis J. Montaner, D.V.M., D.Phil. Herbert Kean, M.D., Family Endowed Chair Professor

Ken-ichi Noma, Ph.D.

ASS OC I AT E P R OF E SS O R

Zachary Schug, Ph.D.

Daniel Kulp, Ph.D.

Emmanuel Skordalakes, Ph.D.

1

Qin Liu, M.D. Ph.D.

ASS I STA NT P R OF E SS O R S

Mohamed Abdel-Mohsen, Ph.D. Farokh Dotiwala, M.B.B.S., Ph.D.

PROFESSORS EMERITI

Kar Muthumani, Ph.D.

Clayton Buck, Ph.D. 1 2

Secondary appointment Retired in December 2017

Roger M. Burnett, Ph.D. Walter Gerhard, M.D. Dorothee Herlyn, D.V.M., D.Sc. Elliot Levine, Ph.D. Stanley Plotkin, M.D. Leonard Warren, M.D., Ph.D. Zofia Wroblewska, M.D. PRESIDENT EMERITUS

Russel E. Kaufman, M.D.

LEFT Flu virus.


A DJ U N C T P R OF E S S OR S

Pablo Tebas, M.D. University of Pennsylvania

Stephen M. Albelda, M.D. University of Pennsylvania

Jeffrey D. Winkler, Ph.D. University of Pennsylvania

Timothy M. Block, Ph.D. Drexel University

Xiaowei Xu, M.D., Ph.D. University of Pennsylvania

Jose Conejo-Garcia, M.D., Ph.D. Moffit Cancer Center

ADJ U NCT ASSOCIATE P ROFESSORS

ADJUNCT FACULTY

Dennis E. Discher, Ph.D. University of Pennsylvania Cesare Furlanello, Ph.D. Centre for Scientific and Technological Research, Trento, Italy Mark I. Greene, M.D., Ph.D. University of Pennsylvania Wei Guo, Ph.D. University of Pennsylvania Thanos D. Halazonetis, D.D.S., Ph.D. University of Geneva, Geneva, Switzerland Katherine A. High, M.D. Children’s Hospital of Philadelphia/Spark Therapeutics Jay R. Kostman, M.D. University of Pennsylvania/Philadelphia FIGHT Ronen Marmorstein, Ph.D. University of Pennsylvania Steven B. McMahon, Ph.D. Thomas Jefferson University Pat Morin, Ph.D. University of Pennsylvania Richard G. Pestell, M.D., Ph.D. Lankenau Institute for Medical Research Nicholas J. Petrelli, M.D. Helen F. Graham Cancer Center & Research Institute George C. Prendergast, Ph.D. Lankenau Institute for Medical Research Alexander Roesch, M.D. The Saarland University Hospital, Homburg, Germany Anil K. Rustgi, M.D. University of Pennsylvania

Ravi K. Amaravadi, M.D. University of Pennsylvania Ronny Drapkin, M.D., Ph.D. University of Pennsylvania

Michael J. Guarino, M.D. Helen F. Graham Cancer Center & Research Institute Scott Hall, M.D. Helen F. Graham Cancer Center & Research Institute Neil G. Hockstein, M.D. Helen F. Graham Cancer Center & Research Institute Stephanie Jean, M.D. Helen F. Graham Cancer Center & Research Institute

F. Bradley Johnson, M.D., Ph.D. University of Pennsylvania

Jamil Khatri, M.D. Helen F. Graham Cancer Center & Research Institute

Karam C. Mounzer, M.D. University of Pennsylvania/Philadelphia FIGHT

Eric B. Kmiec, Ph.D. Helen F. Graham Cancer Center & Research Institute

Donald M. O’Rourke, M.D. University of Pennsylvania

Christopher Koprowski, M.D. Helen F. Graham Cancer Center & Research Institute

Julia C. Tchou, M.D., Ph.D. University of Pennsylvania Zhi Wei, Ph.D. New Jersey Institute of Technology ADJ U NCT ASSISTANT P ROFESSORS

Devraj Basu, M.D., Ph.D. University of Pennsylvania Rumela Chakrabarti, Ph.D. University of Pennsylvania David S. Garlick, Ph.D. Histo-Scientific Research Laboratories

Gregory A. Masters, M.D. Helen F. Graham Cancer Center & Research Institute Christopher R. Mitchell, M.D. Helen F. Graham Cancer Center & Research Institute Eric Montgomery, M.D. Helen F. Graham Cancer Center & Research Institute Charles R. Mulligan, M.D. Helen F. Graham Cancer Center & Research Institute

Fiona Simpkins, M.D. University of Pennsylvania

Brian T. Nam, M.D. Helen F. Graham Cancer Center & Research Institute

ADJ U NCT/AFFILIATE AP P OINTMENTS

Pulak Ray, M.D. Helen F. Graham Cancer Center & Research Institute

Joseph J. Bennett, M.D. Helen F. Graham Cancer Center & Research Institute Mark E. Borowsky, M.D. Helen F. Graham Cancer Center & Research Institute Mark G. Cadungog, M.D. Helen F. Graham Cancer Center & Research Institute

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Gary B. Witkin, M.D. Helen F. Graham Cancer Center & Research Institute Robert L. Witt, M.D. Helen F. Graham Cancer Center & Research Institute


BOARD OF TRUSTEES

OFFICERS C HA IR

Helen P. Pudlin, Esq. Retired Executive Vice President and General Counsel The PNC Financial Services Group, Inc. V ICE C H A I R

Daniel K. Fitzpatrick, C.F.A.

Arthur M. Pappas

President

Managing Partner

Citizens Bank Park PA/NJ/DE

Pappas Ventures

Head of National MidCorporate and Industry Verticals

Wendell Pritchett, J.D., Ph.D.***

Robert A. Fox

University of Pennsylvania

Chairman and CEO

Richard M. Horowitz

R.A.F. Industries, Inc.

President

John A. Fry*

RAF Industries, Inc. SEC R ETA RY

Jennifer Evans Stacey, Esq. Vice President, General Counsel, Secretary and Government Relations The Wistar Institute TREASU R E R

Joseph Trainor Chief Financial Officer The Wistar Institute

President Drexel University L. Patrick Gage, Ph.D. Founder enGage Biotech Consulting George W. Gephart, Jr. ** President & CEO The Academy of Natural Sciences of Drexel University Joseph A. Goldblum President

Provost

Cavan Redmond Partner Zarsy, LLC Samuel V. Rhoads Philadelphia Industrial Development Corporation Robert H. Rock Chairman

Perry A. Lerner

Douglas S. Briggs

Managing Director

Adele K. Schaeffer

Crown Global Insurance Group, LLC

Paul J. Schmitt

James W. Lovett

Novitas Capital

Founder & President PMC Property Group, Inc. Morton Collins, Ph.D.* Managing Partner M. Collins Ventures, LLC Susan B. Dillon, Ph.D. President & CEO Aro Biotherapeutics Co. Brian H. Dovey Partner Domain Associates

MLR Holdings, LLC Gerald B. Rorer

Managing Director Milton S. (Tony) Schneider

Myoderm

Founder and Principal

Susan S. McDonald, Ph.D. Chief Executive Officer NAXION

The Glenville Group, Inc. William A. Slaughter, Esq. Partner

Maida Milone, Esq. President & CEO Pennsylvanians for Modern Courts

Ballard Spahr LLP Judith E. Soltz David V. Wachs

Abraham L. Morris

Daniel H. Wheeler

Operating Partner, Pegasus Capital Advisors

President

President, Rittenhouse Advisors, LLC Albert Ominsky, Esq. Ominsky & Ominsky, P.C.

Member, National Academy of Sciences

Faye Olivieri Kozich Seymour S. Preston, III The Millrace Group Doris Taxin

Executive Vice President

PureSight Advisory, LLC

Ronald Caplan

Chairman, Department of Immunology, St. Jude Children’s Research Hospital

The Honorable Harris N. Hollin

University of Pennsylvania

Elizabeth McKee Anderson

COO

Peter C. Dougherty, Ph.D.

Steven H. Chaffee Professor of Communication, Annenberg School for Communication

Herbert Kean, M.D.

Brind Investments, Inc.

Chairman, Realen Properties

Provost

G-II Equity Investors, Inc.

President

Harold M. Davis

Nobel Laureate in Physiology or Medicine (1996)

Vincent Price, Ph.D.****

MEMBERS

Ira Brind

TRUSTEES EMERITI

Pea Vine Properties Edward Ziff, Ph.D. Professor, Department of Biochemistry and Molecular Pharmacology NYU School of Medicine

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*since June 2017 **served until June 2017 ***since July 2017 ****served until July 2017


Welcome to the Board The Wistar Institute appointed John A. Fry, Morton Collins, Ph.D., and Wendell Pritchett, J.D., Ph.D., to its Board of Trustees.

John A. Fry is the President of Drexel University and the former President of Franklin & Marshall College and the former executive vice president at the University of Pennsylvania. He is also the chairman of the Chamber of Commerce for Greater Philadelphia. Fry has spent his career serving higher-education leadership roles as president, chief executive, chief operating officer, board member, and consultant. Fry will serve on Wistar’s Board of Trustees as one of two representatives of the Academy of Natural Sciences of Drexel University, a requirement of Wistar’s governing documents since it was founded in 1892.

Morton Collins, Ph.D., is the Founder and Managing Partner of M. Collins Ventures, LLC, a venture capital fund focused on therapeutic immunology, ultrafast lasers and quantum computing. Prior to founding M. Collins Ventures, LLC, he was Founder and Managing Partner of Battelle Venture Partners, an early stage venture capital fund focused on intellectual property from Battelle Laboratories and six national Department of Energy laboratories managed by Battelle. Collins is a distinguished life sciences industry leader and venture capitalist who brings his experience merging business, science, technology, and finance to The Wistar Institute.

Wendell Pritchett, J.D., Ph.D., is provost and Presidential Professor of Law and Education at the University of Pennsylvania. He began teaching at Penn in 2002, before serving as chancellor of Rutgers-Camden from 2009-2014. An attorney, legal historian, and education scholar, Pritchett was also the deputy chief of staff and policy director of former Philadelphia Mayor Michael Nutter and went on to work with the School Reform Commission and the Redevelopment Authority of Philadelphia. His judiciousness and academic and political experience will help Wistar’s Board of Trustees navigate governance, define connections to Penn and other higher education institutions and advance innovation for The Wistar Institute.


LEADERSHIP COUNCIL

The Wistar Leadership Council is an advisory group of distinguished individuals who are dedicated to advancing the mission of The Wistar Institute—to solve some of the world’s most challenging and important problems in the fields of cancer, immunology and infectious diseases, and produce groundbreaking advances in world health. Through their philanthropic commitment and advocacy, Council members help provide the resources that enable Wistar to nurture innovative ideas, launch new initiatives and train the next generation of leading scientists. CO-CHAIRS

Max Berger Donna F. Weinraub MEMBERS

Mary E. Bak Jennifer Bellis Felix Chapovsky, M.D. Kenneth J. Davis, Esq. Marc Duey Keith Gaspard

Bruce A. Gillespie Merle Gilmore Carrie Gish Joseph Grusemeyer Scott H. Herbert, M.D. Liza Herzog Larry Hollin Carol G. Huff Sharon Tobin Kestenbaum James C. Li

Michelle Mayer Jennifer Mendel Patrick M. Oates, Ph.D. Louis Padulo, Ph.D. Elizabeth A. Pesce Eric S. Rugart Jim Schaeffer Nicole Dresnin Schaeffer Evan Solomon Lynsie Solomon

Alex Stanbach Greg Stanbach James D. Troyer Aubrey Watkins III, Ph.D. Jamie Leigh Wells, M.D. Jeremiah J. White Jr. James Wistar Craig F. Zappetti, Esq.

L to R: Louis and Katharine Padulo and Eric Rugart; Joy Deibert and Michael Magnatta; Danielle Mayer, Michelle Mayer and Mesfin Tegenu; Kathleen Callan, Jim Troyer, and Lester and Donna Weinraub.

AMBASSADORS The Wistar Ambassadors are bright young leaders and philanthropists (40 years of age and under) who are garnering support and spreading Wistar’s message about bold advances in cancer, immunology and infectious disease research. CHAIR

MEMBERS

Lynsie Solomon

Katie Adams Stephanie Desjardins Ken Greenberg Charles Lentz Alexa Lustig

VICE-CHAIR

Katie Pellecchia

30 // THE WISTAR INSTITUTE

Michael Magnatta Matthew Malinowski Jenny Perkins Eric Allen Smith


A N N UA L G I V I N G

Thank You The Wistar Institute wishes to thank all of our donors who generously invest in our mission to contribute to the prevention and cure of cancer and infectious diseases. Each of the individuals, corporations, and foundations listed below made a gift of $500 or more between January 1 and December 31, 2017. PRESIDENT’S COUNCIL $1,000,000+

VISIONARIES $25,000+

Anonymous

Fred J. Brotherton Charitable Foundation

Mr. and Mrs. Douglas S. Briggs

Mr. and Mrs. Harold M. Davis

Bill and Melinda Gates Foundation

Dr. Susan Dillon and Dr. William Wong

Wellcome Trust

Penny and Robert Fox

ISAAC WISTAR SOCIETY $500,000+ Anonymous The Pew Charitable Trusts Estate of William Boude Smith

CENTENNIAL SOCIETY $100,000+ Dr. Miriam & Sheldon G. Adelson Medical Research Foundation Ellen and Ronald Caplan Susan G. Komen Breast Cancer Foundation The Lenfest Foundation, Inc. Mr. Perry Lerner and Ms. Lenore Steiner Macula Vision Research Foundation Melanoma Research Foundation PTS Foundation

Dr. L. Patrick Gage and Mrs. Irina W. Gage Gray Charitable Trust Innisfree Janssen Biotech, Inc. The Leukemia & Lymphoma Society Christian R. & Mary F. Lindback Foundation

The Jayne Koskinas Ted Giovanis Foundation for Health and Policy Herbert Kean, M.D. and The Honorable Joyce S. Kean Mr. and Mrs. Leonard M. Klehr Martin P. Krasner Maida R. Milone Morgan Lewis LLP Martha and I. Wistar Morris III Mr. and Mrs. Abraham L. Morris Office Depot, Inc. Albert Ominsky, Esquire and Paula Dresnin

Mr. James Lovett and Ms. Robin Halpern

Noreen O’Neill Foundation for Melanoma Research

Susan and Graham McDonald

Mr. and Mrs. Arthur M. Pappas

Pennsylvania Breast Cancer Coalition

The Penn Mutual Life Insurance Company

PNC

Mr. and Mrs. Jeffrey E. Perelman

Helen and David Pudlin

Mr. and Mrs. Robert H. Rock

Mr. and Mrs. Cavan Redmond

Martha W. Rogers Charitable Trust

Mr. and Mrs. Gerald B. Rorer

Mrs. Helene Mae Rosenfeld

Daniel Wheeler and Amy Fox

Emily Brown Shields

GUARANTORS $10,000+

William A. Slaughter, Esq. Ms. Judith Soltz and Mr. Richard S. Belas Mr. James Troyer and Ms. Kathleen Callan

Steve Abramson and Caren Barnet

Dick and Carol Vermeil

Tobin Family Foundation

Mr. David Anderson and Mrs. Elizabeth M. Anderson

Mr. and Mrs. David V. Wachs

PATRONS $50,000+

BNY Mellon Wealth Management

The Honorable Constance H. Williams and Dr. Sankey Williams

W.W. Smith Charitable Trust

American Institute for Cancer Research Nancy Blank Ira Brind and Stacey Spector Brian and Elizabeth Dovey Jane and Joseph Goldblum Ruth and Rick Horowitz Mrs. Diane M. Lafferty Leukemia Research Foundation The McLean Contributionship Melanoma Research Alliance The Philadelphia Foundation

Marsha and Robert Chappell June H. Chern

Mr. and Mrs. Bryan S. Weingarten

Drexel University

PRESIDENT’S SOCIETY INSURERS $5,000+

Mr. and Mrs. Joseph J. Fenkel

Susanna Lachs and Dean Adler

The Anne M. and Philip H. Glatfelter, III Family Foundation

Allied Universal

Mr. and Mrs. Bruce A. Goodman

Buchanan Ingersoll & Rooney PC

Morton Collins, Ph.D.

Marcy Gringlas and Joel Greenberg Dr. and Mrs. Peter Gross

Mr. and Mrs. Max M. Berger Ms. Stacy Chern and Mr. Ty Wu

The Hassel Foundation

Mr. Winston Churchill and Mrs. Ellen Churchill

Inovio Pharmaceuticals, Inc.

Citizens Bank

31 // 2017 ANNUAL REPORT


A N N UA L G I V I N G Mr. and Mrs. Norman Cohn

Mr. Eric Rugart

George and Pooh Gephart

Colonial Consulting, LLC

Mr. and Mrs. James R. Schaeffer

Ms. Merle Gilmore

Mrs. Margaret F. Cristofalo

Ed Sickles Family

Ms. Carrie Gish and Mr. Marc Rockford

John and Rosemary Diederich

Doris R. Taxin

Dr. and Mrs. Alfred E. Goldman

Firstrust Bank

Donna and Lester Weinraub

Mr. and Mrs. Peter Havens

Fisher Scientific Mr. and Mrs. Mark Fishman Mr. James J. Fitzgerald IV

PRESIDENT’S SOCIETY FELLOWS $1,000+

Helen F. Graham Cancer Center at Christiana Care Dr. and Mrs. Scott H. Herbert

GenScript USA Inc.

Active Motif, Inc.

Dr. Liza Herzog and Mr. Paul Curci

Glenmede Investment and Wealth Management

Mr. and Mrs.* William A. Albert

The Honorable and Mrs. Harris N. Hollin

Ms. Mary Rhoads Alexander

Lawrence Hollin

Dr. Jennifer Gross and Mr. Eli Gross

Dr. and Mrs. Steven Altschuler

Mr. and Mrs. Jeffrey Honickman

Mr. Joseph F. Grusemeyer, in memory of Georgianna Smith

Anonymous

Lynne and Harold Honickman

Glen and Cheryl Lewy

Mr. and Mrs.* Mark A. Aronchick

Ms. Anne Humes

Mr. and Mrs. Seymour G. Mandell

The Honorable Michael Baylson and Dr. Francis Baylson

Illumina

NAXION

Ms. Jennifer Faith Bellis

Ken Nimblett, in memory of his husband Rusty Miller

Mr. Peter A. Benoliel and Ms. Willo Carey

Daniel J. Keating Company

Drs. Paul and Bonnie Offit

Mr. Richard Bilotti and Ms. Katherine Hatton

Inés and William Rhoads

Mrs. Ian J. Berg

Ms. Susan Hollenstein and Mr. Howard D. Ross

Joseph Boardman, Esq.

Seymore Rubin

Ms. Ophelia Camina

Mr. and Mrs. Fred Shabel

Mr. Morton R. Branzburg

Mr. Michael Simon

Dr. Catherine Chern and Mr. John Auyeung

Susman Godfrey, L.L.P.

Mr. and Mrs. Matthew Cohen

Willis Towers Watson

Cohen, Placitella, Roth P.C.

Mr. James Wistar and Ms. Patricia Smith

Community College of Philadelphia

PRESIDENT’S SOCIETY DIRECTORS $2,500+

Sandy and Stephen Cozen Cozen O’Connor

Robert and Marta Adelson

Mr. Sheldon Cytron and Mrs. Bonnie Cytron

Ms. Mary E. Bak

Dr. and Mrs. Chi Dang

David and Rhonda Cohen

Mr. Ken Davis and Ms. Susan Charleston

Bruce A. and Gale Gillespie

Ms. Manya S Deehr

Dr. and Mrs. Allan Greenspan

Mr. and Mrs. Marc Duey

Drs. Meenhard and Dorothee Herlyn

Brian and Sherry Effron

Mr. and Mrs. Laurence M Holbert

Mr. and Mrs. Charles Ehlers

Carol and Lawrence Huff

Mrs. Anita Farber

Mr. and Mrs. Ira M. Ingerman

Mr. and Mrs. Howard Fischer

Mr. and Mrs. Richard A. Jacoby

Ms. Nina Fite

Mr. and Mrs. Joseph D. Kestenbaum

The Honorable and Mrs. James J. Fitzgerald III

Dr. and Mrs. Louis Padulo Mr. and Mrs. Timothy P. Pesce Philadelphia Phillies Mrs. Marianne Rhoads Ms. Ann Dee Rome

Mr. and Mrs. Daniel K. Fitzpatrick Flyers Charities Mr. and Mrs. Richard J. Fox Mr. and Mrs. Keith M. Gaspard

32 // THE WISTAR INSTITUTE

Dr. and Mrs. Russel E. Kaufman Ms. Linda Kronfeld Ms. Marilyn Kutler and Dr. Ira Silberman Mr. and Mrs. Tor F. Larson Elizabeth Wistar Little Mr. Ira M. Lubert Mr. Matthew Malinowski and Dr. Charles W. Lentz Mrs. Gerd Maul Ms. Michelle Mayer Jennifer Mendel and Fred Fox Mr. and Mrs. Henry N. Nassau Novak Strategic Advisors Mr. and Mrs. Michael Paul Mr. and Mrs. T. Sergeant Pepper PerformRx Philadelphia FIGHT Pincus Family Foundation Powell Family Foundation Dr. Wendell E. Pritchett and Ms. Anne Kringel Mrs. Diane S. Raynes Mr. William J. Reulbach and Ms. Lisa Bierly Mr. and Mrs. Samuel Vail Rhoads Nancy H. Rhoads and Adam L. Glick Dr. and Mrs. Louis E. Rossman Mr. and Mrs. David Rubenstein Mr. Karl F. Rugart Salveson Stetson Group Mr. and Mrs. Robert Schaeffer Mr. and Mrs. Anthony L. Schaeffer


A N N UA L G I V I N G BENEFACTORS $500+

Mr. and Mrs. Ronald J. Naples

Paul and Sharon Schmitt Dan and Sheila Segal

Mrs. Annette Aerenson

Mr. Frank Seidman

Mr. and Ms. Peter W. Ambler

Kathleen Ellen O’Neill and Joseph S. Zajaczkowski

Mr. and Mrs. Richard Seitchik

Mr. Thomas J. Baldoni

Elaine Shapiro

Charles J. Bauernschmidt

Ms. Naomi Shapiro

Mrs. Laura J. Belman

Mr. and Mrs. Richard Sheerr

Mr. and Mrs. Gerald E. Burns, Esquire

David and Donna Shuey

Sandra and Robert Clapham

Kim and Richard Sichel, in memory of Margaret Leonard Brown

Mrs. Barbara Couphos

Leslye Silver

Mr. Garret and Mrs. Stephanie Desjardins

Mr. Ronald and Dr. Debbie Schiller

Mr. and Mrs. Howard A. Silverman Ms. Margret Skitarelic Mr. and Mrs. Evan Solomon Mr. Larry Spitz and Ms. Carol Klein Mr. Lawrence V. Stein and The Honorable Mary McLaughlin Dr. and Mrs. Matthew Stern Susan R. and John W. Sullivan Foundation TD Bank Mr. Argie Tidmore and Ms. Shelia Monaghan Mr. Joseph Trainor Mrs. Molly C. Turman University City Science Center Dr. Diana Uy Webber Associates Dr. Jamie Leigh Wells Mr. Thomas K. Whitford and Mrs. Margaret B. Lehr Jane and Mark Wilf Ms. Caroline P. Wistar Mr. Gil Wistar Mark Wistar and David Hankins Mr. and Mrs. Caleb C. Wistar The Worsham Family Foundation

Dr. and Mrs. Satish L. Deshmane Ms. Laura E. DiGiambattista Elizabeth and Robert Ervin Mr. and Mrs. Robert T. Forrester Mrs. Linda Frankel Great Valley Field Hockey Ken Greenberg Ms. Anita Groom Ken Greenberg after Great Valley Field Hockey Mr. and Mrs. Henry Hao John G. Harkins, Jr. Dr. Joy Heller Mrs. Janet Kronfeld Mr. and Mrs. Matthew Levitties Dr. and Mrs. Todd M. Lipschultz Alexa Lustig Mr. Mark D. Maggioncalda Ms. Michael Magnatta Gabrielle Mandel Mr. and Mrs. Marshall W. Meyer Mr. and Mrs. John W. Moffat Mr. Lee Molineux Dr. Eleanor M. Murdoch

Faye S. Olivieri

Ms. Katie Pellecchia Ms. Jane Pepper Drs. George C. and Kristine Prendergast Ms. Margaret Quinn Anne Rhoads and Noureddine Melikechi Dr. Caroline S. Rhoads Monette and Fred Robinson Dr. Harry Rosenthal, in Memory of the Rosenthal-Moellerich-Voehl Families Deborah and David Ross Ms. Susan Satkowski Ms. Margot Sklar and Mr. Bret Morris Mr. Eric Allen Smith Mr. Richard D. Smith Ms. Cathi Snyder Mr. and Mrs. Greg Stanbach Drs. Heather Steinman and Christopher Lengner T & N Van Service Mrs. Judith M. Tucker Mr. Jose E. Velez Silva Mr. John Ventura Mr. and Mrs. Charles H. Vetterlein Dr. and Mrs. Aubrey Watkins Charlotte C. Weinberg Dr. and Mrs. David Weiner Mr. and Mrs. Jeremiah J. White Dr. and Mrs. Michael Widlitz Mr. Kevin A. Worsh Drs. William H. and Kathleen E. Wunner Mr. and Mrs. Craig F. Zappetti

Maureen Murphy, Ph.D.

Mr. James Zaleski Mr. and Mrs. Bernard Zolot

*Deceased in 2017

Each of our donors is important to us and we make every effort to follow the donor’s preferences when compiling the annual report list. Gifts mentioned exclude in-kind donations under $1M and pledges. Please notify us of any omissions or errors so we can correct our records. Please contact the Institutional Advancement office at 215-898-3930 or email development@wistar.org.

33 // 2017 ANNUAL REPORT


H E R I TA G E S O C I E T Y

The Wistar Heritage Society recognizes the foresight and generosity of individuals who elect to perpetuate their support of biomedical research by including the Institute in their wills or estate plans. The Wistar Institute appreciatively recognizes these members as of December 31, 2017:

Anonymous Francis X. Bresnan Ira Brind June H. Chern Harold M. Davis Joan M. Farkas Dr. and Mrs. Jerome I. Flicker Robert A. Fox Bruce A. Gillespie Stan and Arlene Ginsburg Family Foundation Dr. and Mrs. Alfred E. Goldman

Mr. and Mrs. Bruce A. Goodman Mr. Joseph F. Grusemeyer, in memory of Georgianna Smith Russel E. Kaufman, M.D. Herbert Kean, M.D. Deborah Komins Evelyn S. Kritchevsky Diane M. Lafferty Glorita P. Maida Mr. and Mrs. Kurtis L. Meyer Ken Nimblett, in memory of his husband Rusty Miller

Joan Newhall* Ms. Rosetta Perno Elizabeth A. and Timothy P. Pesce Seymour S. Preston III and Jean E.H. Preston The Edward and Elsa Rhoads Trust Dr. Harry Rosenthal, in Memory of the Rosenthal-Moellerich-Voehl Families Emily Brown Shields Ed Sickles Family James B. Wistar *Deceased

Visit wistar.plannedgiving.org to learn more about The Wistar Heritage Society and ways to make a planned gift to the Institute.

1894

Illustration of the 1894 Building.

34 // THE WISTAR INSTITUTE


W I S TA R F A M I LY G I F T S

The Wistar Institute was founded in 1892 through a generous gift from Isaac Jones Wistar, a prominent Philadelphia lawyer and former Civil War Brigadier General, in honor of his great uncle, Caspar Wistar, M.D., a respected Philadelphian physician and anatomy professor and the author of the first American textbook on anatomy. Isaac’s and Caspar’s descendants continue to support the Institute to this day. In 2017, the Wistar family descendants celebrated the 300th anniversary of their ancestor Caspar Wistar the Elder’s arrival from Germany to Philadelphia (for a full recap of the Wistar family reunion see page 38). The Wistar Institute gratefully acknowledges the following family members who made contributions in 2017:

Wistar family photo, circa 1856.

1856 Ms. Mary Rhoads Alexander Mr. and Ms. Peter W. Ambler Mr. William Nash Ambler Marion and Frederic Ballard Charles J. Bauernschmidt Mrs. Laura J. Belman Sally and Paul Brooke Emma and Thomas W. Brown Ms. Katharine Brown Mr. Nicholas W. Brown Sandra and Robert Clapham Mrs. Barbara Couphos Mrs. Eleanor M. Cox Elizabeth and Robert Ervin Orawan and Andrew Fisher Mrs. Robert Fisher Mr. Robert W. Fisher

Beth and J. Brooke Gardiner Mr. and Mrs. A. Heathcote Hacker III Ms. Elizabeth F. Hasley Mr. and Mrs. Robert Haynes Mr. and Mrs. Bruce Hotaling Heather and Douglas LaBudde Mrs. Elizabeth Wistar Little Susan and Thomas Lloyd Mr. William M. MacDonald Mr. Albert Michell and Ms. Darien Sutton Mr. and Mrs. James Moore Mrs. James R. Moore Mr. David Marriott Morris Martha and I. Wistar Morris III Mr. and Mrs. Michael M. Mykytiw

35 // 2017 ANNUAL REPORT

Mr. Allen Nicholson and Mrs. Rhonda Nicholson Mr. and Mrs. Phillip M. Nord Ms. Lydia P. Quill Ms. Joan Curtis Reese Anne Rhoads and Noureddine Melikechi Dr. Caroline S. Rhoads Inés and William Rhoads Mrs. Marianne Rhoads Nancy H. Rhoads and Adam L. Glick Mr. and Mrs. Samuel Vail Rhoads Mrs. Joan C. Roberts Gloria Marin Darthea Sharples, Ph.D. Emily Brown Shields Kim and Richard Sichel Mr. and Mrs. Matthew M. C. Smith Mrs. Elizabeth C. Stevenson Mrs. Molly C. Turman Mr. and Mrs. John Weir Mrs. M. Weir Mr. and Mrs. Caleb C. Wistar Ms. Caroline P. Wistar Mr. and Mrs. Charles M. Wistar Mr. Gil Wistar Mr. James B. Wistar Mr. Jonathan M. Wistar Mark Wistar and David Hankins Mr. Stephen Wistar


COMMUNITY ENGAGEMENT & SPECIAL EVENTS

2017 marked a momentous occasion for Wistar—an opportunity to commemorate our legacy and reconnect with our roots as we celebrated a milestone anniversary. In addition to our annual events, Wistar hosted several special events to honor the Institute’s 125th anniversary and express our gratitude to Wistar’s dedicated community of supporters.

Nikon Small World F RIDAY, JAN UARY 1 9 | TH E W I STA R I N STI TUTE For the past 14 years, the international Nikon Small World exhibition has set up home for a short stint at Wistar. More than 180 people attended the opening night reception of the Nikon Small World exhibit, which merges science and photography by showcasing the 20 astounding winning images from the 2017 Nikon Small World Photomicrography Competition. The collection offers a glimpse into a world that most have never seen—the intersection of art and science. Wistar is the only venue in the Philadelphia region to showcase the exhibition.

Guests enjoyed the exhibit, microscopy demonstrations and a talk by Wistar’s Jamie Hayden, managing director of the Imaging facility (below).

Authors Series TH URSDAY, AP RIL 1 3 | TH E W I STA R I N STI TUTE What happens when ideas presented as science lead us in the wrong direction? Paul Offit, M.D., chief of the Division of Infectious Diseases and the director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, shared those “aha” moments via a special presentation at Wistar that featured his newly published book Pandora’s Lab: Seven Stories of Science Gone Wrong.

36 // THE WISTAR INSTITUTE


Philadelphia Science Festival SATU RDAY, AP RIL 2 9 BENJAMIN F RAN KL I N PA R K WAY, P H I L AD E LP H IA, PA. The Philadelphia Science Festival Carnival at the Great Plaza featured more than 175 exhibitors offering non-stop, family-friendly experiments, interactive activities, games and once again Wistar was part of the excitement. Our staff and scientists helped attendees answer the question “What’s Inside Your Cells?” as they took part in a “tasty” experiment to inherit genetic traits and they also learned how cells work to keep us healthy and fight disease.

Wisteria Party WE D N E SDAY, M AY 1 0 | M O R R I S A R B O R E TU M The Wisteria Party, hosted at the Morris Arboretum, appropriately kicked-off the 125th celebrations with an evening among blooming Wisteria, the plant named after Institute namesake Dr. Caspar Wistar. New York Times bestselling author Andrea Wulf provided a talk about her book Founding Gardeners to members of the President’s Society. The Morris Arboretum provided the ideal venue, as it once was a summer home belonging to John and Lydia Morris, relatives of the Wistar family. TOP LEFT L to R: Kate Wunner, , Ph.D., Walter Gerhard, M.D., John Cooke, Esther Gerhard, Jessica Cestone, Ursula Maul, William Wunner, Ph.D. BOTTOM LEFT L to R: Nicole Rhoads, Rive Cadwallader, Alexandra Rhoads, Marianne “Nancy” Rhoads, Sam Rhoads.

TOP RIGHT L to R: Judith Soltz, Jennifer Evans Stacey, Dario Altieri, M.D., Richard Belas, Helen and David Pudlin. BOTTOM RIGHT Andrea Wulf, guest speaker.


COMMUNITY ENGAGEMENT & SPECIAL EVENTS

Wistar Family Reunion F RI DAY, SE P T E MBE R 1 6 TH E WISTAR IN ST IT U TE A N D H I STO R I C S I TE S TH RO U GH OU T T H E PH I L A D E L PH I A R E G I O N The Institute’s 125th birthday coincided with another significant historic anniversary: 300 years from the arrival of the Wistar family’s founding father Caspar Wistar The Elder to the United States from Germany, on Sept. 16, 1717. This occasion drew a large contingent of Wistar family members to the Institute, who gathered for a weekend of Wistar-hosted festivities and events that centered around their heritage and the impact their family had on the Philadelphia region.

James Wistar, co-chair of the Wistar family reunion

William Rhoads

Wistar family members tour historic sites around Philadelphia.

125th Anniversary Gala SATU RDAY, SEP T. 1 7 DILWORTH PA RK, P HIL A DEL P HIA, PA Wistar’s 125th Anniversary Gala was held in the heart of Philadelphia in front of City Hall. More than 400 guests including scientists, donors and friends gathered to commemorate Wistar science and our breakthroughs that impact human health globally. The evening honored Helen P. Pudlin, Esq., chair of Wistar’s Board of Trustees since 2012, with the Wistar Award for her commitment to the Institute and biomedical research. ABOVE L to R: Jenny Perkins, Gianni DiMezza, Lynsie and Evan Solomon, Matthew Malinowski RIGHT MIDDLE L to R: Richard Horowitz, Adele Schaeffer, Helen Pudlin, Dario Altieri, M.D.

38 // THE WISTAR INSTITUTE


Core Day 2017

Laurel Hill Cemetery Tour

TH U RSDAY, SE P T E M B E R 28

THU RSDAY, OCTOBER 1 9

C H ILD RE N ’S H OSP ITA L O F PH I L A D E L PH I A CA M PU S “Combining our resources. Enabling science.” was the theme of this year’s joint Core Fair, held in partnership by Wistar, Children’s Hospital of Philadelphia and the University of Pennsylvania. Attendees visited with more than 50 research core facilities to discuss opportunities to collaborate on research endeavors.

The Laurel Hill Cemetery guided tour brought participants to a National Historic Landmark where several members of the Wistar family and illustrious Philadelphia scientists and physicians are buried. The tour illustrated the historic contributions of these scientists and health care providers over the course of the city’s history.

Wistar at the Mütter Museum

Champion Run for Research

WED N E SDAY, N OVEM B E R 1 5

SU NDAY, NOV EM BER 1 2

The Wistar at the Mütter Museum event wrapped up the 125th special events with a pop-up exhibit of Wistar artifacts at the Mütter, followed by a panel discussion about Philadelphia being the birthplace of American medicine. Speakers included renowned vaccine researcher Dr. Stanley Plotkin, M.D., Wistar Emeritus Professor, and Anna Dhody, Director of the Mütter Institute and Curator of the Mütter Museum, moderated by Wistar’s Anita Pepper, Ph.D.

The Wistar Institute hosted a 2-mile fun run/walk to support Wistar’s research trainees—pre- and postdoctoral research fellows who play an essential role in the transformative research we do every day. In the spirit of this giving season, funds raised from this directly supported the training, education, and development of the next generation of biomedical researchers. The run/walk began at the Institute and ended at the Rocky statue in front of the Philadelphia Museum of Art.

39 // 2017 ANNUAL REPORT


COMMUNITY ENGAGEMENT & SPECIAL EVENTS

Women & Science Program JA N UARY, AP RIL, J U N E , N OV E M B E R 20 1 7 | TH E W I STA R INSTITU TE Wistar’s Women & Science Program features the contributions made by women scientists to biomedical research and raises funds to promote their work. Speakers include Wistar scientists and renowned guest researchers who discuss topics such as cancer, aging, vaccines, immune disorders and allergies, HIV, and infectious diseases.

T HUR S DAY, JA N . 2 6 “What is Aging? An Inside Look at How Cells Change Over Time” by Ashani Weeraratna, Ph.D., associate professor of the Tumor Microenvironment and Metastasis Program at The Wistar Institute.

Ashani Weeraratna, Ph.D.

L to R: Kate O’Neill, Eleanor Murdoch, Ph.D., Eleanor Armstrong.

L to R: Maybeth Christiansen, Nicole Schaeffer, Caroline O’Halloran, Robin Lovett, Sandy Edelstein, Ruth Horowitz, Lisa Schoenber

TH U RSDAY, APRIL 6 Helen D. King Award Ceremony to Recognize Outstanding Women In Biomedical Research HONOREE: Nancy H. Hopkins, Ph.D., The Amgen, Inc. Professor of

Biology Emerita at the Massachusetts Institute of Technology, presented “Cancer Research and Gender Equity: Stunning Progress, a Long Way to Go.” Nancy Hopkins, Ph.D., and Sue Dillon, Ph.D.

L to R: Charles Lentz, Stephanie Desjardins, Katie Pellecchia, Nancy Hopkins, Ph.D., Lynsie Solomon, Matthew Malinowski


TH UR S DAY, J UNE 2 2 “Your DNA: What Does it Mean to Have a Genetic Cancer Mutation and How Does That Inform Cancer Therapy?” by Maureen Murphy, Ph.D., professor and program leader of the Molecular and Cellular Oncogenesis Program, associate vice president for Faculty Affairs, and associate director for Education and Career Development at The Wistar Institute.

L to R: Susan Hoffman, Debra Murphy, Maureen Murphy, Ph.D., Kavitha Sarma, Ph.D., Qing Chen, M.D., Ph.D.

TH U R S DAY, NOV. 2 “A Passion for Prevention: A Journey in HIV, Malaria and Respiratory Viruses” by guest speaker Tonya Villafana, Ph.D., MPH, senior director of product development and team leader of infectious disease at MedImmune.

L to R: Ellen Caplan, Anja Levitties, Anita Pepper, Ph.D., Amy Fox, Jan Erickson, Ph.D.

Tonya Villafana, Ph.D., MPH


2017 FINANCIALS

TOTAL EMPLOYEES (PAID)

PREDOCTORAL FELLOWS

LABS

VISITING SCIENTISTS

POSTDOCTORAL FELLOWS

COUNTRIES REPRESENTED

282

18

34

6

60

25

SOURCE OF FUNDS ● Federal Grant Funding

$40,773,000

40%

● Investment & Other

$23,285,000

23%

● Technology Transfer

$17,427,000

17%

● Foundation & Other Private Funding

$12,822,000

13%

● Corporate-sponsored Research

$3,640,000

4%

● State Funding

$1,401,000

1%

● Unrestricted Contributions

$1,248,000

1%

● Gift-In-Kind

$1,184,000 1%

TOTAL

$101,780,000

USE OF FUNDS ● Direct Research

$47,767,000

66%

● General & Administrative

$10,221,000

14%

$7,211,000

10%

● Operation & Maintenance of Plant:

$5,679,000

8%

● Interest Expense

$1,258,000

2%

● Depreciation/Disposals of Capital Assets

● Pension Losses TOTALS CHANGE IN NET ASSETS

42 // THE WISTAR INSTITUTE

$0 $72,136,000 $29,644,000

0%


2017 PATENTS ISSUED U. S . PAT E N T N o . 9, 5 6 8 , 4 8 6 Methods and Compositions for Diagnosis of Ectopic Pregnancy Issue date: Feb. 14, 2017 Inventors: David Speicher, Lynn Beer U. S . PAT E N T N o . 9, 6 2 4 , 5 1 0 Adenoviral Vectors Comprising Partial Deletions of E3 Issue date: Apr. 18, 2017 Inventors: Hildegund Ertl, Xiang Zhou U. S . PAT E N T N o . 9, 6 7 5 , 6 0 7 Epimorphic Regeneration and Related Hydrogel Delivery Systems Issue date: Jun. 13, 2017 Inventor: Ellen Heber-Katz

Chromatin

U. S . PAT E N T N o . 9,7 2 4 , 3 9 3 Methods and Compositions for Treatment of Metastatic and Refractory Cancers and Tumors Issue date: Aug. 8, 2017 Inventors: JosĂŠ Conejo Garcia, Michael Allegrezza U. S . PAT E N T N o . 9,7 2 4 , 4 0 6 Constructs for Enhancing Immune Responses Issue date: Aug. 8, 2017 Inventors: Hildegund Ertl, Marcio Lasaro U. S . PAT E N T N o . 9,7 4 4 , 2 2 4 Methods and Compositions for Treating or Preventing Cancer Issue date: Aug. 29, 2017 Inventors: Hildegund Ertl, Ying Zhang

The mission of THE WISTAR INSTITUTE is to marshal the talents of outstanding scientists through a highly-enabled culture of biomedical collaboration and innovation, in order to solve some of the world’s most challenging and important problems in the fields of cancer and immunology, and produce groundbreaking advances in world health. Consistent with a pioneering legacy of leadership in not-for-profit biomedical research and a track record of life-saving contributions in immunology and cell biology, The Wistar Institute aims to pursue novel and courageous research paths to life science discovery, and to accelerate/ potentiate the impact of those discoveries by shortening the path from bench to bedside.


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The WISTAR INSTITUTE is an equal opportunity/ affirmative action employer. It is the policy of The Wistar Institute to provide equal employment opportunities to all individuals regardless of race, color, creed, religion, national origin, ancestry, sex, age, veteran status, disability, sexual orientation, gender identity, or on the basis of genetic information, or any other characteristic protected by federal, state, or local law, with respect to all terms and conditions of employment. Š 2018, The Wistar Institute of Anatomy and Biology

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The Wistar Institute Annual Report 2017  

The Wistar Institute Annual Report 2017