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Finding Balance at the Bench

Written by The Wistar Institute on . Posted in Featured News.

This National Postdoc Appreciation Week, we asked our postdoctoral fellows how they strive to keep balance between their research and personal lives.

Wistar postdoctoral fellows serve as critical members of a principal investigator’s lab. They have the opportunity to lead independent projects, delving deeper into scientific questions beyond their Ph.D. degree. Our postdocs are mentored and trained by leading scientists and involved with cutting edge research to prepare them for lasting careers in biomedical research and the life sciences.

Exercise and Other Hobbies

In Wistar’s Ellen and Ronald Caplan Cancer Center, exercise and creative expression keep some of our postdocs balanced.

Dr. Xue Hao in the lab of Rugang Zhang, Ph.D., is currently working on the interplay between tissue aging and cancer and hopes her research can inform strategies to promote healthy aging and combat cancer.

She shares, “I always try to find some ‘me time’ to balance the intensity of bench work. I am a strong believer in daily exercise and good sleep to help me stay positive and energized. I also enjoy listening to classical music, sketching, and cooking.” Hao also enjoys watching tennis games, inspired by the champion players and their mental fortitude to help her overcome challenges in her life.

Exploring Beyond the Lab

In the Vaccine and Immunotherapy Center of the Institute, some postdocs turn to travel and exploration of the world around them to find their balance.

Dr. Maria Belen Palacio in the lab of Amelia Escolano, Ph.D., develops new models to address challenging immunology questions in vaccine design and infectious diseases. Originally from a small town called Metán in the northwest corner of Argentina, Palacio is the second eldest of four siblings and spent her spare time during her college years visiting her large family. Now 7,000 kilometers away from them, she has taken this time to engage with the new environment in which she now lives.

She explains, “Whenever I feel stressed, my family is my strongest support. I also like running and outdoor activities. Since I am new to the U.S. and to Philly, I really enjoy exploring new areas of the city and traveling to nearby places.”

Blue and green banner for The Wistar Institute's Women & Science Program series with a photo of Dr. Elizabeth Jaffee

Setting a Prime Example: Wistar’s Women & Science Program featuring Dr. Elizabeth Jaffee

Written by The Wistar Institute on . Posted in Featured News.

As attendees tuned into their screens, Dr. Elizabeth Jaffee began her presentation Pancreatic Cancer Is PRIMED to Become an Immunologic Disease. With a full house of Zoomers, the Deputy Director of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins School of Medicine discussed her cutting-edge research to develop immune-based therapies for pancreatic cancer at Wistar’s most recent Women & Science event.

Jaffee’s passion for science began with her inspirational 4th grade math teacher and later in her youth by reading Marie Curie’s biography. The seemingly endless scientific opportunities of the early days of the U.S.’s space race also played a role in her career choice. “I think today is just like when I was growing up – the opportunities in science are endless, particularly in biomedical research with the recent technological revolution. It’s a very exciting time in history.”

During her college years, Jaffee became increasingly focused on vaccines, which led to her current work developing pancreatic cancer treatments. She explains that with a high recurrence rate, increasing mortality, late diagnosis with no specific early symptoms, and high-risk populations, pancreatic cancer is an ideal model for studying immune resistance.

Jaffee developed a vaccine that operates by inserting a gene into tumor cells to express signals that attract the immune system and induce a response from T cells. However, tumors protect themselves from the immune system by inactivating T cell response. Antibodies can be designed to enhance a suppressed T cell response, and thus underpins the second step in Jaffee’s emerging immunotherapy strategy. By first inducing T cell activity with vaccines and then optimizing T cell function with antibodies, Jaffee hopes to intercept and eliminate cancers at the earliest stage before they develop immune resistance.

With the advancement of molecular and sequencing technologies, Jaffee is looking at developing immunotherapies specific to cancer patients. “We are at a time where we can personalize treatments for patients,” she shared.

Dr. Jaffee earned her M.D. from New York Medical College. She is currently a principal investigator at John Hopkins University, chair of President Biden’s Presidential Cancer Advisory Panel, and holds six vaccine patents. The presentation concluded with a Q&A session led by Amelia Escolano, Ph.D. and Jessie Villanueva, Ph.D., the scientific advisors for the Women & Science program.

Learn more about Wistar’s Women & Science Program.

3D rendering of PD-1 and PD-1L protein molecules on t cell and cancer cells binding as part of a immune checkpoint

Wistar Scientists Identify Key Biomarkers that Reliably Predict Response to Immune Checkpoint Inhibitor Therapy for Melanoma

Written by The Wistar Institute on . Posted in Press Releases.

New research finds biological processes that improve prediction of therapeutic performance and provide a framework to develop predictors for this aggressive skin cancer.

PHILADELPHIA — (SEPTEMBER 19, 2022) — Immune checkpoint inhibitor (ICI) therapy is a type of treatment for melanoma, the deadliest form of skin cancer, which blocks proteins on tumor or immune cells that prevent the immune system from killing cancer cells. While this treatment has shown some clinical success in patients with advanced stages of melanoma, its efficacy depends on reliable predictors of a patient’s response to the therapy. Currently, the only FDA approved biomarker for ICI melanoma treatment is the tumor mutation burden assay, ¬but the mechanisms linking it to ICI remain unclear. However, new research now provides evidence of novel, reliable biomarkers that predict therapy response using advanced computer technology.

In a paper published in Nature Communications, Noam Auslander, Ph.D., assistant professor in the Molecular & Cellular Oncogenesis Program of Wistar’s Ellen and Ronald Caplan Cancer Center, and Andrew Patterson, graduate student in the Auslander lab, identify novel predictors of ICI therapy for melanoma. In particular, mutations in the processes of leukocyte and T-cell proliferation regulation show potential as biomarkers with reliable and stable prediction of ICI therapy response across multiple different datasets of melanoma patients.

“This work aims to identify better and more biologically interpretable genomic predictors for immunotherapy responses,” notes Auslander. “We need better biomarkers to help select patients that are more likely to respond to ICI therapy and understand what factors can help to enhance responses and increase those numbers.”

Using machine learning and publicly available de-identified clinical data, researchers investigated why some melanoma patients responded to ICI therapy and others did not. Patterson, first author on the paper, details that their research process involved training machine learning models on a dataset to predict whether a patient responds to ICI therapy, and then confirming that the model was able to continually predict response or resistance to this treatment over multiple other datasets.

The team found that leukocyte and T-cell proliferation regulation processes have some mutated genes that contribute to ICI treatment response and resistance. This knowledge could be used to identify targets to enhance responses or mitigate resistance in patients with melanoma.

“We were able to better predict if a patient would respond to ICI therapy than the current clinical standard method as well as extract biological information that could help in further understanding the mechanisms behind ICI therapy response and resistance.” Patterson explains.

The scientists intend to continue this work with the goals of increasing prediction accuracy, further understanding biological mechanisms underpinning patient resistance or responsiveness to ICI therapy, and determining whether the processes distinguished in the paper can also serve as predictors of ICI treatment response for other cancer types.

Co-author: Andrew Patterson

Work supported by: The results shown here are in whole or part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. The research reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under Awards R00 CA252025 and P50 CA174523.

Publication Information: Mutated Processes Predict Immune Checkpoint Inhibitor Therapy Benefit in Metastatic Melanoma. Nature Communications, 2022. Online publication.

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The Wistar Institute marshals the talents of an international team of outstanding scientists through a highly-enabled culture of biomedical collaboration and innovation, to solve some of the world’s most challenging and important problems in the field of cancer, immunology, and infectious diseases, 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, Wistar scientists pursue novel and courageous research paths to life science discovery, and to accelerate the impact of early-stage discoveries by shortening the path from bench to bedside.

Unraveling The Enigmas of Melanoma

Written by The Wistar Institute on . Posted in Featured News.

Meenhard Herlyn, D.V.M., D.Sc., is known internationally as one of the fathers of melanoma research. As the founder of The Wistar Institute Melanoma Research Center, he has led the way with breakthrough discoveries about this mysterious and hard-to-treat cancer. A highlight of his work includes building Wistar’s collection of patient-derived xenografts — a groundbreaking tool that allows tumor cells to be implanted into models for melanoma research.

Now, a new generation of melanoma researchers are building on that foundation. This up-and coming-scientific force includes Chengyu Liang, M.D., Ph.D., a rising star in studying how UV exposure damages cells.

“Dr. Herlyn is a great mentor and a great scientist,” Liang said. “He established the platform, the foundation, that has been indispensable not only for Wistar melanoma research, but for the entire melanoma research field.”

BUILDING A BETTER MODEL

“One of the guiding forces in our research has been to mimic human disease, to figure out what makes cells become cancer, and to use this knowledge for new strategies to develop therapies,” Herlyn said.

One of these strategies involves the use of artificial skin. Lab-grown skin had previously been developed for wound healing. Using this existing technology, Herlyn pioneered its application to melanoma research. Herlyn’s team was the first to use artificial skin to grow and study melanocytes — normal pigment cells — which they have used to understand how cancer cells form and how to make treatment more effective.

“We wanted to really know what tumor cells do, and to understand that, we first need to know what normal cells do and where the tumor cells come from,” he explained.

Herlyn joined Wistar in 1976 and spent the early years of his career focused on developing monoclonal antibody treatments, a breakthrough drug that mimics or enhances the immune system’s natural disease fighting activity to attack cancer cells.

One of Herlyn’s frequent collaborators during this time was his wife, Wistar scientist Dr. Dorothee Herlyn, who is now retired. “She was the immunologist of the family,” he said. Together, they helped develop a number of monoclonal antibody molecules, some of which are still used in cancer therapies today.

Herlyn is also behind Wistar’s patient-derived xenograft program which supports a collection of patient cancer tissues. These samples can be implanted into genetically altered mice to more closely mimic conditions in the human body. It’s a powerful tool scientists can use to conduct cancer experiments and test new treatments under conditions that more closely mimic the disease in humans.

“We now have more than 500 tumors from patients,” Herlyn said. “These come directly from the patient and are implanted without ever being cultured, making them much more like real life tumors.”

THE “SUNSCREEN GENE” AND MELANOMA

Dr. Liang didn’t set out to study melanoma. Originally trained as a medical doctor, she became a research scientist with the mission of improving patient outcomes. Her drive to understand cancer and develop better treatments became more personal after her mother passed away following a two-year battle with cancer.

“When someone you love has cancer, you’re trying to find answers. Why did this person have cancer? Why is this treatment not helping?” she said. “Eventually, that drove me to get my Ph.D. in medical science. I wanted to know more.”

Liang initially focused her research on tumor virology, studying how viruses cause cancer. During her research, she encountered a gene called UVRAG that piqued her interest in melanoma.

Previous work had found that this gene seemed to be involved in protecting skin cells from UV radiation, but the mechanism behind it was unclear. Liang’s team showed how the gene repaired DNA damage from UV radiation, and that disrupting the gene could increase a person’s risk of melanoma and other skin cancers. They nicknamed UVRAG the “sunscreen gene.”

The finding sparked many questions about how UV radiation causes genetic mutations that lead to cancer. “The question we asked is, ‘What makes melanoma melanoma?’” she said.

One thing that sets melanoma apart is its extremely high rate of genetic mutations — much higher than other cancers. “It’s in the skin, which is where the body interconnects with the environment and UV radiation, so in a way, that’s not surprising,” she explained.

Liang’s recent research has focused on identifying signs of DNA-repair deficiency as an early sign of damage that can trigger melanoma-driving mutations. “If we can find genetic signs that can predict this process, we might be able to catch the disease much earlier,” she noted.

CULTURING COLLABORATION

Herlyn not only laid the groundwork for Liang and fellow cancer researchers. He also serves as a leader and mentor who is generous with his knowledge and support, Liang said. “He’s like a big dictionary of melanoma,” she described. “When you have a question, he can always share something instructive.”

This philosophy of collaboration, Herlyn shared, has been a driving force in his work. “One of the major strengths at Wistar has been our flexibility and our ability to look for collaborators,” he pointed out. “My approach has always been to look for the best people I could work with.”

This has included a longtime collaboration with oncologists, pathologists, and other clinical colleagues at the University of Pennsylvania as well as other institutions. “I’ve always believed strongly in a good connection between the laboratory and the clinician,” he said.

Herlyn also helped found the Society for Melanoma Research, the first ever medical conference dedicated to bringing together researchers, clinicians, and patients to share knowledge about melanoma. Liang emphasized that with such a complex and unique disease, it’s critical for scientists to work together to find new diagnostic tools and treatments.

“There’s still a lot of mystery,” she stated. “Despite all the tremendous progress we have made in the melanoma field, I think we are still at the tip of the iceberg.”

Career Spotlight: Carlos Carmona in the Montaner Lab

Written by The Wistar Institute on . Posted in Featured News.

Recently, The Wistar Institute created a virtual tour of our Montaner Lab which focuses on infectious disease research such as HIV through highly collaborative regional and international projects. We interviewed Carlos Carmona, Data and System Manager for the team. Read more about how he got to where he is now, and a glimpse inside working in the Montaner Lab at Wistar.

What is your personal story, journey to science, and future goals?

My career story is not as clear cut as some may expect. In college, I studied public health, where I wanted to understand and promote the health and well-being of all people. From mapping out how diseases spread to launching initiatives that keep communities healthy, public health touches almost everything you can imagine. As a first-generation Latino college graduate from North Philly, it was quite daunting trying to navigate my options and find a place where I can make an impact in my city.

Then, I stumbled upon data. Before working at Wistar, I had been in research projects that always asked how data was collected and how that led to results. It was interesting to experience how reviewing information from Excel sheets and building data visuals can impact our understanding of the world, especially in biomedical research.

What is your current position and how do you collaborate with each other and other lab members?

As a Data and System Manager, I can piece together reports that not only help clinical teams troubleshoot data issues, but also understand their study participants better as they go through clinical trials. I also get the opportunity to contribute to research discussions about efficient data collection methods and leveraging data to make a measurable impact where it counts.

What were the scientific goals you most want to accomplish in your Wistar work related to your MPH degree? What are your goals beyond?

Like my experience in public health, working in data means wearing many hats. You’re a translator, team player, problem solver, and trailblazer all at once. My biggest goal at Wistar is taking pieces of data from our research studies and communicating how that data is a steppingstone toward building a healthier life for everyone. And I get to do that one report at a time!

Unraveling the Ties That Bind: Epstein-Barr Virus and Multiple Sclerosis

Written by The Wistar Institute on . Posted in Featured News.

A conversation with the Lieberman Lab delves into how EBV can trigger MS and potential therapeutic solutions that can be developed with this knowledge.

Epstein-Barr virus (EBV) is ubiquitous, establishing lifelong infection found throughout the world. It targets the immune system’s B cells and typically remains silent in immune system memory cells. Though infection with the virus is largely asymptomatic, specific biological and environmental conditions can enable the virus to cause more serious diseases. For instance, the virus can cause rare cancers that occur at much higher rates in immunosuppressed individuals. More recent research has found a connection between EBV and the neurodegenerative disease, multiple sclerosis (MS).

In a recent article published in Nature Reviews Microbiology, Paul Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor; program leader, Gene Expression & Regulation Program, Ellen and Ronald Caplan Cancer Center; and director, Center for Chemical Biology & Translational Medicine; and Samantha Soldan, Ph.D., staff scientist in the Lieberman laboratory, review evidence of EBV as a cause of MS and the implications of this knowledge in research and clinical spheres.

“Eliminating EBV latent infection should be a safe and effective way to treat EBV cancers and autoimmune disease, especially multiple sclerosis,” Lieberman says.

We spoke with Soldan about the link between EBV and MS as well as how this knowledge can be harnessed into potential therapeutics for the disease.

Q: What is some of the background linking EBV to cancer?

A: EBV was the first virus to be implicated as a causative agent of human cancer. EBV has been linked to nasopharyngeal cancers, stomach cancers, primary CNS lymphomas, Hodgkin’s and non-Hodgkin’s lymphomas, NK/T-cell lymphomas, and leiomyosarcomas, as well as several autoimmune disorders, including MS. It is currently estimated that 1.5-2% of all human cancers are attributable to EBV infection. All EBV-related cancers are associated with latent infection, where no infectious virus is produced by the tumor cells. Different types of EBV-associated cancers express different EBV latency genes. Notably, all EBV cancers express the viral protein EBNA1—required to maintain the EBV genome in latently infected cells and a primary interest of the Lieberman lab.

Q: What inspired this review to investigate evidence behind EBV as a cause of MS?

A: The case for EBV as a causative agent in MS has been mounting over the last 40 years. This year, two landmark studies were published: one providing a strong epidemiologic link to MS and the other suggesting a mechanism by which EBV may drive disease pathogenesis. These two studies have intensified the MS community’s interest in the link between EBV and MS, both as a disease trigger and as a potential driver of disease pathogenesis.

Dr. Paul Lieberman is a leading expert in EBV and in the study of EBV EBNA1 specifically, and he was invited to write a review article focused on the role of EBV in MS for Nature Reviews Microbiology. Paul asked me to be a co-author for this manuscript and I was delighted to have this opportunity. My background is in neurovirology, and I have been involved in research investigating the relationship between viruses and neuroinflammatory diseases, including MS, since graduate school. I am deeply invested in trying to better understand the role that EBV plays in MS.

Q: Why is multiple sclerosis a complex disease to study?

A: Multiple sclerosis is the most common demyelinating disorder of young adults, effecting more than one million individuals in the U.S. alone. MS is a heterogenous and often disabling disease that develops because of the interplay between the immune system and the environment in genetically susceptible individuals. The clinical progression of MS is variable and unpredictable with several distinct disease courses. In addition, MS patients often transition from a relapsing-remitting to a progressive disease course over time and the mechanism of the disease and central nervous system damage also evolve, which are a hallmark of MS.

Further complicating matters, epidemiological studies have shown that environmental factors (including EBV infection) that contribute to one’s risk of developing MS often occur many years before clinical onset. Collectively, these complex interactions between genetic, immunologic, and environmental risk factors makes attributing disease-contributing agents and designing preventative measures and effective therapies for MS very challenging.

Q: How does EBV trigger MS? Can you explain these processes?

A: How a ubiquitous agent like EBV triggers disease in a small percentage of those who are infected is an enigma. We face this challenge in understanding the role of EBV in cancer as well as MS. For MS and many autoimmune diseases, we can identify inflammatory and autoreactive immune responses and characterize immune responses to infectious agents and antigens that trigger immune response in patients. However, understanding what set immune cells on an autoreactive and inflammatory path before the patient is symptomatic is a difficult task.

Nevertheless, there are several theories as to how EBV may be both a trigger and a driver of MS and we discuss these in the review. We believe that it is likely that EBV is involved in the pathogenesis of MS at many levels and in different anatomic compartments.

Q: What are some potential therapies that could arise out of understanding the role of EBV in MS?

A: In recent years, therapies depleting B-cells have proven to be tremendously beneficial in MS. While EBV primarily infects B-cells, these B-cell depletion therapies eliminate cells regardless of whether they are infected by EBV, making it difficult to determine if any of the clinical benefit derived from these drugs is related to their effects on the virus.

There are several EBV specific therapies in development that have the potential to present new, effective options for patients with MS. In addition, they may also help us better understand the role of EBV as a trigger and driver of disease pathogenesis. These include vaccines to prevent the development of infectious mononucleosis, MS, and EBV-associated cancers; cell-based immunotherapies, including EBV-specific cytotoxic T cell lines; and EBV specific antivirals.

Q: Why is it important to review existing literature and reveal new directions for research?

A: I find review articles to be incredibly helpful, both to the writer and the reader. When writing a review, you must commit time and energy to refamiliarizing yourself with the latest literature as well as the history of the field. The process helps you take the proverbial 30,000-foot view and see the whole picture, forcing you to get your head out of the specific aspect of research that you are generally focused on and enabling you to generate new ideas and consider new approaches to your work. Reviews are also very important for colleagues and especially trainees to get perspective on where the field is headed and where there are gaps in our knowledge.

Q: What do you currently work on with Dr. Lieberman regarding MS and EBV and where is your research headed?

A: We are working in several directions to better understand the role that that EBV plays in the pathogenesis of MS. Our current work focuses on characterizing virus-host interactions and maintenance of EBV latency in EBV infected B-cells from MS patients compared to healthy controls. Dr. Chenhe Su, a postdoctoral fellow in the Lieberman lab, is also working very hard on these studies.

I am especially interested in developing better animal models to understand how host factors like age of exposure, genetic background, metabolism, and sex influence host-virus interactions and EBV reprogramming of B-cells. We are also testing EBV-specific antiviral therapies, including the EBNA1 inhibitor developed in the Lieberman lab, to determine its potential as a therapeutic agent for use in MS.

Exceptional Wistar Trainees Honored at 2022 Rugart Family Awards Ceremony

Written by The Wistar Institute on . Posted in Featured News.

Dr. Laura Garcia Gerique, postdoctoral fellow in the Nefedova lab, and Sarah Offley, graduate student in Gardini lab, are winners of the 2022 Annual Rugart Family Awards.

This annual event, sponsored by the Rugart Family honors the late Karl F. Rugart, Jr., an obstetrics and gynecology physician and longtime supporter of Wistar. The award is given annually for the best Research-in-Progress presentation by a predoctoral student and postdoctoral fellow.

Postdoctoral fellow Dr. Laura Garcia Gerique presented her work on the role of Annexin A1 protein in tumor biology and how it may impact cancer development, metastasis, and treatment. The second winner, graduate student Sarah Offley focuses her research on characterizing a novel integrator complex subunit that has implications for cancer and disease research.

Since 2014, the Rugart Family Awards recognizes promising early-career scientists demonstrating exceptional presentations of their scientific projects. The winners are voted on by their peers, setting the Rugart Family Awards apart as a unique distinction defined by the competitive, yet collaborative, nature of Wistar’s trainees as they present ongoing research and improve their work.

Wistar Scientists Find Gut Microbe Byproduct Drives Antitumor Immunity

Written by The Wistar Institute on . Posted in Featured News.

The team identified the metabolite TMAO drives immune activation in the tumor microenvironment and boosts response to immune checkpoint blockade therapy in pancreatic cancer.

Rahul S. Shinde, D.V.M., Ph.D., Assistant Professor in the Immunology, Microenvironment, and Metastasis Program of Wistar’s Ellen and Ronald Caplan Cancer Center and the Institute’s inaugural Caspar Wistar Fellow published evidence in Science Immunology of a therapeutic target in the gut microbiome for pancreatic cancer.

Recently awarded the Pancreatic Cancer Action Network Career Development Award, Shinde focuses his research efforts on understanding the gut microbiome and identifying potential targets for cancer therapies. In this newly published paper, Shinde and his collaborators reveal that a metabolite derived from a gut microbe called trimethylamine N-oxide (abbreviated TMAO) boosts immunity against tumors by triggering immune activation in pancreatic cancer. Furthermore, the study provides evidence that targeting TMAO production in the gut microbiome could improve the efficacy of immune checkpoint blockade (ICB) therapy for the disease.

Pancreatic cancer is a particularly deadly disease with a tumor microenvironment that aggressively suppresses immune response. Immunotherapies can be improved by boosting immune activation in the tumor microenvironment – a function influenced by the gut microbiome. In the study, the researchers administered TMAO and observed effects on tumor growth and immune response in the tumor microenvironment. They found evidence that TMAO stimulated action from immune cells such as macrophages and T cells as well as increased pancreatic cancer’s responsiveness to ICB therapy, ultimately boosting the body’s ability to identify and attack cancer cells.

“With growing interest in selective targeting of the gut microbiome to improve cancer treatments, this study can create a new paradigm for discovering novel gut microbial metabolites influencing anti-tumor immunity and inform innovative treatment strategies for highly lethal and hard-to-treat pancreatic cancer,” says Shinde, corresponding author on the paper.

He elaborates that his findings raise a series of questions with clinical implications, including what sources of TMAO confer its anti-tumor effects and whether this beneficial TMAO can be achieved by altering these sources. Additionally, he emphasizes that potential future directions of this work could delve into understanding whether TMAO can promote anti-tumor immunity in other cancer types with treatment resistance.

Shinde collaborated with fellow Wistar principal investigators Chi Van Dang, M.D., Ph.D., Aaron Goldman Ph.D., Hsin-Yao Tang Ph.D., Noam Auslander, Ph.D., Mohamed Abdel-Mohsen, Ph.D., and Andrew Kossenkov, Ph.D. on this study.

This work was generously supported by the following: NIH, the W. W. Smith Charitable Trust, 2022 Pancreatic Cancer Action Network Career Development Award, Grant Number “22-20-SHIN,”, the Tobin-Kestenbaum families, as well as the Caspar Wistar Fellowship Program at The Wistar Institute.

Michele Schiavoni poses for the camera at the Wistar office

The Wistar Institute Welcomes Michele A. Schiavoni, New Vice President of Communications & Marketing

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA—(September 8, 2022)—The Wistar Institute is pleased to announce the appointment of Michele A. Schiavoni, M.S., as Vice President of Communications & Marketing, in a central leadership role that will bolster the visibility of the Institute’s ambitious biomedical research science initiatives and programs advancing the organization’s newly launched Bold Science // Global Impact Capital Campaign.

“I am delighted to welcome Michele to Wistar,” said Dario C. Altieri, M.D., Wistar president & CEO, director of the Ellen and Ronald Caplan Cancer Center, and Robert and Penny Fox Distinguished Professor, “Michele’s leadership will be critical to implementing an integrated communications strategy fluidly aligning priorities as we grow and advance our science and the needs of the Institute. Her knowledge and strong communications experience will be a vital component to the ongoing success of Wistar’s strategic goals.”

A longtime communications executive, Schiavoni brings decades of expertise in building brands for health care systems, nonprofit social services entities, and economic development organizations. Collaborating closely with scientists and administrative leaders, she will oversee marketing and brand strategy across the Institute to coordinate internal and external messaging and reinforce Wistar’s growth trajectory supporting the Institute’s goals and mission. She will also provide strategic communications guidance to the president & CEO.

“It is a privilege to become a part of the Wistar team — Wistar science has a remarkable history of breakthrough research discoveries and developing innovative technologies that have a global impact saving lives,” said Schiavoni. “Wistar scientists continue creating transformative advances in cancer care and infectious disease research. Their latest Capital Campaign supports a bold growth strategy to recruit more scientists to advance international collaboration as well as play a leadership role training the next generation of scientists. I look forward to collaborating with the Wistar team during this exciting time in the organization’s growth.”

Schiavoni joins Wistar from the Delaware Prosperity Partnership, where she served as vice president for external relations and led marketing and communications for Delaware’s lead economic development organization. She previously held communication leadership positions at Elwyn Foundation and ChristianaCare Health System. Schiavoni received a B.A. in communications from the University of Delaware and a M.S. in management communications from Syracuse University, Newhouse School of Public Communication. She also serves as president of the Board of the Tilton Society of Delaware.

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The Wistar Institute is an international leader in biomedical research with special cancer, immunology, infectious disease research, and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.

A cancer cell divides

The Wistar Institute and Jubilant Therapeutics Inc. Find PAD4 Inhibition in Neutrophils Halts Cancer Progression and Metastasis

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA — (Sept. 7, 2022) — Researchers in the laboratory of Yulia Nefedova, M.D., Ph.D., at The Wistar Institute and collaborators at Jubilant Therapeutics Inc. have uncovered a novel mechanism by which protein arginine deiminase 4 (PAD4) in neutrophils promotes cancer progression. The paper also found that inhibition of this function of PAD4 reduces primary tumor growth and metastasis and enhances checkpoint inhibitor treatments. Jubilant Therapeutics Inc. is developing a novel small molecule PAD4 inhibitor that directly targets this mechanism. The findings appear in Cancer Research, a journal of the American Association for Cancer Research.

“Development of metastases remains a leading cause of death from cancer. Tumor-associated neutrophils have long been implicated in cancer progression. Understanding the mechanisms by which these cells promote tumor growth and metastatic spread is critically important for the development of new treatments,” shares Yulia Nefedova, M.D., Ph.D., associate professor, Immunology, Microenvironment & Metastasis Program, Ellen and Ronald Caplan Cancer Center of The Wistar Institute.

This research revealed the importance of PAD4 protein in the migration of neutrophils, specialized white blood cells that serve as the first line of immune defense in the body, directly impacting both primary tumor growth and secondary malignant tumor spread. Both genetic deletion of PAD4 and pharmacological inhibition of PAD4 using Jubilant Therapeutic Inc’s novel inhibitor dramatically down-regulated chemokine CXCR2, reduced immune suppressive polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) at tumor and metastatic sites, activated T cells, and synergized with immune checkpoint blockade.

All results point to a potent anti-tumor effect of PAD4 inhibition to target PMN-MDSCs in the tumor microenvironment. This finding is being further investigated in Wistar’s Nefedova laboratory.

“These results highlight the potential of PAD4 inhibition as a novel treatment approach for cancer in addition to the previously established role of this pathway in autoimmune diseases,” said Luca Rastelli, Ph.D., Chief Scientific Officer, Jubilant Therapeutics Inc. “We are developing several highly selective oral, small molecule PAD4 inhibitors, with the goal of bringing this novel mechanism to the clinic as potential therapeutics for tumor metastasis in colorectal and pancreatic cancers, patients with liver metastasis as well as for both acute and chronic autoimmune/inflammatory diseases.”

These findings were only made possible through the supportive collaboration between Wistar, a Philadelphia based nonprofit biomedical research institute, and Jubilant Therapeutics Inc., a clinical-stage precision therapy company developing new therapies to treat oncology and autoimmune disease.

“Only working together are we able to efficiently translate our fundamental research discoveries into clinical realities,” states Heather Steinman, Ph.D., MBA, The Wistar Institute vice president for Business Development & executive director of Technology Transfer.

Co-authors: Hui Deng, Cindy Lin, Laura Garcia-Gerique, Shuyu Fu, Zachary Cruz, Erin Bonner Matthew Rosenwasser, Sridharan Rajagopal, M. Naveen Sadhu, Chandru Gajendran, Mohd Zainuddin, Ramachandraiah Gosu, Dhanalakshmi Sivanandhan, Miriam A. Shelef, Brian Nam, Dan T. Vogl, and Dmitry I. Gabrilovich.

Publication Information: Regulation of tumor progression by PAD4-mediated neutrophil migration and its targeting with a novel selective inhibitor JBI-589. Cancer Research, 2022. Online publication.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. Wistar’s Business Development Team is dedicated to advancing Wistar Science and Technology Development through creative partnerships. wistar.org.

Jubilant Therapeutics Inc. is a clinical stage precision therapeutics company advancing potent and selective small molecule modulators to address unmet medical needs in oncology and autoimmune diseases. Its advanced discovery engine integrates structure-based design and computational algorithms to discover and develop novel, precision therapeutics against both first-in-class and validated but intractable targets in genetically defined patient populations. The Company’s advanced pipeline consists of a first in class dual epigenetic modifier, JBI-802, currently in a Phase I/II clinical trial to treat solid tumors, a novel brain-penetrant modulator of PRMT5 for which an IND has been accepted, a brain penetrant PDL1 inhibitor, as well as PAD4 inhibitors for oncology and inflammatory indications. The Company is headquartered in Bedminster, New Jersey and guided by globally renowned key opinion leaders and scientific advisory board members. For more: https://www.jubilanttx.com/