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Pancreatic Cancer Survivor and Pancreatic Cancer Advocate Meet Wistar Scientist Focused on Research Advances

Wistar’s Dr. Rahul Shinde with PanCAN’s Nick Pifani and Bruce Platt Rally Around Common Bond

Meet Nick Pifani who came to Wistar to share his story of surviving pancreatic cancer; he was one of several in his family who faced pancreatic cancer and won the battle. Bruce Platt, PanCAN volunteer advisory board member, lost his mother to pancreatic cancer. Nick and Bruce met Wistar’s Dr. Rahul Shinde, a 2022 PanCAN Career Development Award recipient, to learn more about his promising pancreatic cancer research.

“We want to tell the great stories—about the doctors that save lives and the researchers that ultimately bring new drugs, therapies and standards of care to patients,” said Nick. “We also want to tell positive stories of survival.”

Nick and Bruce are Philadelphia ambassadors for the local PanCAN cause, they connect cancer survivors with resources while building awareness and understanding. Pifani and Platt both see the need for a paradigm shift on how patients process a pancreatic cancer diagnosis as well as help the public to understand that pancreatic cancer can be treated effectively.

“My mother was diagnosed in 2004. I became a caregiver in 2006. She passed in 2009—she almost made five years,” said Bruce. “Back then, there were no real treatment options. The doctor basically said to my mother, ‘Go get your affairs in order,’—can you imagine the shock of that?”

When Bruce’s mother passed, he wanted to be her voice and in 2010 went to his first PanCAN meeting. Every year he’s become more involved. Bruce’s passion for the cause led to political action and making headway on pancreatic cancer awareness and support with legislators like Congressman Brendan Boyle and U.S. Senator Bob Casey. Along the way Bruce met many people diagnosed and fighting pancreatic cancer who ultimately became his friends. “I’ve met and become close to amazing people, but you can also get to a point where you think, I’ve done everything I can do. But if I ever get near that point, someone usually calls me and says, ‘So-and-so has it’ and it pumps me back up. So, I go back and fight some more. I’m in this until the day I die.”

When Nick was diagnosed with pancreatic cancer he wasn’t interested in the standard of care. “I knew what the standard of care did for about everybody else and I didn’t want to go down that route because I knew where it would end. Fortunately for me, I had doctors who found genetic mutations and understood I would have better success with different types of chemotherapy and radiation.”

Nick’s hope is that research and treatments progress to where a person diagnosed with pancreatic cancer has more options. “The disbelief and horror that happens when you are diagnosed, will be followed with, ‘We have four different treatment options, they’re effective and have an 80% or 90% cure rate. Which flavor do you want?’ Hopefully, Bruce and I will be around to see that.”

That day isn’t here yet, but Wistar scientists are working to make it happen. Nick and Bruce met with Dr. Rahul Shinde, one of Wistar’s resident pancreatic cancer researchers.

Dr. Shinde’s research is in one of the hottest areas of science and focuses on how the gut microbiome impacts immune cell function — those immune cells’ ability to fight cancer. He hopes to pave the way for future gut-bacteria-based therapies in the hopes of improved pancreatic cancer patient survival.

Dr. Shinde studies how macrophages — specialized cells that act as a front-line defense system for our immune systems — alter the pancreatic cancer tumor microenvironment which plays a key role in how the cancer develops, progresses, and reacts to therapies. “The successful outcome of this research may form the basis for gut bacteria-based therapies or diet-based therapies to improve the survival as well as the quality of life of pancreatic cancer patients,” he said.

“If you’re going to get sick, Philadelphia is a good place to be because we have the best doctors and researchers in the world,” said Bruce. “I have a big mouth. I’ll fight for more and more research money and more and more exposure. Did you know Jack Benny, Joan Crawford, Michael Landon, Patrick Swayze, Steve Jobs, and Alex Trebek all died of pancreatic cancer? My mother always said we need to get a celebrity behind us to tell this story. I don’t plan to quit telling all the stories I have anytime soon.”

Notes From the Field: Seeing Research in Action

More than 1,000 supporters gathered in Fairmont Park for PanCAN PurpleStride Philadelphia 2023 to support the Pancreatic Cancer Action Network (PanCAN). Wistar’s Dr. Rahul Shinde is a PanCAN research grant recipient, and our lab was honored to attend the event and represent the scientific community. People of all ages wore purple to show support with many teams commemorating loved ones lost. I, too, walked in memory of a good friend and uncle who both lost their battles with pancreatic cancer. 

The atmosphere was emotional and inspiring as we heard from a 19-year survivor who described his journey through treatment and recovery. The 5-year survival rate has increased from 10% to 12% in the last few years due in part to PanCAN research and funding. It is their goal to reach a 20% survival rate by 2030.

PanCAN PurpleStride Philadelphia raised over $600,000 with 60 similar events held nationwide. The funds support services for patients and their families, along with research grants to improve early detection and treatment of pancreatic cancer. The Shinde Lab raised more than $1,000 thanks to the support of family and friends. 

Walking among this Philadelphia community of supporters reminds us all of our responsibility to make our research count. PanCAN PurpleStride Philadelphia was a realization of how meaningful our work is. There is heartbreak surrounding pancreatic cancer, but also considerable hope in scientific advancement. 

Notes From the Field Series is written by a member of Wistar’s scientific community and reflects on life, both in and out of a busy biomedical research lab. SK Reiser is a graduate student in the lab of Dr. Rahul Shinde.

Wistar Scientists Find Gut Microbe Byproduct Drives Antitumor Immunity

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.

Rahul Shinde, D.V.M, Ph.D., Receives Pancreatic Cancer Action Network Career Development Award

The Pancreatic Cancer Action Network announced that Rahul S. Shinde, D.V.M., Ph.D., Assistant Professor in the Immunology, Microenvironment & Metastasis Program of Wistar’s Ellen and Ronald Caplan Cancer Center, was bestowed the Pancreatic Cancer Action Network Career Development Award.

Shinde was the Institute’s first Caspar Wistar fellow and was promoted to assistant professor at the start of 2022. He describes his experience as a researcher as “wonderful” and “one in which I have developed personally and professionally” – crediting the collaborative atmosphere and scientific environment at Wistar as excellent support in helping to garner his lab funding. Currently, Shinde is working on characterizing the gut microbiome and host metabolism in the context of immune responses to cancer.

“Growing as a researcher at Wistar is an amazing feeling filled with learning, discovering, and sharing science,” he says, adding that receiving this award at this stage in his research career is an honor. “The PanCAN Career Development Award is a gratifying experience that reassures me that I’m conducting impactful research in my laboratory.”

The $250,000 in grant funding will help propel forward his scientific focus on characterizing how gut microbe-derived metabolites impact immune cell function and support foundational research into a potential supplementary therapy for pancreatic cancer. Shinde elaborates, “The successful outcome of this research may form the basis for gut bacteria-based therapies or diet-based therapies to improve the survival as well as the quality of life of pancreatic cancer patients.”

Research supported by the 2022 Pancreatic Cancer Action Network Career Development Award, Grant Number “22-20-SHIN.”

The Wistar Institute Is Pleased to Announce the Promotion of Dr. Rahul Shinde to Assistant Professor, and the Promotions of Drs. Mohamed Abdel-Mohsen and Alessandro Gardini to Associate Professor

Wistar is honored these talented and accomplished scientists commit each day in their lab to bringing new and creative insights to cancer, immunology, and infectious disease research. Their original research makes them leaders in their fields and goes beyond scholarly achievement, to their belief in collaboration, and the creation of scientific symposia, and educational programs that expand their respective scientific fields. All promotions were effective as of January 1, 2022.

Congratulations to Dr. Rahul Shinde—Promoted to Assistant Professor

Dr. Shinde joined Wistar in June of 2019 as our first Caspar Wistar Fellow and was programmatically appointed with the Immunology Microenvironment and Metastasis Program. In his relatively short time at the Institute, Shinde established a productive laboratory, initiated numerous collaborations both in and out of Wistar, received independent NIH funding, and developed an innovative research program on the impact of the immune microenvironment in pancreatic cancer, one of the deadliest malignancies in humans. His promotion is a tangible recognition of this track record of academic excellence and a testament to the Caspar Wistar Fellow program as an innovative and successful mechanism to help foster the transition to research independence of meritorious early career investigators.

Congratulations to Dr. Mohamed Abdel-Mohsen—Promoted to Associate Professor

Dr. Abdel-Mohsen was recruited to Wistar in 2017 as a member of Vaccine and Immunotherapy Center. As a junior faculty at the Institute, Abdel-Mohsen quickly established himself as an undisputed research leader in multiple fields of investigation, with innovative and groundbreaking contributions in various aspects of HIV biology and therapy, mechanisms of immune recognition and glycomics. In his short time at Wistar, he was recognized with an impressive number of scholarly achievements, including publications in top-tier scientific literature, large extramural funding and speaking engagements at national and international venues.

Dr. Abdel-Mohsen’s energy, collaborative spirit, and engaging personality, all about the science, have made him a go-to person at our Institute, and a premiere colleague and collaborator in the broader Wistar-Penn campus.

Congratulations to Dr. Alessandro Gardini—Promoted to Associate Professor

Dr. Gardini joined the Institute in 2015, establishing a successful, internationally recognized and highly collaborative scientific program. He is a vital contributor of the Gene Expression and Regulation Program in our Cancer Center and has made seminal contributions to our understanding of novel transcriptional networks exploited in tumor development and progression. In addition to his scientific and scholarly achievements, published in top journals, Dr. Gardini has been a great ambassador of Wistar, launching an exciting Ph.D. exchange program with the University of Bologna, establishing productive research collaborations with our colleagues at the Helen F. Graham Cancer Center at Christiana Care Health and organizing a number of scientific and educational venues, including the GER Mini Symposium in 2017.

Expanding the Caspar Wistar Fellows Program

The Caspar Wistar Fellowship is a model for recruiting the best and brightest junior scientists to Wistar where they can build scientific networks and advance their unique independent research programs.

Two years ago philanthropists Doug and Peggy Briggs established the Caspar Wistar Fellowship to attract the most talented junior scientists from across the nation and beyond, and jumpstart their scientific careers. Put at the center of a collaborative nexus of bold and distinguished scientists working in cancer and infectious disease research at Wistar, What can they achieve?

“If we can find the best and brightest junior scientists, I believe we can move their careers along much faster,” said Doug. “They have the potential, and we are giving them a leg up and hopefully more responsibility than even they think they are ready for.”

These supremely driven and curious scientists have a lot on their shoulders, but have the focus, education and courage to become our next generation of scientific leaders.

Dr. Daniel Claiborne, Wistar’s newest Caspar Wistar Fellow, joins the Fellowship from the Ragon Institute of MGH, MIT and Harvard where he is trying to better understand T cells and CAR T cells for the treatment of HIV. CAR T cells, called chimeric antigen receptor T cells, are patient-derived T cells that have been engineered to target and destroy a specific antigen on the surface of a cancer cell. They are considered “super charged” immune cells that act like a living drug, latching onto a tumor cell to terminate it. CAR T cells have been developed as an immunotherapy for cancer, but Dr. Claiborne wants to explore their potential against HIV.

“This is a huge opportunity to start my own lab so there is some trepidation, but it’s what I’ve been working towards for 13 years, so I’m also very motivated as well,” says Dr. Claiborne. “The recent publications I worked on were not the end, but the beginning in our effort to understand the hurdles in repurposing CAR T cells for HIV. We learned a lot about what these cells can and cannot do. The big question in the field is, ‘Why do CAR Ts stop working?’ It’s an open-ended question and a ton of research has already been done.”

Dr. Claiborne brings an entirely different perspective to CAR T research that will enhance our basic understanding of CAR T cells and help inform their use in oncology and immunotherapy.

“The thing we do differently is use a humanized mouse model that carries a functional human immune system,” said Dr. Claiborne. “This is a malleable small animal model with actual human cells and T cells so we can learn more about what makes our CAR T therapies fail. And that’s largely translatable to more than just HIV infection. It informs basic T cell biology and illuminates what makes T cells do their job or not in many chronic disease states. The ability to do that in a small animal model with a human immune system is powerful and one step closer to the question we all think is important: What causes T cells to lose their function.”

Dr. Ami Patel became Wistar’s second Caspar Wistar Fellow in 2020 and has lived a pretty incredible year with lots of big changes. Since the start of the pandemic, Dr. Patel has been a key leader in the SARS-CoV-2 vaccine and immunotherapy efforts at the Vaccine & Immunotherapy Center.

“In September, I became a Caspar Wistar Fellow and then a week later, I went on maternity leave,” said Dr. Patel. “I truly appreciate this opportunity and it’s exciting to pursue my own independent research. I have multiple new experiments in which to design and develop new ideas. And I’m at the early stages building my lab and getting it up and running.”

Dr. Patel was recruited to the program after shining in the lab of Wistar’s Dr. David Weiner, first as a postdoctoral fellow and associate staff scientist. She was appointed as research assistant professor in 2019.

“As a Caspar Wistar Fellow, my new independent research program is focused on understanding the cellular and immune mechanisms associated with vaccine and immunotherapy delivery and using this information to improve the next generation of vaccines against emerging pathogens that could be tomorrow’s next major outbreaks. This is a great opportunity to explore new strategies,” she says.

As she is establishing her research program, Dr. Patel is hiring her own team to manage projects that run the gamut of emerging pathogens.

“Now is the time to put my new ideas to the test and drill down on key independent experiments that will lay the foundation for my research,” Dr. Patel added.

For Dr. Rahul Shinde, Wistar’s inaugural Caspar Wistar Fellow, this stage of independence has brought a myriad of research collaborations. His work focuses on pancreatic cancer and how cancer hijacks immune cells called macrophages, which normally stimulate the immune system and destroy cancer and pathogen invaders. Dr. Shinde is trying to elucidate when and how macrophages shift their function from fighting cancer to doing cancer cells’ bidding in the tumor microenvironment. He is also interested in the gut microbiome and its connection with modulating tumor progression.

“It has been great at Wistar, and such a positive feeling setting up my lab and working to publish,” said Dr. Shinde. “I feel lucky to collaborate with Wistar principal investigators across research fields including autoimmune diseases such as lupus. I’m also exploring pancreatic cancer’s tumor microenvironment that fosters cancer growth and therapy resistance. I’ve been part of several projects making interesting observations.”

Doug Briggs believes giving strong, sharp-minded scientists a platform to launch their careers is most important.

“Bringing these early-career, star scientists along faster in their careers is helping push the biomedical research dial forward. There are big up sides — for us all — with more and faster success in science,” says Doug.

“For Doug and Peggy Briggs to stand up and create this opportunity is very motivating, especially for scientists who do high-risk and out-of-the-box research,” said Dr. Claiborne. “It’s a huge deal. Pursue your ideas and see where they take you.”

The Caspar Wistar Fellowship will continue to boost the potential in early-career scientists it brings to Wistar. With each new Fellow who calls Wistar home, Doug and Peggy’s straightforward belief becomes a more powerful engine for expanding research and pushing the Institute to succeed.

Stay tuned for the fourth Caspar Wistar Fellow to be recruited very soon!

Wistar Appoints Dr. Rahul Shinde as Inaugural Caspar Wistar Fellow

PHILADELPHIA — (July, 2, 2019) — The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease and vaccine research, announces the appointment of Rahul Shinde, D.V.M., Ph.D., as the first Caspar Wistar Fellow.

Shinde’s research focuses on the role of specialized cells that act as a front-line defense system for our immune systems, called macrophages. He investigates how these cells alter the specialized milieu that surrounds a tumor, known as the the tumor microenvironment (TME), which is a key determinant of whether cancer is able to develop, progress and resist therapies.

The Caspar Wistar Fellows Program is a brand-new program and the only one of its kind in Philadelphia that fast-tracks the most promising, early-career scientists to pursue creative, out-of-the box biomedical research for the benefit of humanity. Shinde is the first to be selected into the Program, which cultivates accomplished, intellectually driven postdoctoral scientists from across the nation and beyond and provides Fellows both mentorship and freedom to pursue a strong, independent research program in their field.

Shinde’s laboratory at Wistar will study how alterations in the metabolism of macrophages contribute to their function in cancer progression. He is also interested in the gut microbiome and its connection in modulating the TME and tumor progression. Shinde aims to characterize the key factors that shift the balance between healthy and disease-modulating microbiome and identify new targets for therapies.

“Wistar is a leading research institute with a history of scientific excellence and a far-reaching vision of integrating basic, translational and disease-relevant cancer research for therapeutic benefits. I am thrilled to join the Institute through the Caspar Wistar Fellows Program and integrate my research into the Cancer Center’s innovative programs,” said Shinde. “I believe the state-of-the-art research facilities and the collaborative atmosphere at the Institute will provide excellent support, and I look forward to expanding my ongoing work and contributing to Wistar’s scientific mission.”

Shinde joins Wistar from Princess Margaret Cancer Center, Toronto, ON, Canada, where he was a postdoctoral fellow in the Tumor Immunotherapy Program. Shinde received a D.V.M. from Nagpur Veterinary College, Nagpur, India, and a Ph.D. in biomedical sciences from Augusta University, Augusta, GA.

“This new program was launched with the support of two remarkable donors, Doug and Peggy Briggs, to help recruit outstanding early-career scientists. I am pleased to name Rahul our first Caspar Wistar Fellow as he has distinguished himself with his outstanding postdoctoral work in tumor immunology and embodies the qualities we envisioned for this new position,” said Dario C. Altieri, M.D., president and CEO, director of the Cancer Center, and the Robert and Penny Fox Distinguished Professor at Wistar. “His research will further expand our program on myeloid cell biology and tumor immunology, and he brings a complementary body of knowledge through the critical understanding of the gut microbiome. I believe he will find the ideal support and freedom through this new program at Wistar to grow his scientific career and make important contributions to science.”

The Briggs have been Wistar supporters for more than a decade, and Mr. Briggs has served as a member of Wistar’s Board of Trustees for nine years. The Briggs are highly invested in the work of Wistar scientists and were interested in building a program that provided exceptional, early-career scientists with the autonomy and resources to take an accelerated path toward independence as principal investigators.

“We wanted to create something totally new and game-changing at Wistar by finding the best scientific talent and giving them all the tools and freedom they need to reach their potential — possibly more than they think they’re ready for — to attain that next level and succeed,” said Doug Briggs.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer, immunology, infectious diseases 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.