Author: The Wistar Institute

Sarah Welsh and Joseph Zundell Share the 2020 Monica H. M. Shander Memorial Fellowship Award

Written by The Wistar Institute on November 24, 2020. Posted in Featured News.

Predoctoral trainees Sarah Welsh and Joseph Zundell are the recipients of the annual Monica H. M. Shander Memorial Fellowship Award for outstanding predoctoral research.

This year, the Committee has voted unanimously to split the award between both candidates in recognition of their ability and accomplishments.

Welsh, a member of the Gardini lab, studies basic mechanisms of RNA transcription that regulate how our genes are expressed. She focuses on a protein complex called Integrator and her work could reveal new targets for cancer therapy.

Working in the Zhang lab, Zundell is researching new combination therapies for a type of ovarian cancer with mutations in the ARID1A gene, a disease for which treatment options are currently limited.

Wistar’s Graduate Student Pratik Bhojnagarwala Awarded the Abraham Schlussel Women’s Health Fellowship Award for Ovarian Cancer Research

Written by The Wistar Institute on November 23, 2020. Posted in Featured News.

Pratik Bhojnagarwala is a third-year graduate student in the Cancer Biology Program jointly administered by Wistar and the University of the Sciences. Currently, he’s carrying out thesis work in the Wistar lab of Dr. David Weiner, focusing on designing novel DNA-encoded immunotherapies against cancer. These include monoclonal antibodies and bi-specific antibodies as well as therapeutic cancer vaccines.

Women’s health issues are close to Pratik’s heart as his family has a history of breast and uterine cancers. He believes synthetic DNA is a powerful platform and is excited to continue learning and applying it to advance immunotherapies for ovarian cancer.

“I have designed and developed various monoclonal and bi-specific antibodies that target different tumor antigens expressed on advanced brain cancers and ovarian cancers,” said Bhojnagarwala. “I’m also developing vaccines that target specific mutations that are expressed only on tumors, which would advance development of highly personalized therapy for cancer patients.”

Pratik’s long-term goals are to become part of a team involved in bringing novel cancer immunotherapies through clinical trials and eventually to patients.

Wistar Virtual Champion Run for Research 2020

Written by The Wistar Institute on November 17, 2020. Posted in Featured News.

From the many corners of Philadelphia and its surrounding neighborhoods, Wistar colleagues united to run, walk and raise funds supporting our pre- and postdoctoral trainees. We had an amazing turn out, we all got our blood pumping on this brisk fall weekend, and we surpassed—by far—our goal of raising $3,500.

Thank you to everyone that shared selfies against their sun-infused city backdrops! We had some standout images. Congratulations to the Murphy lab that once again won for most money raised by a Wistar lab!

And a big thanks to the generous support of Cigna, who has matched our many fundraisers and added a generous bump to the grand total. Our first virtual Run for Research could not have been done without you all. See you next year on whatever path you choose to run!

Wistar Creates a New Synthetic DNA Vaccine Against Powassan Virus

Written by The Wistar Institute on October 29, 2020. Posted in Press Releases.

PHILADELPHIA — (Oct. 29, 2020) — Scientists at The Wistar Institute have designed and tested the first-of-its-kind synthetic DNA vaccine against Powassan virus (POWV), targeting portions of the virus envelope protein. A rapidly reemerging tick-borne disease, POWV has been reported to be fatal in 10% of infected people with detrimental neurological consequences including encephalitis and meningitis. This new POWV vaccine candidate, described in a paper published today in PLOS Neglected Infectious Diseases, is one of many emerging infectious disease DNA vaccine discoveries being advanced by the Vaccine and Immunotherapy Center at The Wistar Institute.

Unlike the widely recognized Lyme disease, POWV causes a little known, potentially deadly infectious disease that is transmitted through tick bites during fall and spring seasons. POWV is an RNA virus belonging to the flavivirus family, the same as Zika virus, but passed to people by ticks instead of mosquitoes.

Transmission can occur rapidly and symptoms including flu-like fever, body aches, skin rash, and headaches can present anytime during the 1-4 week incubation period. Although still considered relatively rare, in recent years the number of reported cases of people sick from Powassan virus has been increasing in North America, including infecting former U.S. Senator Kay Hagan who contracted Powassan virus and died from the disease. There are no vaccines or therapies available to treat or prevent this emerging infection.

Kar Muthumani, Ph.D., former associate professor and director of the Laboratory of Emerging Infectious Diseases at The Wistar Institute,* and senior author on the study, collaborated with the laboratory of David B. Weiner, Ph.D., executive vice president and director of Wistar’s Vaccine and Immunotherapy Center, to design and test this synthetic DNA vaccine.

The effectiveness of this vaccine was evaluated in preclinical studies that showed a single immunization elicited broad T and B cell immune responses in mice similar to those induced naturally in POWV-infected individuals, and that vaccine-induced immunity provided protection in a POWV challenge animal model.

“The significant protection in mice demonstrated by our vaccine is highly encouraging and strongly supports the importance of this vaccine approach for further study,” said Muthumani.

Residents of and visitors in POWV-endemic areas are considered at risk of infection, especially during outdoor work and recreational activities. In the U.S., cases of POWV disease have been reported in Northeastern states and the Great Lakes region.

“Given the risk of serious complications from POWV and the 300% increase in incidence of POWV infection over the past 16 years, we will continue efforts to advance this urgently needed emerging infectious disease vaccine candidate towards the clinic,” said Weiner.

Co-authors: Hyeree Choi1, Michelle Ho1, Sagar B. Kudchodkar1, Emma L. Reuschel1, Kenneth Ugen5, Erin Reynolds2, Pablo Tebas3, J.Joseph Kim4, Mohamed Abdel-Mohsen1, Saravanan Thangamani2, David B. Weiner1, Kar Muthumani1
1Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA; 2Department of Microbiology and Immunology, SUNY Center for Environmental Health and Medicine, SUNY Upstate Medical University, Syracuse NY 13210. 3Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 4Inovio Pharmaceuticals, Plymouth Meeting, PA., 5University of South Florida, Tampa, FL.

*Current address: K. Muthumani, CSO, GeneOne Life Sciences, Inc., Blue Bell, PA

Work supported by: INOVIO Pharmaceuticals, Inc.

Publication information: A novel synthetic DNA vaccine elicits protective immune responses against
Powassan virus, PLOS Neglected Tropical Diseases (2020). Advanced 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 collaborations. wistar.org.

National Institutes of Health Funding Powers Wistar Science in 2020

Written by The Wistar Institute on October 23, 2020. Posted in Featured News.

Approaching the end of the year, Wistar takes stock of its federal funding performance.

During the 2020 fiscal year of the National Institutes of Health (NIH) — the U.S. government agency that supports biomedical research, it funded Wistar research by granting more than $43M in existing and newly awarded grants.

“Our ability to attract and maintain federal funding is vital for the success of our enterprise and speaks volumes to the quality of the science being pursued at Wistar,” said Dario C. Altieri, M.D., president and CEO, director of the Institute’s Cancer Center and the Robert & Penny Fox Distinguished Professor. “NIH grants fuel some of our largest and most ambitious research projects and our collaborative efforts and support our Cancer Center, a powerhouse of discoveries and advanced technologies in the region.”

The NIH is made up of 27 Institutes and Centers, each with a specific research focus on particular diseases or body systems, working together to support the nation’s research efforts. The vast majority of Wistar’s active grants are administered by the National Cancer Institute (NCI), reflecting Wistar’s vast commitment to cancer research. The second largest pool of grants comes from the National Institute of Allergy and Infectious Diseases, which supports basic and applied research on infectious, immunologic and allergic diseases, powering Wistar investigations into HIV, Epstein-Barr Virus, antimicrobial resistant bacteria, and tuberculosis.

Highlights from newly awarded grants include:

Two large grants over four and five years, respectively, to Mohamed Abdel-Mohsen, Ph.D., assistant professor in The Wistar Institute Vaccine & Immunotherapy Center, for his glycoimmunology research in HIV. Glycoimmunology is an emerging field focused on the role of sugar molecules present at the surface of our cells, also referred to as glycans or carbohydrates, in mediating immune responses.

The new funding will support Abdel-Mohsen’s work investigating the role of altered host sugar repertoire, or glycome, in gut and brain inflammation and cognitive disorders in HIV. This research aims to discover new mechanisms that could be targeted to prevent or treat chronic inflammation that persists in individuals living with HIV despite antiretroviral therapy.

Applying a similar research paradigm, Abdel-Mohsen obtained additional funding to expand his research to COVID-19. He seeks to understand the integrity of the intestinal barrier in inflammation and COVID-19 pathogenesis. SARS-CoV-2 infection alters the structure of the gut wall making it more permeable to intestinal microbes that can then enter and circulate in the blood. This may lead to a loss of anti-inflammatory circulating carbohydrate molecules in the body, which results in inflammation and worse disease outcomes. This research will lay the groundwork for developing novel biomarkers for disease risk and therapeutic interventions for the COVID-19-induced cytokine storm to prevent severe outcomes and death.

A five-year grant to Qing Chen, M.D., Ph.D., assistant professor in The Wistar Institute Cancer Center, for her studies on brain metastasis, which causes an increasingly heavy clinical burden due to its rising incidence and the limited efficacy of existing therapies. Chen is investigating the interaction between cancer cells and the surrounding brain cells to identify key mechanisms that could be targeted to disrupt this interaction and the cancer’s ability to grow in the brain, and eventually provide more effective therapies for cancer patients.

A five-year grant awarded to Maureen Murphy, Ph.D., Ira Brind Professor and program leader in The Wistar Institute Cancer Center, to further her studies on the p53 protein, a master regulator of numerous functions in the cell and frequently mutated in cancer. In particular, the Murphy lab is interested in the effects of specific genetic variants of p53 on the tumor-promoting ability of the mutant p53 protein. Murphy and her team investigate how these genetic variants affect the cancer risk in different populations, and this research has important implications for informing personalized medicine approaches.

A five-year grant to Rugang Zhang, Ph.D., professor and deputy director of The Wistar Institute Cancer Center, that enables the Zhang lab to study the mechanisms that allow a small number of “dormant” tumor cells to persist in the body after therapy. These cells can awaken from dormancy and start proliferating to give rise to metastases even years after the onset of the primary tumor. Elucidating the underlying mechanisms of tumor dormancy is crucial to achieve cancer eradication.

Two NIH Pathway to Independence Awards bestowed to staff scientists Thibaut Barnoud and Sergey Karakashev, both working in Wistar Institute Cancer Center labs. This prestigious and highly sought-after award supports outstanding postdoctoral researchers in their transition from mentored training to and independent faculty position and boosts the awardees’ competitiveness in the job market

The information on dollar amounts disclosed in this blog is publicly available and has been obtained through the NIH Research Portfolio Online Reporting Tools (RePORT).

Advancement of Anticancer Compounds for B Cell Cancer Therapy Targeting a Cellular Stress Response Mechanism

Written by The Wistar Institute on October 13, 2020. Posted in Press Releases.

PHILADELPHIA — (Oct. 13, 2020) — Researchers at The Wistar Institute and collaborators from the University of Notre Dame are developing anticancer compounds targeting a pathway of the endoplasmic reticulum (ER) stress response implicated in the development of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and lymphoma. The study was published online today in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research.

The ER is an important organelle in our cells that oversees the quality control of protein folding under normal conditions and responds to the accumulation of misfolded proteins found under stressful conditions by activating specific mechanisms and signaling pathways such as the IRE-1/XBP-1 pathway that triggers a cascade of events that brings cells back to normal physiological conditions.

The laboratory of Chih-Chi Andrew Hu, Ph.D., professor in the Immunology, Microenvironment & Metastasis Program at Wistar, and collaborators show that targeting the ER stress signaling response is an effective strategy against various B cell cancers that rely upon ER stress signaling response to survive under stressful conditions.

The Wistar Institute and Notre Dame teams are working together to advance a new class of compounds to inhibit IRE-1 protein and block the function of the IRE-1/XBP-1 pathway, which promotes survival of malignant B cells such as MM and CLL cells. The IRE-1 inhibitors being developed by Hu and collaborators have shown promising activity in several preclinical cancer models, compared to other commercially available IRE-1 inhibitors having variable and inconsistent ability to selectively target ER stress signaling in vitro and in vivo.

“We carefully compared many published inhibitors of the IRE-1/XBP-1 pathway with our own inhibitors, showing that our compounds are the most reliable small molecule inhibitors for targeting this pathway in malignant B cells and that many of the other published inhibitors we tested have subpar activity or adverse off-target effects,” said Hu.

The team measured the ability of various inhibitors to block the RNase activity of IRE-1 in test tubes and within the cells. The best-performing molecules were further evaluated for their cytotoxicity against MM, CLL and mantle cell lymphoma, both as single agents and in combination with PI3K/AKT pathway inhibitors that are used as targeted therapy for these malignancies.

Two inhibitors developed by the team, B-I09 and D-F07, showed the highest and longest-lasting inhibitory activity at lower concentrations.

To improve the tumor specificity of these compounds, Hu and colleagues exploited a feature of tumor cells. Since tumor cells typically produce higher hydrogen peroxide (H2O2) levels than normal cells, researchers designed, synthesized and tested novel inhibitors modified with boronate cages, which require high levels of H2O2 to subsequently turn on their inhibitory activity towards IRE-1.

E-F02, a modified prodrug form of B-I09, could be optimally activated by H2O2 to inhibit IRE-1 in malignant B cells. Furthermore, its killing activity was further enhanced in combination with a compound that induces the production of H2O2 in the cells. “E-F02’s inhibitory activity can be controlled spatiotemporally with specificity against cancer cells in vitro,” said co-corresponding author Chih-Hang Anthony Tang, M.D., Ph.D., a staff scientist in the Hu lab. “Next step is to further test it in vivo in our cancer mouse models.”

“We are interested in collaborating with a biotech partner to complete preclinical testing of our lead candidates in order to pursue clinical development of our IRE-1/XBP-1s inhibitors to target human CLL and many other cancers including solid tumors to one day deliver a new highly specific and effective cancer therapy.”

Co-authors: Andong Shao, Qin Xu, Walker T. Spalek from Wistar; Christopher F. Cain, Chang Won Kang and Juan R. Del Valle (also a co-corresponding author) from the Department of Chemistry & Biochemistry, University of Notre Dame, IN.

Work supported by: National Institutes of Health (NIH) grants R01 CA163910 and R01 CA190860.

Publication information: Development of Tumor-targeting IRE-1 Inhibitors for B Cell Cancer Therapy, Molecular Cancer Therapeutics (2020). Online publication.

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The Wistar Institute is an international leader in biomedical research with special expertise in 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’s Business Development team is dedicated to accelerating the translation of Wistar discoveries into innovative medicines and healthcare solutions through licensing, start-ups and creative collaborations. wistar.org.

The Wistar Institute Announces the Appointment of Scott Cooper, Ph.D., Richard G. Phillips, Jr., and Steven V. Abramson to Its Board of Trustees

Written by The Wistar Institute on October 13, 2020. Posted in Press Releases.

PHILADELPHIA — (Oct. 13, 2020) — The Wistar Institute is pleased to welcome Scott Cooper, Ph.D., Richard G. Phillips Jr., Esq., and Steven V. Abramson, to its Board of Trustees. The new trustees bring diverse expertise and perspectives to the mission of the Institute.

An international museum professional and heritage preservation expert, Scott Cooper, Ph.D., is the president and CEO of the Academy of Natural Sciences of Drexel University. He has dedicated his career to protecting, promoting and transforming cultural sites and institutions around the world. Cooper 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.

Before joining the Academy, he was vice president of collections, knowledge and engagement at the Royal British Columbia Museum in Victoria, Canada; director of museums at the Qatar Foundation in Doha, Qatar; and CEO of the Fulham Palace Trust in London, U.K.

Cooper studied engineering at the University of Manchester and architectural conservation at Edinburgh College of Art. He was awarded a UNESCO scholarship to study stone conservation in Venice and subsequently returned to Edinburgh to complete his doctoral research on Scottish history.

Richard G. Phillips, Jr., Esq., is a visiting fellow at Yale Divinity School. He is also the co-founder of Keepers of the Commons, an initiative that places human dignity at the center of private enterprise and entrepreneurship and creates new opportunities for the development of overlooked nonprofit community leaders by expanding access to well-established policy and events.

Previously, he successfully managed his family’s business, Pilot Freight Services, leading it through a restructuring that modernized the company and significantly increased its revenues. Phillips also served as a counsel to senators on the U.S. Senate Committee on The Judiciary and as a trial attorney in the Department of Justice.

He is heavily involved in the community and received the 2013 Maguire Award for Outstanding Service to the Philadelphia Community among other honors.

Phillips received a bachelor’s degree in history from Yale University, a master’s degree in international relations from Cambridge University and a J.D. from Georgetown University.

Steven V. Abramson is president and CEO of Universal Display Corporation and has been a member of its Board of Directors since 1996. He has spent most of his career supporting the creation and growth of new technologies such as OLEDs, digital cellular radio and fostering the development of sustainable environmental technologies.

He also serves on the boards of a number of charitable and educational organizations.

Abramson received a bachelor’s degree in international relations from Bucknell University, a master’s degree in international relations and philosophy of science from Ohio State University and a J.D. from Temple University.

“We are absolutely thrilled to welcome Scott, Richard and Steven to the leadership of the Wistar community. All three are amazing and transformative leaders not just in their immediate areas of interest but, more broadly, in a variety of disparate disciplines and venues. What they bring to the table is decades-long success, a culture of excellence and a vision of innovation that are perfect matches to the goals and aspirations of The Wistar Institute of the present and future. I truly look forward to closely working with these inspirational leaders to advance the mission of the Institute in global health and bring about the kind of scientific breakthroughs that change society and improve the lives of millions,” said Dario C. Altieri, M.D., Wistar president and CEO.

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A Life at the Intersection of Music, Biotechnology and Business

Written by The Wistar Institute on October 8, 2020. Posted in Featured News.

A conversation with Anne Schoemaker about her vision to sponsor The Wistar-Schoemaker International Postdoctoral Fellowship, a partnership launched in 2019 by Wistar and Leiden University Medical Center (LUMC) in the Netherlands to bring LUMC graduates to Wistar for for postdoctoral training.

As a trained pianist, can you explain why you feel so passionately about biomedical research training and education?

I am a Juilliard-trained pianist, and music remains an integral part of my life, but I never made a living performing. I pivoted away from that life through a graduate degree in business which is what led me, serendipitously, I might add, into the world of biotechnology. As fate would have it, it also led me to my late husband, Hubert J.P. Schoemaker, whom I met during a meeting.

My career in biomedical technology management and licensing explains part of my interest in biomedical research and education. I joined the University of Pennsylvania’s technology transfer group at its inception. I had always enjoyed studying science, had business credentials, and wanted to work in a nonprofit environment, so I found the opportunity to join this nascent effort interesting. But I would not have predicted how much I would enjoy my interactions with scientists and the diversity of the work. That environment also provided something else: a window into the world of research, discovery and innovation and, importantly, an understanding of what is required to fuel the scientific endeavor. I remember thinking that I wished I had paid more attention in high school chemistry class (I was too busy practicing), and I learned that, not unlike mastering a musical instrument, cultivating a research scientist necessitates a program of intellectual discipline and training that begins early and continues over many years.

The other part of my interest derives from my husband’s background as a person who also fell, somewhat serendipitously, into the world of science. As a young student in the Netherlands, academics in general were not of particular interest to him, and only because his father sent him to the U.S. to “improve his English” did he somewhat accidentally find his way to the University of Notre Dame and the study of chemistry. Two years later, he was hooked – on the subject matter and what the scientific tools and repertoire enabled. He later completed a Ph.D. at Massachusetts Institute of Technology in record time, and he often reflected on the value of his education and training at both institutions as fundamental to enabling his seminal contributions to the field of biotechnology.

Why, as a philanthropist, did you choose Wistar to establish a postdoctoral fellowship collaboration with the Leiden University Medical Center?

First of all, I’m a Wistar alumna. Former director Hilary Koprowski hired me in the early 90s to establish the Business Development Department at Wistar, and I was fortunate to work with wonderful colleagues for several years during a very exciting time when the rabies and rotavirus vaccine technologies were commercialized. Importantly, fundamental research on the monoclonal antibody technology that formed the basis of Centocor, the company my husband co-founded, came out of Wistar. If all of these connections weren’t enough, several researchers at LUMC, our inaugural Postdoctoral Fellowship partner, were Centocor collaborators. There are many important and deeply meaningful connections among Wistar, Centocor, my husband, and myself. The choice was, therefore, pretty obvious to me.

What does an international collaboration like this bring to the trainees from Leiden and the Wistar community?

Hubert fiercely believed that collaboration was the surest path to success. In the early days of Centocor, he elevated collaboration very nearly to an art form, replacing a corporate research and development department with many highly cultivated relationships with academic institutions and scientists whose discoveries ultimately became Centocor’s products. These relationships were international: from LUMC to the Max Planck Institute in Germany, the Pasteur Institute in France, and the Imperial College London in the U.K., among others. He celebrated diversity of thinking and culture and believed the energy created by these contrasts provided creative fuel for his company. International collaboration creates a unique form of experiential learning, and this is what trainees can expect from joining us at Wistar as Fellows.

How does the program change due to the global experience of COVID-19?

Sadly for all of us, we have hit a physical pause. The health and safety of the Wistar community and future researchers and staff is paramount, so international travel and relocation is not possible at this time. The program is fully established and ready to be implemented as soon as it is safe to do so, and there is much excitement and anticipation on the part of our Dutch colleagues to operationalize the Fellowship. In the meantime, we continue to engage with our colleagues at LUMC and cultivate additional relationships with interested parties, albeit through digital platforms, as we believe this Fellowship program could be replicable worldwide.

New Mechanism of Cell Survival in Chronic Lymphocytic Leukemia

Written by The Wistar Institute on September 30, 2020. Posted in Press Releases.

PHILADELPHIA — (Sept. 30, 2020) — Researchers at The Wistar Institute unraveled a mechanism employed by chronic lymphocytic leukemia (CLL) cells for their survival. According to the study, published online in Cellular & Molecular Immunology, malignant B cells turn down expression of the STING protein to allow for increased expression of B cell receptor on their surface.

STING is located on the membrane of the endoplasmic reticulum (ER), the cell’s protein manufacturing and packaging factory, and is critical for sensing the presence of DNA in the cytoplasm, which can be associated with cell anomalies or infection by viruses and intracellular bacteria. In response to these conditions, STING promotes production of type I interferons and other pro-inflammatory molecules to enhance immunity. Because of this function, STING activation has been proposed as a strategy for cancer and infectious disease immunotherapy.

The lab of Chih-Chi Andrew Hu, Ph.D., professor in Wistar’s Immunology, Microenvironment & Metastasis Program, studies the role of STING in the context of B cell differentiation and CLL. They previously discovered that STING activation by agonists induce cell death in normal and malignant B cells.

“Malignant CLL cells typically have low STING levels and strong B cell receptor (BCR) signaling that supports their survival,” said Hu, who is senior author on the study. “We explored the role of STING in BCR and B cell differentiation and discovered that reduction in STING expression could contribute to the robust BCR signaling phenotype in CLL cells.”

To investigate STING function in B cells, Hu and colleagues generated two genetic mouse models harboring a permanently activated STING mutant (STING V154M) and lacking STING in B cells (B cell-specific STING knockout), respectively. B cells purified from STING V154M mice had reduced BCR expression and signaling upon stimulation, due to activated STING that could efficiently cause destruction of the BCR through a mechanism called ER-associated degradation (ERAD). As a result, activated STING in B cells suppressed formation of plasma cells and antibody production. Conversely, B cells purified from B cell-specific STING knockout mice showed higher levels of BCR and more robust BCR signaling in response to stimulation, and STING deficiency in B cells promoted formation of plasma cells and antibody production in mice.

“Our studies point to a novel B cell-intrinsic role of STING in regulating BCR signaling and plasma cell differentiation,” said Chih-Hang Anthony Tang, M.D., Ph.D., a staff scientist in the Hu lab and co-corresponding author of the study. “Our findings also suggest that CLL cells may downregulate STING to promote a stronger BCR signaling to support their survival.”

While STING downregulation is also present in other cancer types, it serves the tumor through a different, extrinsic function, reducing the production of type I interferons and preventing activation of antitumor immunity.

Co-authors: Avery C. Lee, Shiun Chang, Qin Xu, Andong Shao, Yun Lo, and Walker T. Spalek from Wistar; Juan R. Del Valle from University of Notre Dame, IN; and Javier A. Pinilla-Ibarz from H. Lee Moffitt Cancer Center & Research Institute.

Work supported by: National Institutes of Health (NIH) grants R01 CA163910 and R01 CA190860.

Publication information: STING regulates BCR signaling in normal and malignant B cells, Cellular & Molecular Immunology (2020). Online publication.

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Women & Science: Developing Immunotherapies for Emerging Pathogens That Threaten Global Health

Written by The Wistar Institute on September 21, 2020. Posted in Featured News.

Wistar’s first Women & Science event of the COVID-19 era took place virtually and, appropriately, featured Dr. Ami Patel, a Wistar scientist that is playing a major role in the work being done at the Institute to develop solutions for the pandemic.

Dr. Ami Patel’s career path unfolded studying different emerging pathogens, each one scarier than the previous: from bird flu to the H1N1 swine flu to Ebola, and now SARS-CoV-2. This led her to work on developing next generation vaccine technologies as an alternative to traditional vaccine strategies that are not always effective against emerging infectious diseases.

Dr. Patel was recently appointed as a Caspar Wistar Fellow and is establishing her independent laboratory to develop next-generation immunotherapies and strategies for infectious diseases and cancer.

She believes the combination of different approaches being explored in this pandemic will be our winning strategy against COVID-19.

“The scientific community has really come together sharing information and resources, informing the public and letting science provide solutions. We are making a lot of advances in a short time,” she said.

Dr. Patel was instrumental in carrying out fundamental studies in animal models to understand what kind of immune responses are stimulated by the vaccine co-developed by Wistar and collaborators and inform what response would be observed in people during the clinical stage.