Author: The Wistar Institute

Bringing Together Cutting Edge Technologies, Daniel Claiborne, Ph.D., Charts a Course for Solving Puzzles About HIV Infection

Written by The Wistar Institute on September 13, 2021. Posted in Featured News.

Mice differ from people in many ways. But over the last decade, scientists have succeeded in engineering mice that are more humanlike in their ability to be infected with HIV, making it possible to study the disease, and develop vaccines and therapies, in these small animals.

As Daniel Claiborne, Ph.D., a Caspar Wistar Fellow who started in August, gets his lab off the ground, these so-called humanized mice, which he worked to optimize during his postdoctoral research, will be central to his research goals. Dan will take advantage of two other technologies that have recently come of age: CAR T-cell therapy, which is used to treat certain blood cancers, and transcriptomics — or the large-scale study of gene expression, to tease apart how T cells function in these mice and, like in people, stop functioning during HIV infection. It was truly a trifecta — “none of these technologies existed, even in isolation, until fairly recently,” Dan said.

Perfect Timing

Dan clearly remembers the thrill of reading the email from The Wistar Institute inviting him for a job interview. “It felt good because I had a shot to talk about what I’m passionate about and to explain to people my vision,” Dan said. As soon as the interview was over, he had no doubt that Wistar was where he wanted to be.

In fact, the timing seemed perfect because, although the humanized mouse model has not been widely embraced, the Institute believes so strongly in its potential, as Dan does, that it is launching a research program around it. Since he has joined, Dan and his new colleagues have wasted no time discussing how they can collaborate together and capitalize on Dan’s deep experience working with the mice during his postdoc at the Ragon Institute of MGH, MIT and Harvard, and his understanding of which aspects of the immune system they recapitulate well and which they don’t. For example, Dan can help another lab take a small molecule they found has interesting properties in cells in a Petri dish and study it in these small animals.

Dan also looks forward to what he can learn and share with just the other new recruits, three assistant professors, who are also joining Wistar this fall. “You always have peers, but to have true peers that are just starting out is kind of amazing,” he said.

Mining the Data

Going into his interview, Dan already knew the Philadelphia area well. As a postdoc, he had been collaborating with James Riley at the University of Pennsylvania, combining his expertise with HIV-susceptible humanized mice and the Riley lab expertise making CAR T cells specifically designed to recognize and kill HIV-infected cells.

This collaboration will continue now that Dan is at Wistar. While the Riley lab is focused on developing CAR T cells as a potential cure for HIV, Dan sets himself apart by making use of these engineered T cells, which he calls an “untapped resource,” to tease apart how they become exhausted and lose their ability to fight off HIV, just like natural T cells do, during infection. Dan plans to use a host of molecular tools to try to prevent CAR T-cell exhaustion and then probe what the precise pathways and gene expression profiles are within these cells that allow them to retain anti-HIV activity. The experimental system is in place, Dan said, and now “we just need to mine it.” What they find could ultimately help his collaborators who are working toward a CAR T-cell HIV cure figure out ways to make the therapy more effective.

For Dan, collaborations are not just really fun but absolutely necessary. “I tend to take on more ambitious and risky projects that take a lot of labs working together. I think biomedical science has evolved into that, where the questions we are asking really involve a lot of expertise that rarely is contained in one lab.” He thinks Wistar is fertile ground for these relationships because the small private institution really embodies the spirit of partnership.

Inspired by Immunology

For Dan, being easily bored has served him well. It made the idea of science, and constantly learning something new, seem very appealing to him as he was growing up. As much as Dan always knew he wanted to be a scientist — and counts himself in the lucky minority for figuring it out early, he recharted his course as an undergraduate at Florida State University. He started off focusing on organic chemistry, but soon decided the lab work was far too dull. Then Dan took an immunology course about halfway through his degree and he was hooked. He promptly started a project in the professor’s lab and never looked back. “I was so fascinated with immunology because it was so clear that we didn’t know anything, but the things that we did know were awesome,” Dan recalled. For the first time, he was motivated to go for his Ph.D., which he got at Emory University, instead of getting a job after college.

While being easily bored turned Dan on to science, being stubborn made him stick with it. Through what he calls the “fourth year grad school slump” and the ups and downs of his postdoc, he refused to quit. “It’s just part of how I’m wired, I keep after it until I get somewhere,” Dan said. “I have been lucky that I have not suffered from a lack of conviction.”

Happy Homemaker

In addition to brainstorming about collaborations with his new colleagues, Dan’s first few weeks at Wistar have involved a lot of ordering lab supplies. Even though he oversaw a small team of scientists during his postdoc, it never really occurred to him that many of the reagents they used for experiments didn’t just come with the lab space. Nevertheless, he is enjoying the experience. “It is like Christmas, you get to go on a shopping spree.”

There is plenty for Dan to set up at in his new home, too. He and his wife moved to the Philadelphia area with their three-year-old son and their infant son, who was born about the same time that Dan started his own lab. He jokes that he will get back to his old hobbies such as lifting weights one day, once he gets a handle on some kind of work-life balance. “It is all good things, just smashed into a really small timescale,” Dan said.

Written by Carina Storrs, Ph.D.

Cheyney University students working in the Wistar Training Lab

Cheyney University Students Kick Off Their Biomedical Research Journey at Wistar

Written by The Wistar Institute on September 13, 2021. Posted in Featured News.

Last February, Wistar welcomed the inaugural group of Cheyney University students enrolled in the biomedical research and training program co-developed in 2020 by the nation’s first biomedical research institute and the nation’s first historically black college and university.

“As a biomedical research instructor and someone who loves science, I firmly believe that the way to teach it effectively is to have the students do science. I am really excited to give these students an authentic research experience at Wistar.”

This statement by Dr. Kristy Shuda McGuire, dean of Biomedical Studies at Wistar, summarizes this initiative, which was recently launched to provide students with hands-on, real-world experience in the lab and introduce them to the many career paths in biomedical research.

To maximize the potential of the Wistar – Cheyney alliance in research and business development and support other Wistar workforce training programs, the Institute has assembled a Workforce Advisory Council including experts from the local biotech arena and academia. The Council helps forge and oversee new connections, match students with internship opportunities, and advertise the programs, expanding Wistar’s presence in the Philadelphia life sciences community.

The strategic collaboration between Wistar and Cheyney will provide career development opportunities, preparing students for future jobs in science while they earn their degrees.

“At Cheyney University, we constantly look for new partnerships that can create more opportunities for our students,” said Dr. Nicole Santerre, assistant professor of biology at Cheyney and one of the instructors of the course. “Wistar seemed like it was a partnership that was meant to be. It was very exciting to work on this project because it was built with our students in mind the whole time.”

The Cheyney students were the first to learn in Wistar’s brand-new teaching and training lab, a 1,500-square-foot education suite featuring open bench space, a tissue culture room and an instruction area equipped with smart TV access.

In this setting, students have taken the Biomedical Research Methods course, which represents the first half of the curriculum, learning cutting-edge techniques under the mentorship of Drs. McGuire and Santerre.

“Our approach to training the students is to let them work independently to learn how to follow a protocol, while we are there to answer questions, give directions and correct any techniques,” said Dr. McGuire.

Whether hard-core science enthusiasts with a future in the lab or aspiring physicians who want to learn more about research, all the students were excited to be part of this program and think it has made a difference for them, each in a unique way.

Abimael Bellinger, a sophomore in biology, has been attracted to science since he was a child. He thought he wanted to go to medical school; but his experience at Wistar is helping him see that research is an area he wants to explore as a career, and he’s now considering taking the M.D./Ph.D. route.

“Undertaking lab work at your college is not the same as actually performing the experiments in a real lab. At Wistar, we had an opportunity to connect what we read in books with how to apply it,” said Abimael. “I also love that we’ve been taught independence: We learned together and worked side by side but each of us did our own experiments — it was a very individualized experience.”

Amber Young is a senior in biology and in the pre-medicine track. She wants to be a psychiatrist and realized that she needs to be in the know on the latest research, so the Wistar course gave her a chance to explore the scientific world.

“Every student should take this course to get one-on-one experience and find out their capabilities in science,” Amber said. “I’ve always been fond of science because I love exploring and there’s always something new to discover,” she added. “I know there’s a world full of opportunities for me in science but I was nervous about working in a lab. I thought I was going to mess something up, start a fire… Until I came to Wistar and the instructors patiently encouraged me, made me feel comfortable and pushed me forward.”

“When I teach students science in the classroom, I try to talk the least amount possible and instead to ask questions to get them talking and engaged,” said Dr. Santerre. “This approach works in the lab as well. When students ask questions, we ask back: What do you think you are supposed to do? What are you trying to achieve? They eventually come up with answers on their own.”

“I had never had lab experience before and was anxious,” added Lauren Ballard-Coleman, also a biology major in the pre-medicine track. “But I realized I shouldn’t be nervous because this course takes an intimate approach and lets everyone move at their own pace. I really appreciate that and I can now breeze through a protocol on my own!”

Lauren wants to be a physician. It’s her drive and passion and what she feels is meant for her. She knows that the experience at Wistar gave her useful knowledge and will help her stand out on her application to go to med school.

Zainab Sulaiman, a junior majoring in biology, will honestly say that she wasn’t cut out to do research in a lab but to instead work with patients. Yet, she welcomed the opportunity to participate in this course because she’s interested in learning more about research and thinks it’s important to enhance her knowledge on how to work in a lab.

“I learned that I could go into research, not just work on the floor with patients,” said Jamila Roper, a senior biology major in the pre-nursing track. “This experience revealed to me that I would be very well suited to work in a lab and that I also have other options besides becoming a nurse.”

Students did not just learn techniques, they explored real research taking place now in the lab of Dr. Maureen Murphy, who studies the impact of some p53 genetic variants on cancer risk in people of African descent. Working with normal cells and cells that contain one of these variants, students were tasked with investigating the differences at the DNA, RNA, protein and cellular levels.

“Wistar also arranged to have guest speakers of African descent talk about their own journey, how they got where they are, some of the hardships students may encounter both academically and socio-economically, and how they can overcome and succeed,” said Dr. Santerre.

“I’m very excited that some of the students will pursue 12-week research internships in Wistar labs this summer,” said Dr. McGuire. “Some will come back to Wistar in the fall, joined by new students, for the Life Science Innovation course, where they will explore key concepts related to intellectual property, regulatory affairs, and commercialization.”

“Some of the students in this inaugural group had been in a lab before and were more confident; some had never been and were not. It’s been amazing to watch them learn and see how much confidence they’ve gained in just a few weeks. At the end of the course, you couldn’t tell who was who,” Dr. Santerre added. “They were all very excited to be at Wistar and can’t wait to take the knowledge they are acquiring onto wherever they go in the future.”

Motivated By the Hard Questions in Cancer Research, Noam Auslander, Ph.D., Forges New Paths in Computational Biology

Written by The Wistar Institute on September 13, 2021. Posted in Featured News.

Many people unwind in front of the television after a long day. But Noam Auslander, Ph.D., who joined The Wistar Institute Cancer Center in June as an assistant professor, often spends the evening glued to the screen of her MacBook Pro laptop instead, looking for new insights into how tumors progress and cause disease.

“Sometimes I enjoy my work so much that it is my hobby,” Noam said. The most exciting moments are when, by using innovative algorithms that she builds, she starts to see patterns emerge from a data set that hint at an answer to one of her questions. The question she’s beginning to explore at Wistar is complicated — why some tumors metastasize while others do not, but Noam thinks enough data may be available, from the growing number of cancer patients getting genetic testing, to tackle it.

Joining the Community

Noam gravitated to Wistar because of its small environment, quite a contrast from the sprawling National Institutes of Health where she did her postdoctoral research. She felt Wistar would be the perfect place to foster opportunities to work with colleagues. “My work is dependent on collaborations,” Noam said. As a computational lab, she relies on data sets, and although many are publicly available, data that her colleagues have collected, both from patient samples and lab experiments, could greatly enhance her studies.

Collaborating with labs that conduct experiments, such as in cell lines and mice, is also critical for Noam to be able to test, and hopefully validate, what her algorithms show her in biological systems that mimic cancer processes. During her postdoc, for example, Noam and colleagues found that certain types of cancers harbor either high number of genetic mutations or aneuploidy, which is an abnormal number of chromosomes, but never both. It was a finding ripe to explore in cells, as a separate research group did, to identify possible new treatment strategies for aneuploidy cancer cells, which are particularly untreatable.

Bringing Together Computers and Biology

Growing up in Israel, Noam got a head start in computers. She was only 12 when she took her first elective course in the subject, like many of her peers. By the time Noam finished high school, she had a strong enough foundation in coding that she focused on computers during her mandatory two-year military service. But the work nearly zapped her passion. “It’s nice when you’re learning something in the beginning, but then you’re just doing the same thing over and over again,” Noam said.

Fortunately, Noam sought the advice of a friend who was getting his M.D.-Ph.D. Although Noam’s father was hoping she would follow that path and become a medical doctor, her friend listened to her interests — which included biology but not working with patients! — and instead suggested she combine computer science and biology. It was a revelation to Noam, and she headed into a dual degree at Tel Aviv University. The first three years were a slog, as computer science and biology were taught separately, unlike at many schools where they are melded into some type of bioinformatics program, and it was hard to see how the two could fit together. But Noam stuck it out and she was rewarded with the joy of finally learning how to apply algorithms to answer biological questions.

During the years at university, and then carrying out her Ph.D. at the University of Maryland and postdoc at NIH, Noam has witnessed a coming of age of the application of algorithms and artificial intelligence (AI) in biomedical research. “In some aspects of cancer research, it is on the verge, like in radiology,” Noam said. For example, AI can now be used clinically to analyze images to detect certain tumor types.

However, in the areas that Noam studies, genomics and omics data in general, she explained that AI has a lot of room for improvement, in accumulating sufficient data sets, in determining how to best represent the biological language of DNA, RNA and protein sequences in algorithms, and in making the processes of machine learning models understandable to clinicians who may one day rely on them to make treatment decisions. Noam hopes to help overcome some of these challenges, such as by creating algorithms that rely on more interpretable methods.

As she builds her lab at Wistar, Noam will set her sights on another pillar of Wistar’s research: infectious disease. She plans to use a method she developed during her postdoc to identify bacterial viruses, or bacteriophages, to look for new viruses in tumor cells. She suspects that there are many unidentified viruses out there and some may be present in cancer cells, which could either spur cancer progression or serve as a biomarkers of disease. “The original bacteriophage project was easier, but this is more interesting. It is a stepwise process to get there,” Noam said.

Already at Home

Noam will welcome the first postdoc and technician into her group this fall. They will work at stations in the lab with their own laptops — and the space will soon look like all the labs Noam has worked in over the years.

In her own office, Noam already feels settled in at her desk. The view from her windows is filled with lush trees. But as soon as those trees lose their leaves and it becomes winter, Noam looks forward to embarking on getaways for her second favorite activities after science: skiing and snowboarding. That is, if she can pull herself away from her laptop.

Written by Carina Storrs, Ph.D.

Studying Immunology and Cancer, Nan Zhang, Ph.D., Delves Into Mysteries Of Ovarian Cancer Metastasis

Written by The Wistar Institute on September 13, 2021. Posted in Featured News.

Few biologists can say they saw a type of cells for the first time. Nan Zhang, Ph.D., who started at The Wistar Institute in September as an assistant professor, became one of those biologists when, during his postdoctoral research at Washington University in St. Louis, he peered through a microscope into the abdomen of mice and spotted macrophages floating in the cavity. Before that moment, these immune cells had been seen in other compartments in the body, but they were always anchored to tissues.

Nan fondly remembers the day of that discovery, five years ago, and prizes the first video he took of the floating macrophages. “I’m putting this video on my website and trying to put it everywhere. I’m so proud of this, it is really the first of the first,” he said. Along with getting very cool images, Nan’s work shed new light on important functions of these so-called resident peritoneal macrophages. At Wistar, he will use this insight to explore how these cells influence the outcomes of a major disease of the peritoneum, or abdominal cavity: ovarian cancer.

First and Last

It almost felt like a sign that Nan’s first job interview was at Wistar, the place he had his heart set on working. The Institute’s triple focus on cancer, immunology and virology aligned perfectly with Nan’s interests. Of course those kind of stakes only made the interview more stressful, but Nan laid it all on the line. He was shocked when he got an offer, and accepted it without waiting to look at any others.

Nan has trouble naming just one reason — or even three — that he is thrilled to be joining Wistar. He is excited that the small private institution will afford him the time to focus on his own research, without classes to teach, at least for the first several years. At the same time, he can get the feel of a larger research community when he wants it by attending seminars and conferences across the street at the University of Pennsylvania. Last but not least, Nan looks forward to the outstanding facilities at the ready for Wistar scientists, including the special two-photon microscope that will be key for his upcoming studies of peritoneal macrophages in living mice.

Chasing Mysteries

Growing up in China, there were two main influences that fostered in Nan a general interest in science: conversations with his dad, who is a professor of urban design, and children’s magazines about space science and other areas of science. Astronomy was actually Nan’s first real love in science, and he continues to watch videos and listen to podcasts about the topic. He also enjoyed courses in physics and chemistry, and the calculations behind them — basically anything but biology, which in his high school amounted to just a bunch of memorizations.

One day, when Nan was about 16 years old, while waiting on their bikes at a red light, Nan and a friend embarked on a “what if” conversation that awakened in him a fascination with biology and set him on a new path. The pair mused about whether human beings could become immortal by transplanting the memories of one person into a younger person’s body — a science fiction fantasy that Nan noted some people claim they can achieve. It left Nan inspired to ponder ways to improve human health and longevity. When it came time to declare his university major, which in China generally happens at the time of entry, Nan was split between biology and astronomy, but his parents urged him to think about career prospects. He picked biology, reasoning that there will always be jobs for people who study health and disease.

During his Ph.D. research at the University of Oklahoma Health Sciences Center, Nan was struck by another biological mystery, this one more solvable than immortalizing people. As inflammatory cells called neutrophils flood the peritoneal cavity in response to an insult, macrophages — which are immune cells that engulf and destroy invaders — disappeared from the cavity. Nan was so intrigued that he considered switching Ph.D. projects to study this strange phenomenon, which had first been documented decades before, but his advisor cautioned him to stay the course. Instead, Nan read all he could about macrophages in the peritoneum as well as subsets that reside in other tissues and organs, and their different gene expression profiles and characteristics.

By the time he was looking for postdoc positions, Nan had no doubt that he wanted to investigate what peritoneal macrophages were doing and whether they truly had different functions than other subsets of macrophages. What he discovered actually helped solve the puzzle of the macrophage disappearing act. When he injected agents that mimic infection in mice peritoneum, he realized the macrophages clump together, entrapping microbes and clearing them away. Now Nan plans to ask whether the same processes may allow these macrophages to aggregate around ovarian cancer cells, possibly either preventing or promoting metastasis. He will also explore the role of other macrophage subsets in the peritoneum in ovarian cancer progression.

Looking Outward

Nan cannot get his research program at Wistar up and running fast enough. For that reason he is pleased that his lab space is right next to the building entrance, no need to climb stairs or wait for elevators. “If I could teleport to work, I would probably just teleport,” Nan joked.

Near the top of Nan’s to-do list during his first weeks at Wistar is to apply for another big federal grant to fund his research. It will require a lot of writing, which Nan despised during school and his scientific training. It was actually the major reason he doubted his dream of becoming a professor. But the perfect score and enthusiastic feedback he got for his previous grant, which is supporting his transition to an independent scientist, infused him with the confidence that maybe he could make it in academic research.

In the second half of Nan’s postdoc, he made another realization that bodes well for the path ahead: He really enjoys mentoring young scientists and watching them grow. He knows he will be giving them a lot of guidance and cheering along, like his advisors gave him during rough times when experiments did not work. He also looks forward to unleashing the members of his lab to be creative and think crazy thoughts, just as his postdoc mentor encouraged him to do.

As Nan and his wife settle into their new home, he looks forward to nurturing in his five-year-old son the love of science his own father shared with him. Their early discussions together will probably center around Nan’s other science fascination, astronomy. As soon as he can, Nan is going to buy his son, and himself, the telescope he has always wanted.

Written by Carina Storrs, Ph.D.

Bold Science, Global Impact: A Transformational Roadmap for The Wistar Institute

Written by The Wistar Institute on September 10, 2021. Posted in Featured News.

The Wistar Institute Board of Trustees approved the 2021-2026 Strategic Plan that will catalyze the Institute’s scientific excellence, innovation, and growth. The power of science has never been clearer, and Wistar, as a single mission non-profit biomedical research institute, will seize its moment to advance discovery research that delivers new solutions to combatting global health crises.

The five-year Plan is ambitious and clearly charts a course for Wistar to deliver on its commitments to bold and innovative science, to next-generation models of life sciences training and education, and to the creation of transformative global, national and local research collaborations.

“This blueprint reflects our Institute-wide commitment to push forward and deliver purposeful, impactful advances in three core areas that define us: scientific freedom to do the nimblest, technologically advanced science with a transformative impact on society and beyond; commitment to championing equity, diversity, and inclusion in unique education programs for students domestically and globally; and dedication to achieving more growth and success working with like-minded collaborators focused on biomedical research and technology to solve human health challenges,” says Dario Altieri, M.D., Wistar president and CEO, Cancer Center director, and Robert and Penny Fox Distinguished Professor. “There is no better time than now.”

The Institute will expand its NCI-designated Cancer Center and Vaccine & Immunotherapy Center through the recruitment of new and talented scientists having diverse perspectives and technological skillsets. During the next five years, Wistar will be expanding its footprint from 34 to 50 laboratories focused solely on cancer, infectious disease, and translational research to accelerate the development of novel therapeutics, vaccines and diagnostics.

Wistar will enhance its role as education innovator to train and engage diverse students. Our education programs have been recognized as models and will continue to expand and inspire the next generation of scientists, pushing the envelope of learning and access to science beyond geographical borders.

True to its unique and collaborative approach to science, Wistar will expand partnerships to innovate and evolve our high-risk, high-reward scientific research across cancer, infectious disease and translational research disciplines.

Education And Training For A Wistar Workforce Of Future Scientists

Written by The Wistar Institute on September 10, 2021. Posted in Featured News.

Building on educational efforts and a portfolio of education initiatives, Wistar has significantly invested in its mission to train future scientists.

Whether through working with the state of Pennsylvania for the accreditation of a new apprenticeship program in biomedical research, or creating local and international partnerships with colleges, universities, and companies, Wistar is advancing new cutting-edge programs to train nontraditional and underrepresented students for careers in the life sciences.

As an integral part of the Bold Science // Global Impact Strategic Plan, the Institute is looking ahead to strengthen and expand its commitment to education and training over the next five years.

Wistar training programs serve a diverse student population, ranging from high school students experiencing their first biomedical research opportunity, to undergraduate students seeking careers in the biotechnology and biopharmaceutical industries, graduate students pursuing their thesis research, and postdoctoral fellows preparing for independent careers.

Through recently launched collaborations with European universities, Wistar’s reach has expanded beyond national borders. In the fall of 2020, three Ph.D. students from the University of Bologna, Italy, matriculated into the Wistar-Unibo Exchange Program in Cell and Molecular Biology. They will spend a three-year period at Wistar to complete their graduate training in Wistar laboratories.

“From my own training experience, I knew that working in a lab abroad is a very stimulating and mind-expanding experience and it can bring the best out of students” said Dr. Alessandro Gardini, Wistar assistant professor in the Gene Expression & Regulation Program of the Cancer Center and a Unibo alumnus, who worked to make this program a reality.

A second small group of students is preparing to join the Institute and start their training in the fall.

“I applied to the Wistar-Unibo Ph.D. Exchange Program because working in an excellent international research environment is important for my career,” said Simona Lombardi, one of the inaugural students. “I love Wistar’s commitment to the fight against cancer and other diseases, and since this is what I want to do, it is the perfect place for my pre-doctoral training.”

A year before the Unibo collaboration, the Wistar-Schoemaker International Postdoctoral Fellowship was launched in partnership with Leiden University Medical Center (LUMC) in the Netherlands. This postdoctoral training program brings LUMC graduates to Wistar for their postdoctoral training under the mentorship of a Wistar faculty member.

Designed with training in mind, the program also created a connection to establish new scientific collaborations between the two institutions that share several areas of research interest. At the ready to welcome the inaugural trainees, Wistar and LUMC have come together for a virtual seminar series between the scientific leaders and faculty from both institutions to highlight potential collaborative avenues.

“Building more opportunities for international exchange in the training of junior scientists benefits all those involved,” said Dr. Dario Altieri, Wistar president and CEO. “International mobility offers invaluable opportunities for personal and professional development for students and trainees. At the same time, they enrich the host institution with their scientific and cultural background and, when they return to their home countries, they propagate the knowledge they’ve acquired and the scientific approach they have been exposed to. Last but not least, exchange programs create new opportunities for research collaboration.”

As part of the Strategic Plan, Wistar will strengthen its commitment to training programs that enhance equity and inclusion in the life sciences to create a diverse talent pipeline.

Last spring, students from Cheyney University of Pennsylvania kicked off their biomedical research journey at the Institute as part of a new training program co-developed by the nation’s first biomedical research institute and the nation’s first historically black college and university (HBCU). This strategic collaboration between Wistar and Cheyney provides career development opportunities and prepares students for future jobs in science while they earn their degrees.

The first trainees to access Wistar’s brand-new teaching and training lab, Cheyney students learned cutting-edge laboratory techniques through a Biomedical Research Methods course. A second course will introduce them to life science innovation with concepts related to intellectual property, regulatory affairs, and commercialization to show how science extends beyond the lab to solve real-world problems.

The Biomedical Technician Training (BTT) Program, Wistar’s flagship education and training program is also undergoing important changes to meet the growing needs of our students and the life science sector.

For more than 20 years, the BTT Program has opened Wistar’s doors to Community College of Philadelphia (CCP) students for two summers of hands-on training in biomedical research to prepare them for jobs as laboratory technicians and research assistants. To engage a wider student population, the Program has enhanced the curriculum, while condensing the timeline to one summer. To support this work Wistar received a National Science Foundation (NSF) Advanced Technological Education (ATE) project grant appropriately titled, ExCEEd BTT: Expansion, Curriculum Evolution, and Enhancement during BioTechnician Training.

“We realized a shorter BTT Program would fast-track trainees into jobs or the next step of their education,” said Dr. Kristy Shuda McGuire, Wistar dean of Biomedical Studies.

Importantly, ExCEEd BTT will expose every student to both academic and industry settings, including full-time laboratory experiences in one of several collaborating local biotech companies.

Curriculum evolution was an important area of focus. The new project-based, Wistar-branded training curriculum is modeled on Wistar research underway in the laboratory of Dr. Maureen Murphy about the impact of genetic makeup on cancer risk and treatment options.

“We are thrilled to welcome students from additional community colleges in Pennsylvania and even neighboring states,” she continued. “This past summer, our number of trainees was limited to 12 due to COVID-19 restrictions, but starting next summer we are planning to increase the size of the cohort each year.”

One goal of the Bold Science // Global Impact Strategic Plan is to launch a Wistar Center for Education and Training. By bringing all our unique educational programs under a single umbrella and integrating these efforts, we can strengthen our commitment to training the scientists of the future in our region and globally.

Destined for Science, Amelia Escolano, Ph.D., Develops New Vaccination Strategies to Outsmart HIV-1, and Other Highly Mutating Pathogens

Written by The Wistar Institute on September 9, 2021. Posted in Featured News.

Scientists developed COVID-19 vaccines in record time — less than a year after the genome of the virus was sequenced, countries started authorizing use of multiple vaccines. But the virus is rapidly changing, and new variants have been emerging that are more likely to overcome the protective barrier from vaccination.

Amelia Escolano, Ph.D., who became an assistant professor at The Wistar Institute in September, wants to help science regain the advantage. During her postdoctoral studies at The Rockefeller University, she pioneered a new form of vaccination against HIV. She proved that this type of vaccination regimen involving sequential immunization would be necessary to induce broad protection against HIV. At The Wistar Institute, one of her first research goals will be wielding what she learned in her postdoctoral work to develop universal vaccines against HIV-1, other viruses — including cancer-associated-viruses, and tumor neoantigens.

Branching Out

For Amelia, everything clicked about being at Wistar. “It is exactly the kind of place I was looking for,” she said. She thinks the size of the institute is just right for sparking discussion and collaboration. Amelia is already feeling the support of her new colleagues, and excited about all the disciplines she will be exposed to through interactions with scientists at neighboring academic institutions, such as the University of Pennsylvania.

Although her postdoctoral project at The Rockefeller University centered largely around HIV, Amelia looks forward to casting a wide net in her own lab. “The fact that the Cancer Center is here is going to open up new avenues of research and synergies,” Amelia said. She is already brainstorming with several new colleagues at Wistar about how they could collaborate to design vaccination strategies against cancer–associated viruses and tumor neo-antigens.

A Scientist is Born

Amelia cannot think of a time when she did not want to be a scientist. Both of Amelia’s parents were chemists so it would seem to be in her blood.

Amelia’s first hands-on experience happened when she was only about four years old and she received a little microscope as a gift. She dashed outside to collect bugs and puddle water from the backyard of her home in a small village in northern Spain and then sprawled out on the floor to study the specimens using her new equipment. Amelia’s decision to focus on biology was also a no-brainer as soon as she started learning about the cell in school. “I was actually fascinated by the cell and the size of molecules, and how such tiny things could have such interesting functions,” Amelia said.

Amelia had some setbacks in her career and sometimes muses about why she has stuck it out in science. “I must really love it” is the only answer she can provide. “The satisfaction you feel when things finally work makes you forget all the failure the months before,” Amelia said. It is the thrill of knowing that “you had this important question and then your experiment gave an answer and nobody else at the moment knows it,” she explained.

Next Steps

At the heart of the strategy to make a universal HIV-1 vaccine is injecting a series of different versions of a viral component, in this case part of the HIV-1 envelope protein. This strategy is believed to be necessary to induce a broadly protective immune response against HIV-1. Amelia showed during her postdoctoral studies that the first of these injections had to be with a highly engineered envelope protein and that using more natural versions of this component for subsequent injections helped achieve the desired result: broadly neutralizing antibodies that can protect against many different strains of HIV-1. She will continue animal studies at Wistar to optimize sequential immunization approaches.

When Amelia started hearing about COVID-19, she immediately thought that SARS-CoV-2 which causes COVID-19, could be a target for sequential immunization. She suspects this virus will be an easier target than HIV-1 because of the lower mutation rates. She thinks a series of injections with natural versions of spike from a range of newly emerging SARS-CoV-2 strains may lead to broad protection from multiple variants. Amelia sees no limit to the applications of this approach to viruses and bacteria. “The same approach can be translated for all types of pathogens in general that mutate over time,” she said.

Building a Platform

Amelia expected some challenges at the time of recruiting personnel as an early-stage investigator, however, she has been pleasantly surprised. “People are interested in the projects,” Amelia said. “My previous work on vaccine design was well-timed so that I can now join the current research workforce aiming to develop new vaccines”.

As a Finalist in the prestigious Blavatnik Regional Awards for Young Scientists in 2020, Amelia has been more motivated than ever to use her special platform to push for the advancement of women in science and all STEM fields. In addition to trying to support and inspire the many female scientists she has mentored, Amelia speaks out to increase representation of women in different scientific environments. She hopes to continue these efforts taking advantage of her new position at The Wistar Institute.

As she grows her research program, Amelia has no shortage of hobbies to help take her mind off science’s many roadblocks. She loves running and just about all outdoor activities. She also disconnects from work by drawing cartoons of characters that live in her imagination. Amelia has even entertained the idea of illustrating books to promote science to help give the next generation of scientists the excitement she had as a young kid.

Written by, Carina Storrs, Ph.D.

Viruses and Cancer

Written by The Wistar Institute on September 8, 2021. Posted in Featured News.

Viruses impact human health in many ways and can be the underlying agents that cause cancer.

The pandemic has reminded us how pervasive viruses are in human life. We know they can cause infection, making us very sick, but did you know that about 15 percent of all human cancers worldwide may be attributed to viruses?

Drs. Paul Lieberman, professor, and Italo Tempera, associate professor, both in the Gene Expression & Regulation Program of The Wistar Institute Cancer Center, investigate the link between the Epstein-Barr Virus (EBV) and malignant transformation to find ways to treat EBV-related cancers.

EBV is a very common virus. You know it as mononucleosis, and it is spread through saliva, but also through sexual contact, blood transfusions and organ transplants. It mostly infects B cells, a type of white blood cells that produces antibodies. The majority of the world population is infected and carries the virus in a silent state for life. However, in people with compromised immune systems, EBV increases the risk of B-cell lymphomas including Burkitt’s lymphoma and Hodgkin’s lymphoma.

Since it can also infect other types of cells, this virus is not only associated with blood tumors, but also with ten percent of all gastric cancers and most cancers of the nasopharynx, the region behind the nose and above the back of the throat.

How are viruses implicated in cancer?

They are particles made up of DNA or RNA surrounded by a protein coat. With such frugality comes the lack of the necessary machinery to replicate their genome or build proteins, so viruses hijack a host cell and use its machinery to make copies of themselves. In the case of oncogenic or cancer-causing viruses, this process can meddle with the cell’s genes and derail the mechanisms that keep cell proliferation in check, leading to uncontrolled growth.

Oncogenic viruses establish chronic but latent infections that don’t cause obvious symptoms in healthy individuals, because their immune system keeps infection at bay. In immunocompromised people, however, viruses are more likely to cause malignancies.

One approach to control EBV infection is by interfering with the complex and dynamic patterns of how viral genes are switched on or off — a process known as gene expression. The Tempera lab has explored the role of gene expression in the regulation of EBV latency, unveiling some viral and host cell factors that play key roles in regulating these patterns.

An EBV protein called latent membrane protein 1 (LMP1) is essential for the virus’s ability to make B cells cancerous.

The Tempera lab studies just how this protein affects the host cells. They discovered that LMP1 affects the function of an enzyme called poly(ADP-ribose) polymerase 1 (PARP1) and that inhibiting this protein suppresses malignant transformation, uncovering an important role of PARP1 in EBV-induced oncogenesis.

In a recent paper1, Tempera and colleagues demonstrated that LMP1 causes a switch in how infected cells produce the building blocks of fat that support tumorigenesis and cancer progression. Researchers also showed that targeting these metabolic changes could be an effective therapeutic strategy to treat EBV-associated cancer and that PARP1 inhibitors offset the metabolic changes caused by LMP1 that drive tumorigenesis.

“We have uncovered a potential new use for PARP inhibitors, which are currently used to treat recurrent ovarian cancers in women who have defects in their DNA repair system,” said Dr. Tempera. “Repurposing existing drugs saves time and money in the process of creating new therapies.”

Dr. Tempera joined Wistar as an associate professor in 2020, but that was not his first time working at the Institute. He had trained as a postdoctoral fellow in the Lieberman lab, which helped him launch his career in cutting-edge research on the epigenetic mechanisms underlying EBV infection. Returning to Wistar with his lines of research as an established investigator, he strengthened our program on virology and cancer.

“The outstanding scientific environment and technological support that benefited me during my training are a strong asset to further expand my research program.”

The lab of his mentor Dr. Lieberman is a reference point for EBV research as they have made seminal discoveries in the field and described several mechanisms that control replication and gene expression in latent EBV infection. One focus of their research is the Epstein-Barr nuclear antigen 1 (EBNA1) protein that is essential for efficient viral DNA replication. The team has been pursuing the development of small molecule inhibitors of EBNA1 as potential treatment against EBV-associated malignancies.

One of the lab’s latest studies2 led to an important basic discovery in the field, expanding the understanding of EBNA1’s function and providing new possibilities for inhibiting EBNA1 activity as an anticancer strategy.

The link between virus infection and human cancer is a complicated matter to unravel and has been studied for more than 100 years. The research underway in the Tempera and Lieberman labs is crucial to understanding the role viruses play in malignant transformation and hopefully finding future treatments to halt this process.

1 Epstein-Barr Virus-Encoded Latent Membrane Protein 1 and B-Cell Growth Transformation Induce Lipogenesis through Fatty Acid Synthase, J Virol, 2021
2 Cell-cycle-dependent EBNA1-DNA crosslinking promotes replication termination at oriP and viral episome maintenance, Cell, 2021

Caspar Wistar Fellows Drs. Ami Patel, Rahul Shinde, and Daniel Claiborne post with the Briggs

Expanding the Caspar Wistar Fellows Program

Written by The Wistar Institute on September 3, 2021. Posted in Featured News.

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!

(left) Dr. Amelia Escolano (right) Dr. Nan Zhang

The Wistar Institute Recruits Vaccine Researcher Amelia Escolano, Ph.D., and Immunologist Nan Zhang, Ph.D., as Assistant Professors

Written by The Wistar Institute on September 1, 2021. Posted in Press Releases.

PHILADELPHIA — (Sept. 1, 2021) — The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, welcomes Amelia Escolano, Ph.D., and Nan Zhang, Ph.D., as assistant professors.

Escolano’s research focuses on the development of novel vaccine approaches against highly mutating viruses. She will join the Vaccine & Immunotherapy Center.

“My laboratory will investigate the immune responses elicited by a new form of vaccination that involves sequential immunization. Our goal will be to identify guidelines for the design of efficacious vaccines that induce broad protection for prolonged periods of time,” said Escolano. “I also plan to establish collaborations with members of Wistar’s Cancer Center in order to explore the use of our sequential vaccination approaches against cancer-related viruses and tumor neoantigens.”

Zhang, who joins the Immunology, Microenvironment and Metastasis Program of The Wistar Institute Cancer Center, studies the role of a group of white blood cells known as macrophages during ovarian cancer metastasis in the abdominal cavity.

“Because of recent developments in macrophage research, these cells are known to be highly plastic and heterogenous, meaning that depending on their surrounding environment they can either promote or suppress tumor growth and form different subgroups that are very difficult to identify and to target pharmaceutically,” said Zhang. “My lab will use cutting-edge technologies to better understand the functional differences among these macrophage subgroups and eventually find a treatment plan for this devastating disease.”

“We are delighted to be able to recruit top talent to our scientific community,” said Dario Altieri, M.D., Wistar president and CEO, director of The Wistar Institute Cancer Center and the Robert and Penny Fox Distinguished Professor. “Nan and Amelia have outstanding research records in finding answers to some of the most pressing and timely questions in cancer and HIV, and have done so using cutting-edge models and technologies. We can’t wait to witness their potential unfold and to see what new research frontiers they will conquer.”

“I’m excited to join an institution with such an important history of contributions to the vaccine design field and where my research can synergize with that of other outstanding members of the Vaccine & Immunotherapy Center,” said Escolano. “I am thrilled to have the opportunity to develop my own scientific ideas and create a community of researchers around them. It is my goal to transmit my passion for science to the new generations and train a solid group of researchers who will significantly influence scientific progress.”

“I have always admired the collaborative, world-class research environment at Wistar, particularly in cancer biology and immunology, and thought the Institute would be a perfect fit for me given my mutual research interests with other investigators,” Zhang said. “I feel like I’m about to embark on some of the most thrilling adventures one could ever have — making new discoveries that can potentially save people’s lives and mentoring next-generation scientists.”

Escolano earned her B.S. from the University of Oviedo, Spain, and University of Turku, Finland, and a master’s degree from Centro de Biología Molecular Severo Ochoa, Madrid, and Genome Research Institute (GRI), Cincinnati, Ohio. She obtained her Ph.D. in biochemistry and molecular biology from the Spanish Center for Cardiovascular Research, Madrid, and Autonoma University, Madrid, and completed her postdoctoral training at The Rockefeller University, New York.

Zhang received his B.S. in microbiology and immunology from Shandong University, China, and a Ph.D. in biochemistry and molecular biology from the University of Oklahoma Health Sciences Center. He completed his postdoctoral training in the Department of Pathology and Immunology of Washington University School of Medicine.

###

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.org.