__MAIN_TEXT__

Page 1

Focus Winter 2020

O N

T H E

W I S TA R

I N S T I T U T E

W I S TA R S C I E N C E : B O L D. I M A G I N AT I V E . I N S P I R E D.

A New Generation of Cancer Researchers at Wistar

From the Cancer Center

Breaking Down the Science of the MMR Vaccine

News From the Institute

Education


COVER STORY

A New Generation of Cancer Researchers at Wistar A conversation with the latest Cancer Center additions

E

xpanding the faculty and enhancing its multidisciplinary nature are focal points in Wistar’s Cancer Center under the leadership of Dario Altieri, M.D., president and CEO, director of The Wistar Institute Cancer Center, and Robert and Penny Fox Distinguished Professor. The recent recruitment efforts, supported by partners such as The Pew Charitable Trusts, were inspired by the idea that junior investigators—in their peak of scientific productivity and creativity—are most likely to generate cutting-edge research. Therefore, attracting the most brilliant scientists and persuading them to launch their laboratory at Wistar positions the Institute ahead of a trend that is becoming increasingly popular in many research institutions. In the span of one year from 2015 to 2016, four assistant professors joined the Cancer Center, thereby enriching and complementing existing programs with new expertise and fresh perspectives:

1

Qing Chen, M.D., Ph.D., came to Wistar from Memorial Sloan-Kettering Cancer Center and started her lab researching the mechanisms of brain metastasis, a very challenging subject that is in urgent need of advancement. Alessandro Gardini, Ph.D., an ‘old acquaintance’ of Wistar’s, began his postdoctoral training in a Wistar lab and completed it at the University of Miami. He studies genomics and epigenetics, or how our genome is decoded and how malfunctioning mechanisms can cause cancer. Kavitha Sarma, Ph.D., came from Harvard Medical School. She is a biochemist and an epigenetics expert. Her current focus is in understanding how certain RNA molecules help shape the structure of chromatin, the combination of DNA and protein that makes up chromosomes, and elucidating the role of these mechanisms in cancer and other diseases.

Focus on The Wistar Institute


In the span of one year from 2015 to 2016, four assistant professors joined the Cancer Center, thereby enriching and complementing existing programs with new expertise and fresh perspectives. Zachary Schug, Ph.D., a Philadelphia native who received his postdoctoral training across the ocean at the Beatson Institute in Glasgow, U.K., returned to Philadelphia to launch his research program at Wistar in cancer metabolism, looking at the mechanisms that support the high nutrient demands of tumor growth. Four years after arriving, and well-settled at Wistar, these four assistant professors have made significant progress establishing research programs, publishing their first papers as senior authors, and securing solid funding through federal grants and private foundations, such as the W. W. Smith Charitable Trusts, the American Cancer Society, Susan G. Komen, the V Foundation for Cancer Research, and The G. Harold & Leila Y. Mathers Foundation. We brought the four scientists together to take stock of their experiences at Wistar. A diverse and stimulating scientific environment

One of the common themes in the conversation was the intellectual and scientific support junior investigators receive at the Institute. “Wistar is a small place with exceptional scientific diversity,” said Gardini. “Exposure to different expertise in a highly collaborative environment has created plenty of opportunities for me to expand my scientific horizon and skillset,” added Schug. “For example, because of the outstanding immunology community we have at the Institute and the frequent seminars they host, my knowledge of immunology has expanded dramatically, and that was an area in which I wanted to grow.” “I kept myself distant from immunology until I joined Wistar; it wasn’t my favorite field,” joked Chen. “But no cancer biologist can stay away from immunology these days, especially if you study the tumor microenvironment like I do. Being at Wistar made that transition easier for me.”

Pursuing their projects and expanding their interests

When asked if they stayed their course and followed their original research plan, all four scientists said they are working on the overall ideas they proposed, but they’ve added new directions they can now pursue because of the expertise and support of other labs at the Institute. “My drug development project was difficult to get off the ground,” said Schug. “At Wistar, though, through collaboration with Dr. Salvino, I took a different approach that was successful.” When you are a basic research scientist, finding good model systems to test your hypothesis can really make a difference. “I felt safe exploring the ovarian cancer model because there is a lot of expertise in Dr. Zhang’s lab, in particular, and I can count on resources for future developments,” added Gardini. “Even though my primary interest is breast cancer, I received a lot of mentorship from Dr. Weeraratna,” said Chen. “She brought me into melanoma—a great model to study brain metastasis because of its tendency to invade the brain. As a matter of fact, nearly 40% of melanoma patients develop brain metastasis.” What about academic freedom, we asked. Everyone said they were given leeway to choose their scientific direction and explore their ideas. Sometimes, access to funding can bring about involuntary restraints to the scientists’ ability to pursue their interests. “Access to funds for basic researchers can be a challenge because most of the money is diverted to applied research,” said Sarma. “My work is clinically relevant, so I don’t necessarily face this issue,” added Chen. “Yet, I can’t wrap my head around the scarcity of funding for basic research, as it creates the foundations for clinical development.”

Winter 2020

2


Drs. Qing Chen, Alessandro Gardini, Zachary Schug, and Kavitha Sarma.

“I appreciate the Institute’s strategy for grant submission because we are not pushed to apply to every possible opportunity, but they encourage us to focus our efforts where we are stronger and have a better chance of success,” said Gardini. “In the long run, it’s an efficient approach and avoids putting too much pressure on the junior faculty members.” A little weight off their shoulders

Technological and administrative support were also highly rated and considered crucial for growth and success. “Wistar has a reputation for its core facilities, and they absolutely lived up to my expectations,” said Gardini. “Besides the quality of their work, their efficiency and fast turnaround help getting answers fast and moving the projects forward.”

3

“Dario kept his promise in terms of equipment and facilities,” said Schug. “Having a metabolomics core was a necessity for the research I wanted to pursue, and he and other professors worked with me to secure funding for new state-of-the-art instrumentation. Dario has been very supportive of me setting up new techniques at the Institute.” Administrative support is very important for junior principal investigators who are starting to navigate grants and budget, and managing multiple projects and tasks at the same time. “The support we receive from the administrative departments is exceptional, it makes our lives easier so we can focus on the science as much as possible,” said Sarma.

Focus on The Wistar Institute


“The support we receive from the administrative departments is exceptional, it makes our lives easier so we can focus on the science.” —KAVITHA SARMA, Ph.D.

From the Chen lab: Microscopic image of metastatic cancer cells (pink) in the brain. Brain vascular structures are labeled in cyan.

Beyond Wistar

A home for basic research

Expanding beyond Wistar’s walls and into the Philadelphia life sciences hub, there was consensus that, with so many academic research institutions and hospitals, most of which are expanding, Philadelphia is the place for biomedical scientists. “I have ongoing collaborations with nearly all the major cancer centers in Philadelphia at this point,” said Schug. “It’s as easy as going across the street or taking a walk downtown.” “If my projects lead me in a new direction that I want to explore, there is a very high chance I’ll be able to find someone around who can help,” added Gardini. The private biotech arena is also bourgeoning in Philly. “I’m not quite there yet,” said Schug. “Though I definitely see my research expanding in that direction. We are actively engaged in drug development and testing our compounds in preclinical models with the hope that in a year from now we may begin searching for a biotech or pharmaceutical company with which to partner. Fortunately, Wistar has a fantastic business development team that supports us throughout this process.” “I’m not exposed to biotech now, maybe in the future, if my studies identify new therapeutic targets,” said Chen. “Alessandro and I are a little less likely to benefit from it because of the basic nature of our science and the fact that the biotech industry in Philadelphia is geared towards drug development. Naturally, it can have a bigger impact on translational scientists,” said Sarma.

Bringing basic investigators on board reflects Wistar’s everlasting commitment to fundamental research and the type of breakthroughs that can come from it. In addition to expanding the universal knowledge of biological mechanisms, basic discoveries point to new therapeutic targets that can be drugged, while bringing about technological advancement. “Genomics is a very technology-driven field,” said Sarma. “I’m excited to witness and participate in this trend and always thrilled to see new technologies emerge that will allow us to explore biological phenomena and disease in greater depth.” “We can now look at things in ways scientists have never before, we can do genomic analysis at the single-cell level, which is mind-blowing.” added Gardini. “Obviously, this also makes our work challenging, because we need to keep up with the fast pace of technology and stay abreast of new developments and incorporate them in our research in meaningful ways.” A look at the future

“I am very excited about the developments of my research on how diet, metabolism, microbiome, and epigenetics talk to one another in cancer,” said Schug. “Speaking of new technologies, we have been advancing new tools to study the organism as a whole and I am eager to apply this new approach to my research at Wistar.”

Winter 2020

4


“We root for each other’s successes and celebrate each other’s accomplishments, which is not to be taken for granted. This reflects positively on the way I feel about Wistar.” —ALESSANDRO GARDINI, Ph.D.

“I’m happy that more labs are working on brain metastasis, and I look forward to more neurobiologists entering the field,” said Chen. “Looking at things just from the cancer angle is limiting, we can move forward much faster when we know the underlying physiology.” “Cancer genomics studies in the past decade have highlighted that many transcriptional and chromatin modulators are mutated in cancer, and for the vast majority of these we don’t know what their role is,” said Gardini. “The field is getting more and more competitive, but I’m excited that there is so much room to explore and figure out new mechanisms, and with that also come growing funding opportunities.” “I get excited about every new discovery, big and small,” said Sarma. “Having the first piece of data and looking at it for the first time is a lot of fun, and I look forward to more of these moments. I love figuring out how things work, solving puzzles, making sense of unexpected results. That’s the best part of my job.”

“I’ve received a lot of help on grants applications from these guys,” said Schug. “We exchange tips and learn from each other’s experiences.” “We root for each other’s successes and celebrate each other’s accomplishments, which is not to be taken for granted,” said Gardini. “This reflects positively on the way I feel about Wistar.” “We don’t just talk about science, though,” said Sarma. “We discuss work-life balance, vacations, and our lives and hobbies outside the lab.” “I’m going to say that food is probably our most typical conversation subject,” interjected Gardini, and they all acknowledged that with a laugh. ■

The gang

Maybe it’s because they arrived within a few months of each other, or maybe it’s because they are all first-time independent investigators launching their career in academia together, and it’s certainly because they get along well—but the fab four have formed a strong bond. “Besides collaborating scientifically, I think we’ve created a support system for each other,” said Sarma. “We interact daily and make time to connect and discuss each other’s strategies and little bumps in the road.” “They have dragged me out of my shell, and I’m glad they did that,” said Chen. “Someone will check if they haven’t seen me for a while.”

5

Focus on The Wistar Institute


BREAKING DOWN THE SCIENCE

Vaccination Exploration: The Case of Measles, Mumps and Rubella Getting sick with these childhood diseases could mean much more than a fever and a rash A brief history of vaccination

Infectious diseases have existed alongside (and within) humans throughout history. Efforts to prevent contagion have been attempted since before the discovery of our immune system and the pathogens that try to invade it. The practice of immunization is based on the idea of exposing the body to a weakened or dead infectious agent (or part of it) to induce a mild version of the disease that the host is able to fight off, remaining protected at the next encounter. Variolation—injecting material from a smallpox patient’s sore into a healthy person’s arm to protect against smallpox—was common practice starting in the 17th century in China, the Middle East and Africa, and well before Edward Jenner created the first modern vaccine in 1798.

Jenner observed that milkmaids who had been infected with vaccinia virus (the cause of cowpox in cows) did not get sick with smallpox. He was able to achieve immunization against smallpox by inoculating people with the vaccinia virus—hence the terms “vaccination” and “vaccine.” This first empiric vaccine laid the foundation for the development of many other vaccines over the course of the 19th century. Scientists fine-tuned the technology to make vaccines safer and more effective. In the 20th century, isolation of many infectious agents together with progress in immunology, cell culture and molecular biology, allowed for the advent of more vaccines that have saved millions of lives and changed the course of human history.

Winter 2020

6


Spotlight on the mumps, measles and rubella vaccine (MMR)

The Wistar Institute developed the rubella vaccine that is currently given to children in the U.S. and many other countries as part of the MMR trivalent vaccine, which provides protection against mumps, measles and rubella. Licensed by Merck in 1971, this vaccine combined the three existing vaccines into one and dramatically curbed three childhood infections that affected millions in the pre-vaccine era and were associated with severe complications and death. The Wistar rubella vaccine is also contained in the MMRV vaccine ProQuad licensed by Merck and approved in the U.S. in 2005, which also protects against varicella virus (chickenpox). MEASLES

Measles is a highly contagious disease that causes fever, respiratory symptoms and a rash. In a small percentage of cases, it can result in serious complications and death, especially in young children, pregnant women and immunocompromised individuals. Complications include pneumonia, which is the most common cause of death from measles in young children and occurs in one out of every 20 infected children; encephalitis, or swelling of the brain, that can lead to convulsions, deafness or intellectual disability and affects one child out of every 1,000 infected; and premature or low-birth-weight babies in pregnant women. Dr. Stanley A. Plotkin working at Wistar.

7

The rubeola virus that causes the measles was isolated in 1954, after which several generations of vaccines were developed. In 1968, the final (and current) version of the attenuated vaccine was created and since then has contributed to measles cases plummeting in the U.S. In 2000, endemic measles was declared eliminated. Yet in recent years measles has returned with several outbreaks happening in the U.S. and beyond, linked to falling immunization rates in certain groups. MUMPS

Mumps is a very contagious viral infection that manifests with swelling and pain in the salivary glands, fever, headache, muscle aches, and fatigue. In the vast majority of cases mumps causes very mild symptoms, but in rare cases it can lead to serious complications. These include meningitis, an inflammation of the brain and spinal cord membranes; hearing loss; encephalitis; and orchitis, or the inflammation of testicles, which occurs in one third of boys infected with mumps. In 1963, the mumps virus was isolated, and a vaccine was licensed in 1967 that has contributed to a more than 99% decrease in mumps cases in the U.S. RUBELLA

Rubella, or German measles, usually manifests with mild symptoms and a red rash but is associated with severe complications in pregnant women, known as congenital rubella syndrome (CRS). CRS can cause miscarriage, stillbirth and birth defects such as heart problems, loss of hearing and eyesight and intellectual disability. In 1964, a major rubella outbreak started in Europe, crossed the Atlantic Ocean and swept into the U.S., infecting 12.5 million, killing 2,000, causing 20,000 cases of CRS, and leading to thousands of miscarriages and children born with birth defects. The first rubella vaccines used in the U.S. were licensed in 1969/1970. At the same time, another vaccine developed at Wistar in the laboratory of Stanley A. Plotkin, M.D., was licensed in Europe. The Wistar-developed vaccine proved to be more effective and have a better safety record than the others, leading the U.S. to switch in 1979. Plotkin’s vaccine is still used today and is the only rubella vaccine currently licensed in U.S. With critical support from the Bill & Melinda Gates Foundation, Wistar is now working with external collaborators to expand and archive the research-grade rubella virus seed stock in order to provide companies with GMP materials to produce new vaccines, increasing distribution around the world and bolstering supply security.

Focus on The Wistar Institute


The MMR vaccine is very effective against measles: two doses are about 97% effective while one dose is about 93% effective.

Measles resurgence

The MMR vaccine is very effective against measles: two doses are about 97% effective while one dose is about 93% effective. Yet, measles has been on the rise globally, leading to a public health alert. The World Health Organization reported that there were more cases of measles in the first half of 2019 than in any year since 2006. In the first half of 2019 in the U.S. alone, there have been 1,182 measles cases across 30 states—a high in the last 25 years. There are many reasons for this resurgence. Because measles is highly contagious, it is estimated that 95% of people need to be vaccinated in order to protect the population from outbreaks—a concept called herd immunity. Current U.S. vaccination rates are holding around 91% and more children in Europe are being vaccinated than ever before, but these rates are still under the required threshold, therefore the population is still vulnerable to outbreaks.

Healthcare inequality also puts children in medically underserved families at higher risk of infection. Therefore, while measles has a tendency to resurge in populations with a lower than 95% vaccine coverage, pockets where vaccination rates are lower than the nation’s average offer breeding ground for the virus to spread undisturbed. MMR safety

Rigorous studies have confirmed that the MMR vaccine is very safe and overwhelmingly debunked reports of any association with autism in children. As with all medicines, vaccines may have side effects. The MMR vaccine has been associated with mild and temporary side effects including rash, fever and headache. More serious adverse events, including seizures, are very rare and not associated with long-term effects. Allergic reactions are also rare. The risk to benefit ratio is such that getting the MMR vaccine is much safer than getting measles, mumps or rubella. ■

Vaccination rates and measles outbreaks

But why is the measles resurgence happening now if the vaccination coverage has been stable or improved in recent years? This could be partly due to the nature of highly contagious diseases that tend to spread in wave-like cyclic patterns. On the other hand, statistical and epidemiological analysis indicate a correlation between a decrease in vaccination coverage and measles outbreaks. In fact, several outbreaks have been reported in close-knit communities with particularly low vaccination rates due to vaccine skepticism or refusal for religious or philosophical reasons. In those cases, travelers brought measles back from other regions where large outbreaks were occurring, and infection spread fast among unvaccinated people.

Glossary Endemic infection

Constantly maintained at a baseline level in a geographic region without external inputs, or cases imported from other areas or countries. Herd immunity or community immunity

When enough people are vaccinated against a disease, the infection can’t spread as easily from person to person; as a consequence, the entire community is less likely to get the disease and even individuals who can’t get vaccinated will have some protection from getting sick. Herd immunity also limits the chances of an outbreak in case someone in the community does get sick, because it’s harder for the disease to spread.

Sources Centers for Disease Control; Historyofvaccines.org; World Health Organization; WHO Europe; Institute for Vaccine Safety, Johns Hopkins University School of Public Health.

Winter 2020

8


BREAKING DOWN THE SCIENCE

Coming of Age: The Creation of the HPV Vaccine

Each Women & Science program tackles a foremost health topic that affects women and therefore their families and loved ones. Our next event will feature immunotherapy expert Dr. Padmanee Sharma from The University of Texas MD Anderson Cancer Center. Pushing The Envelope in Cancer Immunotherapy LEARN MORE AT wistar.org/womenandscience

Radio personality Maiken Scott, host of WHYY’s The Pulse, led a riveting discussion by thought leaders in the field of HPV vaccines, Dr. Kathrin Jansen, Pfizer senior vice president and head of Vaccine Research and Development, and Dr. Iona Munjal, a director in Pfizer’s Vaccine Clinical Research and Development Team. The fireside chat laid the historical groundwork in their roles to develop, design and roll out the world’s first HPV vaccine. A heavy burden for global health

HPV is the most commonly sexually transmitted virus in the world, infecting 80% of sexually active adults in their lifetime1. HPV infection has a dramatic impact on global health, with more than 500,000 cervical cancer cases diagnosed worldwide each year, the vast majority of which (around 85%) occur in the less developed regions2 where no screening programs are available, and women are diagnosed at late stages. Globally, cervical cancer causes more than 260,000 deaths each year2. HPV also causes genital warts and cancers such as head and neck cancers, and men get HPV-related throat cancer as often as women get HPV-related cervical cancer.

9

Focus on The Wistar Institute


“We had to get back to basics and normalcy regarding this vaccine” —IONA MUNJAL, M.D.

Vaccine reception

Dr. Kathrin Jansen discussing the burden of HPV-related diseases.

Making the HPV vaccine: challenges and persistence

“This is the story of great scientific discovery, grit and persistence, and the breaking of dogmas,” said microbiologist and vaccinologist Dr. Jansen. Jansen took the audience back to the 1990s to describe the Human Papillomavirus (HPV) life cycle when HPV was identified as the root cause of cervical cancer. She spoke of German virologist Professor Harald zur Hausen, who went on to win a 2008 Nobel Prize in Physiology or Medicine for revolutionizing cervical cancer research by discovering HPV DNA in cervical cancer biopsies, and translating the role of human papilloma viruses in cancer. A seminal study in 1999 confirmed that HPV is a necessary cause of cervical cancer, as virtually all cervical lesions (99.7%) contain HPV DNA3.

Jansen recounted how the early phases of vaccine development were surrounded by skepticism and it took much perseverance to overcome the technical challenges. In the process, she and the other scientists working in the HPV field broke some scientific dogmas, showing for example that, contrary to the common assumption that cancer development by HPV takes decades, it occurs relatively quickly (within 1-5 years from infection), which allowed for testing the vaccine effectiveness in a reasonable timeframe. In several clinical studies the vaccines currently available showed excellent safety profiles and a remarkably high efficacy against cervical cancer. Complete prevention of virus infection, referred to as sterilizing immunity, was also demonstrated by the HPV vaccine, breaking another dogma that considered this an elusive goal.

Winter 2020

Despite its extraordinary effectiveness in preventing cervical cancer, the HPV vaccine had to fight some initial backlash caused by prejudice and confusion. “HPV being a sexually transmitted disease overshadowed the importance of this vaccine as a cancer prevention strategy, which is far more significant and the ultimate goal of vaccination,” said Munjal, who is a pediatric infectious disease doctor. “This vaccine was 90% effective against HPV and we had so much joy because this vaccine can eventually eradicate HPV-related cancers. But we just saw the numbers and missed the story. We had to get back to basics and normalcy regarding this vaccine. Pediatricians had to give this vaccine as they did the rest of the recommended vaccines—treat it exactly the same. It’s a revolutionary change that we’ve lived through and learned from.” That the vaccine protected against cancer and genital warts made it a hot button issue tied to sexually transmitted disease and the myth that the vaccine would somehow encourage or endorse promiscuity among teenagers. Munjal also discussed different vaccine rollout strategies in other countries.

10


“Right now HPV vaccine uptake is at 50%, but in Australia and the United Kingdom, the disease burden is dropping,” said Munjal. “By 2030, Australia could reduce cervical cancer by 90%. They were able to do it because it’s a school-based health campaign which shows the effectiveness of bringing care to where people are.” Stories behind women in science

In the background of the HPV vaccine discussion, the two scientists told their personal stories as women in science and how they live through the challenges of their work. Jansen, as a young Ph.D. student in Germany, visited a pharmaceutical facility in which a male “tour guide” asked her group of young women why they were on the tour. He implied they were not going to pursue jobs in science and would pursue less rigorous jobs or marry and have a family. She was appalled by that comment but did not let it influence her and she went on to become a highly successful scientist.

L-R: Drs. Iona Munjal and Kathrin Jansen.

Then she discussed her work in the pharmaceutical industry, guided by passion, perseverance and intuition. Hired for one project, she switched to work on an HPV vaccine when the opportunity arose, and ended up leading the development of the first HPV vaccine called Gardasil while working at Merck. But, her scientific career is quite possibly traced to when she was a child. “I was a sick child and my parents gave me antibiotics—what I thought were magic drugs—to make me feel better and that’s why I pursued translational science, to make people feel better and treat disease,” said Jansen. “Then I had great sponsors throughout my career—people who have had confidence in me and have endorsed me. I’ve always found supportive people.” Munjal’s career as a physician scientist was also inspired from when she was a little girl. “My grandmother was a physician scientist and we always said she raised the women in the family to follow her path,” said Munjal. “I consider science a way to express my creativity and draw my resilience from the trust my family has in me and my work.” In 2006, Merck’s HPV vaccine Gardasil was approved in the U.S. It protects against HPV types 6, 11, 16 and 18, preventing 70% of cervical cancers, and the majority of HPV-induced cancer cases and genital warts. In 2014, an expanded vaccine Gardasil 9 was approved. One of the most important advances in cancer prevention, the HPV vaccine is safe and effective. It is recommended for people from 11 to 26 years old and available to adults up to 45 years old who are at risk. Yet, vaccine rates in the U.S. for girls and boys from 13 to 17 years old still hover between only 48.6% to 51%1. About 14 million people contract HPV each year in the U.S., and 92% of these infections are caused by vaccine-preventable strains1. The United States has the capability to eradicate HPV and by doing so has the opportunity to wipe out cervical cancers and six other cancers related to HPV. We still need new methods to screen for HPV and improve treatment on pre-cancerous lesions. The Healthy People 2020 campaign, the federal government’s statement of national health objectives, wants complete vaccination for more than 80% of female and male teenagers ages 13-15 by 20204. ■

Sources 1. Centers for Disease Control (CDC) 2. International Agency for Research on Cancer (IARC) 3. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. 1999 Walboomers J.M. et al, J Pathol. 4. healthypeople.gov

11

Focus on The Wistar Institute


NEWS FROM THE INSTITUTE

Wistar Launches New Studies on the Link Between Treatment for Opioid Abuse and Health Outcomes of People Living With HIV

L-R: Dr. Luis J. Montaner with lab members Dr. Krystal ColonRivera and Carlos Carmona.

W

istar’s HIV program is well known for its efforts to find a cure for HIV. The team of Luis J. Montaner, D.V.M., D.Phil., Herbert Kean, M.D., Family Professor and director of the HIV-1 Immunopathogenesis Laboratory at the Vaccine & Immunotherapy Center, is now launching a new area of investigation to study the impact of opioid use disorder (OUD) and medications for opioid use disorder (MOUDs) on immune recovery in response to antiretroviral therapy (ART) in HIV-infected people. Spearheading an international multidisciplinary clinical research consortium, the Montaner lab recently received two major grants totaling more than $12 million from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

Previous results have uncovered a potential link between substance abuse, HIV infection and MOUDs that may affect health outcomes of people living with HIV and taking ART. The team hopes to get to the bottom of this link. Both HIV infection and chronic opioid exposure are associated with immune activation, a condition that leads to acquired immunodeficiency syndrome (AIDS). OUD is commonly treated with different classes of drugs that either activate or block the opioid receptor and may have different effects on inflammation and immune activation. A deeper knowledge of these interactions could inform what types of MOUD are best used in combination with ART, with important impact on health and mortality. “We are leading this collaborative global effort from Philadelphia and expect the results to have broad clinical implications informing the best pharmacologic strategy for the management of opioid use disease in HIV-infected people starting ART,” said Montaner. “In light of the ongoing opioid epidemic in our nation, this study is relevant to ensure that the right medications are used for both HIV and OUD, with the ultimate objective of saving lives in the future.” With support from NIDA, the consortium will conduct two clinical studies. The first one, in collaboration with partners in France, Vietnam and at the University of Pennsylvania, will compare recovery outcomes and adherence to ART therapy in participants with OUD who receive either methadone, extended-release naltrexone or buprenorphine.  The second study will be conducted locally in collaboration with University of Pennsylvania, Jonathan Lax Treatment Center, and the Icahn School of Medicine at Mount Sinai and will investigate the mechanism of immune activation in response to MOUD. ■

Winter 2020

12


E D U C AT I O N

Wistar’s Biomedical Research Technician Apprenticeship Named the 2019 Outstanding Non-traditional Apprenticeship Program by the PA Department of Labor & Industry

D

uring the second Annual Pennsylvania Apprenticeship Summit, Wistar’s Biomedical Research Technician (BRT) Apprenticeship was named the 2019 Outstanding Non-traditional Apprenticeship Program by the Pennsylvania Department of Labor & Industry.  Eileen Cipriani, deputy secretary for Workforce Development of the Pennsylvania Department of Labor & Industry and event host, reminded all Summit attendees of the need for workforce development opportunities with equity and inclusion and highlighted Wistar for creating the country’s first biomedical research apprenticeship program. William Wunner, Ph.D., director of Academic Affairs, Outreach Education and Technology Training, and Brian Keith, Ph.D., dean of Biomedical Studies, accepted the award and spoke to the incredible opportunities both pre-apprenticeship and non-traditional apprenticeship programs bring to the region, especially for budding areas in the life sciences industries and research institutions as well as other new technological sectors. The Summit emphasized the Commonwealth’s commitment to creating new training opportunities that connect jobseekers with highly specialized jobs. Nontraditional apprenticeships serve the community by applying the model used by skilled trades to place highly trained, qualified workers into the job market. Formally approved by the Pennsylvania Department of Labor & Industry in 2017, Wistar’s BRT Apprenticeship program is the first registered, non-traditional apprenticeship program in the biomedical sciences in the nation. By leveraging collaborations between the Institute and research partners in biotech, biopharmaceutical, and academic research settings, the BRT Apprenticeship program offers hands-on, highly specialized technical and professional training toward becoming biomedical research specialists and professionals. 

13

L-R: Eileen Cipriani, deputy secretary, Workforce Development, PA Dept. of L & I; Drs. William Wunner and Brian Keith; Eric Ramsay, director of the Apprenticeship and Training Office, PA Department of L & I.

The BRT Apprenticeship is part of the Institute’s signature workforce development and training programs, which started in 2000 with the creation of the Biomedical Technician Training (BTT) Program through Wunner’s efforts in partnership with the Community College of Philadelphia. At Wistar, Wunner, Keith and Kristy Shuda McGuire, Ph.D., Wistar’s new associate dean of Biomedical Studies, oversee a portfolio of diverse education and training programs geared to all ages and academic backgrounds. From standout students attending the Philadelphia School District high schools, to Community College of Philadelphia students training to be biomedical lab technicians, to graduate students working in Wistar labs to complete their theses for a Ph.D., and postdoctoral fellows preparing for independent research careers, the Institute has focused on offering the highest levels of classroom and hands-on training. Through each and every trainee, Wistar’s biomedical education and training programs expand the life sciences workforce and strengthen the research culture in the region. ■

Focus on The Wistar Institute


New International Frontiers in Science Education

T

his past fall, Wistar formalized an agreement with Leiden University Medical Center (LUMC) in the Netherlands to establish the Wistar-Schoemaker International Postdoctoral Fellowship and bring recent LUMC Ph.D. graduates to Wistar for their postdoctoral training. This program will promote scientific exchange between investigators at the two institutions, expand the Institute’s international partnerships in research and education, and open new opportunities for global collaboration and scientific and business exchanges between the Netherlands and the U.S. The Wistar-Schoemaker Fellowship builds on the legacy of mentorship, determination and innovation of the late biotechnology entrepreneur Hubert J.P. Schoemaker, Ph.D., a native of the Netherlands who in 1979 co-founded Centocor, now Janssen Biologics. Centocor advanced Wistar’s seminal research in monoclonal antibodies into a commercial platform and was one of the nation’s first and largest biotechnology companies. Schoemaker also built Centocor facilities in the Netherlands in what is now the Leiden Bio Science Park, one of the top five science parks in Europe. The Wistar-Schoemaker Fellowship builds on the historical connection between Wistar and the Dutch biomedical research arena. Schoemaker’s wife Anne was instrumental in the process of establishing the Wistar-LUMC partnership and the Fellowship, inspired by his passion for mentoring the next generation of investigators to advance scientific achievement in the interest of helping people. ■

Winter 2020

The Wistar-Schoemaker Fellowship builds on the historical connection between Wistar and the Dutch biomedical research arena.

L: The University of Leiden. R: Drs. Pancras Hogendoorn, dean of the Leiden University Medical Center, and Anita Pepper, Wistar Vice President of Institutional Advancement, signing the memorandum of understanding for the Wistar-LUMC partnership.

14


Events Highlights The Wistar Gala—A Celebration of Science S AT U R DAY, N OV E M B E R 2

Held at the Pennsylvania Academy of the Fine Arts and hosted by CBS Philly health reporter Stephanie Stahl, the 2019 Wistar Gala honored the legacy of philanthropist and long-time Wistar supporter Fran Tobin. Guests learned about the work of early-career Wistar scientists through five-minute “speed science” sessions and peering at samples through the microscope. After dinner, they enjoyed “Betting on Wistar Science”, a full-fledged casino, featuring multiple dealers and games. This was one of Fran’s favorite forms of entertainment, and it was enjoyed by all throughout the night. A special thank you to our top sponsors: Flyers Charities; Ellen & Ron Caplan; Jill & Mark Fishman; Robert & Penny Fox; David, Matthew, Eli, Sara, & Jacob Kestenbaum; Sharon & Joseph Kestenbaum; Rose Glen Advisors, LLC; Adele Schaeffer; Pam & Tony Schneider; The Tobin Family Foundation; Veolia; Dr. Susan Dillon & Dr. William Wong; Ruth & Richard Horowitz; and Dan Wheeler & Amy Fox. ■

Clockwise from top: Stephanie Stahl; Steven Abramson and Dr. Vito Rebecca; Stephanie Stahl and Sharon Kestenbaum shared a moment with the Flyers Wives and staff—Rita Johansson, Donna Ashbee, Vickie Samuelsson, Lisa Hanrahan, Diana Therien, Janice Terry and Doreen Holmgren; Fran’s family enjoying the games.

15

Focus on The Wistar Institute


HO NO RIN G FRAN TOBIN Fran was a long-standing and steadfast champion for Wistar, raising funds for cancer research, supporting the building of the Robert and Penny Fox Tower, and introducing new friends and contributors to the Institute. She was ahead of the curve, understanding that real medical advances and cures can only be made through research discoveries. We will never forget Fran’s spark for life, wonderful sense of humor, and dedication to Wistar.

Clockwise from top left: Drs. Galina Semenova, Maria CecĂ­lia Nunes, Anita Pepper, and Ekta Agarwal; Helen Pudlin, Stephanie Stahl, Lynne Tobin, Sharon Tobin Kestenbaum, Steven Tobin, and Dr. Dario C. Altieri; Katharine and Louis Padulo; Claire & Michael Greenwood; Joshua Parris explains his research to Jerry Francesco and Eileen Mielcarek. In the box: Fran Tobin.

Winter 2020

16


Events Highlights Women & Science Program W E D N E S DAY, N OV E M B E R 2 0

WHYY’s Maiken Scott hosted a fireside chat with Dr. Kathrin Jansen, Pfizer senior vice president and head of Vaccine Research and Development, and Dr. Iona Munjal, Pfizer director of Clinical Research and Development, on the extraordinary clinical impact of the HPV vaccine in preventing cancer. ■

Clockwise from top: Dr. Kara Spiller, Seema Kumar, Dr. Alex Helman, Keerthana Gnanapradeepan, Dr. Jennifer Shieh, and Dr. Rocio Isabel Diaz de la Garza; Drs. Kara Coleman and Catherine Grimes; Mary Anne Mennite, Dr. Margaret Foti and Christine Rullo.

Champion Run for Research S U N DAY, N OV E M B E R 1 7

On a brisk November morning, Wistar scientists and staff members ran the annual 2-mile fun run/walk from the Institute to the Philadelphia Museum of Art to raise funds in support of the Institute’s Trainee Association. This year’s run raised more than $6,000 and is the highest-grossing fundraiser the trainees have hosted. ■

A group of participants at the end of the 2019 Run.


Team Elbo & Team Patio Melanoma Walk S U N DAY, O C TO B E R 6

Organizers Eleanor Armstrong and Patrick Dean, along with a close-knit group of friends and family, gathered to participate in the 4th annual Team Elbo & Team Patio Melanoma Walk that raised over $14,000 in support of melanoma research at Wistar. â–

Patrick Dean and Eleanor Armstrong.

AIDS Walk Philly S U N DAY, O C TO B E R 2 0

The Montaner and Abdel-Mohsen labs, on the front line of HIV research at Wistar, participated in AIDS Walk Philly along with thousands of Philadelphia citizens to raise awareness, promote education and combat stigma. â–

Drs. Luis J. Montaner and Mohamed Abdel-Mohsen with members of their labs at the Walk.


PRE-SORTED FIRST CLASS US. POSTAGE

PA I D

3601 SPRUCE STREET PHILADELPHIA, PA 19104-4265

PERMIT #3211

PHILADELPHIA, PA

WISTAR.ORG FOLLOW US ON TWITTER @TheWistar LIKE US ON FACEBOOK Search “The Wistar Institute” CONNECT WITH US ON LINKEDIN Search “The Wistar Institute”

How do you leave a legacy? Include Wistar in your estate plan and make a lasting investment in the promising future of biomedical research. LEARN MORE:

EDITORIAL STAFF

Darien Sutton, Media Relations & Communications Manager Silvia Licciulli, Ph.D., Science Writer Markisha Evans, Digital Marketing Specialist DESIGN BY WFGD STUDIO.

wistar.plannedgiving.org Focus on The Wistar Institute is published for donors, friends, faculty, and staff of the Institute. To contact the editor, call 215-898-3826 or email comm-marketing@wistar.org. Email development@wistar.org for address changes.

Women & Science Program PUSHING THE ENVELOPE IN CANCER IMMUNOTHERAPY THURSDAY, FEBRUARY 20, 2020 6 TO 8 P.M.

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

© 2020, THE WISTAR INSTITUTE

wistar.org/womenandscience

The Wistar Institute is a National Cancer Institute-designated Cancer Center.

Profile for The Wistar Institute

The Wistar Institute Focus - Winter 2019 - 2020  

The Wistar Institute Focus - Winter 2019 - 2020