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Expanding Learning Opportunities for Diverse Scientists

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

Dr. Sandra Deliard of the Gardini lab is combining genetics and cell biology to better understand cancer. Born in New York City and raised in Philadelphia, Deliard earned her bachelor’s degree in Biology from the University of Pennsylvania and completed her Ph.D. in Biomedical Sciences with a concentration in Cancer Biology and Genetics at Temple University. She is currently studying epigenetic modifications of myeloid cells – specialized cells in the bone marrow.

In a conversation with Dr. Deliard, she discusses her professional journey, research challenges, and the importance of investing in diverse and underrepresented populations when supporting scientific talent.

Did you come from a family of scientists? Who inspired you growing up to pursue science?

I did not come from a family of scientists, but I have several family members in the medical field. I was always drawn to science growing up, and I wanted to pursue a career in medicine. I began doing research in high school mostly in genetics. Once in college, I continued to work in research labs, which I found more enjoyable than working in a clinical setting. I then decided to pursue science as a researcher because I could still contribute significantly to the advancement of medicine without working directly with patients.

What drew you to Wistar and what do you like about working here?

Following my Ph.D., I wanted to progress in the field of epigenetics and bioinformatics. A colleague in my Ph.D. lab connected me with Dr. Alessandro Gardini, who offered me an opportunity to continue my training as a Postdoctoral Fellow in his lab. Wistar is a highly regarded Institute and well known for its groundbreaking research. This reputation made it easy to choose to work here. I like the collaborative environment Wistar fosters within the Institute and with other academic institutions in the area, like the University of Pennsylvania. These collaborations allow access to more ideas and technologies that enhance the productivity of the research done in Wistar labs.

What is your favorite part of your role and your day?

I enjoy doing experiments at the bench, but my favorite part is getting results back from sequencing experiments and analyzing the data.

Do you have a challenging moment in your career so far and how did you overcome it?

My most challenging times were during my Ph.D. There were points where it felt like none of my experiments were working, which was stressful because I knew graduation was contingent on me having enough data to write a manuscript for publication. I overcame this by finally reaching out and getting extra help from my mentor and other lab colleagues. Through the years, I also learned to step back and look at the collection of my work rather than focus on a particularly difficult time. This gave me the encouragement to persevere and complete my Ph.D.

What advice do you have for someone who wants to pursue science?

Science is a rewarding career, but there will be difficult and discouraging times. It is crucial to know when to ask for help, whether it is with an experiment or career advice. Also, it is good to have career goals, but you do not have to follow a rigid path. It is okay to change your mind about what you want or don’t want to do. The great thing about science is that there are many paths one can take in various fields, so it is best to stay flexible and keep an open mind about opportunities that may come your way.

Congratulations on receiving the Wistar Diversity, Equity, and Inclusion Travel award. What does this opportunity mean for you?

Thank you! With this award, I can focus more on the bioinformatics training I need to advance my career. More importantly, as a Black woman in science, this award is especially meaningful since there are so few of us in the field. A career in science can be highly competitive. It is even more challenging for people of color, LGBTQIA+ people, and people from under resourced communities, as opportunities for these groups are particularly scarce. I hope Wistar continues to offer opportunities like this and uplift people from underrepresented populations like myself. An equitable representation of different people in the field will only promote better science and more advancements.

The Lab of the Future: AI’s Impact on Biomedical Research

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

The evolution of machine learning and artificial intelligence is changing the way the contemporary lab looks and functions. Researchers today are discovering that breakthroughs can happen not only at the bench, but on the desktop.

Noam Auslander, Ph.D., assistant professor in the Molecular & Cellular Oncogenesis Program of Wistar’s Ellen and Ronald Caplan Cancer Center, conducts her research at the intersection of computer science and biomedical science. The interdisciplinary nature of Wistar provides fertile ground for her innovative lab to flourish and tackle research questions from a multifaceted and collaborative perspective. She uses advanced techniques to investigate genetic factors underpinning cancer evolution and viruses to improve diagnostics and therapeutics. As a computational scientist, Auslander applies the power of advanced computational platforms – artificial intelligence (AI) and machine learning (ML) software – to very intricate and complex biomedical data.

Wistar had a conversation with Auslander to find out more about how computer science impacts biomedical research on cancer and viral diseases and the evolution of the next generation research lab.

Can you define artificial intelligence and machine learning?

These are fields in computer science that involve algorithms allowing learning from a set of examples. This can be for instance, learning to make decisions based on data, or to transform one data into another form.

What is unique about using computer science and AI approaches in biomedical research? How far along is the field in biomedical science?

There are some biomedicine areas where AI approaches are very advanced, such as for prediction of protein structure or radiology. However, in other domains, such as for drug identification or precision medicine, it is still in its infancy. Some reasons for these differences are (1) how much data is available to build AI models (2) how much effort is invested to address a particular research question and (3) how well defined the problem is in terms of data and goals.

Why is using advanced computational methods important to biomedical research? What types of knowledge and data can be gathered and analyzed using AI?

We have a huge amount of data that is available to us, and datasets are being generated every day. Within these, there is hidden information that can benefit biomedicine if uncovered, and the only way to do this realistically is by applying computational approaches and improving methodologies that can harness these datasets.

What do you anticipate for the future of computer science techniques in a research space? What does innovation look like in your field?

We need advancements in algorithms and implementations that will make the most use of continuous improvements in computing power.

Just as libraries have dramatically changed with the proliferation of computers and tablets – do you see the lab of the future morphing more into computers and software and fewer test tubes and high-end imaging equipment?

It is already happening – almost every graduate program today is teaching some basic coding skills, and many wet-lab biologists today hire computational staff. This trend will probably continue.

What is one thing you wish people knew about harnessing the power of artificial intelligence for research?

I wish people would be careful and acquire appropriate training before using such tools in their research.

What impact do you hope your work will have on cancer and infectious disease?

We are searching for unknown organisms that are associated with cancers and other diseases. I hope that we will find viruses and bacteria that play a role in these diseases and have not been discovered previously.

How is your day-to-day schedule structured?

I oversee the projects in my lab and some ongoing projects with collaborators. There is a lot of processing data and making sure things are done and defined correctly. For scientific literature, I need to keep track of many fields, including cancer research, viruses and infectious diseases, and new computational advancements ¬– and that’s not easy.

What is your favorite part of work and Wistar?

The best part in work is when we find something that no one found before. Wistar is great because people here are very supportive and collaborative, which allows us to move forward, validate new findings, and apply our methods to other domains.

Do you collaborate a lot and how does your lab work together with other Wistar labs?

We are very collaborative, and we have different types of collaborations. Trainees in my lab decide if they work on collaborative projects and to what extent, and this motivates the ‘how’ my lab works with others.

What advice do you have for those interested in pursuing a career like yours?

Start coding early in life and find programs that allow comprehensive training in computer science and biology.

A Good Cup of Coffee Kickstarts This Researcher’s Day

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

From southeast China, Dr. Xue Hao, a postdoctoral research fellow in the Rugang Zhang lab at The Wistar Institute, is tackling ovarian cancer. With a degree in Applied Chemistry from Nanjing Agriculture University and a Ph.D. in Zoology from the Kunming Institute of Zoology, Chinese Academy of Sciences, Hao brings a unique perspective to Wistar science. She is currently focused on ovarian cancer relapse after chemotherapy by targeting a process called cellular senescence – biological aging of cells and subsequent loss of cell function.

In a conversation with Dr. Hao, Wistar discussed the journey to her current role at the Institute, being a researcher from another country, and where her research will take her.

Did you come from a family of scientists? Who inspired you growing up to pursue science?

None of my family members are scientists. When I was in college, I watched the movie ‘A Beautiful Mind’, a biographical film inspired by the American mathematician John Nash. John was an enthusiastic scientist who struggled with schizophrenia. However, he worked hard and made tremendous contributions to game theory. In 1994, John Nash was awarded the Nobel Memorial Prize in Economic Sciences. I was deeply touched by the last scene in the film where many scientists placed their pens on John’s table to show their highest respect for him. His passion for science inspired me a lot and I hope that someday my work can inspire others and contribute to scientific development.

What drew you to Wistar and what do you like about working here?

When I decided to continue with postdoctoral training, I was very interested in the aging and cancer research field, as global aging is an increasingly serious problem. This field is undergoing robust development and has fundamental clinical implications. Professor Rugang Zhang’s lab met my interests because it is focused on both cellular senescence and epigenetic regulation of ovarian cancer. The lab had so many beautifully rigorous papers published, so I eagerly wanted to join the team.

Also, I had several previous colleagues who worked at Wistar. Their positive comments about the Institute also drew me here. I receive high-quality training that enables me to be competitive across academia. I’ve been here for three years, and I’m very glad that I made a great decision to come to Wistar.

Are there any differences or unique experiences you’ve had working in science in the U.S. compared to China?

There is a major difference with time management. When I worked in China years ago, we usually had a longer lunch time. Many people took a nap after lunch and started to work again at around 13:30 p.m. and then went back home later than I see in the U.S.

What is your favorite part of your role and your day?

As an early bird in the morning, I usually list a daily plan while enjoying coffee. A great cup of coffee can lighten my whole day’s work!

Do you have a challenging moment in your career so far and how did you overcome it?

There have been many challenging moments in my career. I don’t have an epigenetics background, so in the very beginning, I found it hard to move forward with my project both conceptually and technically. I just needed to get the ball rolling. I am lucky that my mentor and lab members are always ready to help. I learned a lot from them, and everything became better.

What advice do you have for someone who wants to pursue science?

There are no shortcuts to learning. Intellectual curiosity is the most important thing on the road to pursuing science. The rest is a matter of practice by reading, writing, speaking your mind, and doing experiments.

Congratulations on receiving the Wistar Diversity, Equity, and Inclusion Travel award! What does this opportunity mean for you?

Thank you! I’m very happy and truly honored. I am quite encouraged and more confident about the direction of my work after receiving this Travel Award from Wistar. It supports my trip to the American Association for Cancer Research (AACR) special meeting where I’m invited to give a talk about my current work. I will take this opportunity as a great kickstart to my next journey in academia. Again, I sincerely thank Wistar for this award!

The Wistar Institute Ranks 3rd in Innovation in New Heartland Forward Report

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

Think tank Heartland Forward released a new report tracking technology transfers from research institutions that lead to innovations that build stronger economies and The Wistar Institute ranked 3rd in Innovation.

The report From Research to Renewal, Part 2: States Realizing the Potential of Research Institutions reviewed 5 metrics related to technology transfer and Wistar ranked 91.14 out of a perfect score of 100. Formal technology transfer metrics considered included licenses and options issues, gross licensing income, invention disclosures, startups formed, and unique citing patents. The report substantiates that strategic investment in scientific and technological innovation, synergy across research institutions, and efficient technology transfer practices build stronger state economies.

Wistar, the nation‘s oldest, private, nonprofit research organization, stays laser focused on biomedical research that improves the quality of life and saves lives throughout the world. Wistar scientists have led the way on some of the world’s most important biomedical breakthroughs, treatments, and vaccines – including for rabies, rubella, and rotavirus. Wistar scientists are advancing a deeper understanding of cancer to develop targeted immunotherapies and investigating innovative immunization solutions for infectious diseases. With 35 laboratories and 289 scientists, students, post docs and staff representing more than 20 countries, Wistar scientist tackle some of the most important health challenges of the 21st century. Wistar science – today’s discoveries, tomorrow’s cures.

Read more in the Philadelphia Business Journal.

The Wistar Institute One of Nation’s Top 3 Research Institutions for Innovation

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

PHILADELPHIA — (OCTOBER 24, 2022) — The Wistar Institute, a leader in biomedical breakthroughs headquartered in Philadelphia, is one of the nation’s top drivers of innovation, research, and tech transfer toward a stronger economy, according to the recently released Research to Renewal report by Heartland Forward., an institute for economic renewal.

Wistar ranks third in the nation in the October 2022 report From Research to Renewal, Part 2: States Realizing the Potential of Research Institutions, which tracks technology transfers from both state university systems and research institutions.

“Wistar’s singular focus on innovative research to tackle some of the most destructive diseases and viruses has yielded incredible advances and continues tradition of collaboration and discovery across generations of scientists,” said Dario C. Altieri, M.D., Wistar president and chief executive officer. “A culture that fosters collaboration is key to Wistar’s success as a discovery engine.”

Wistar ranked 91.4 out of 100 on the innovation report based on five metrics related to technology transfer, including licenses and options issues, gross licensing income, invention disclosures, startups formed and unique citing patents. The findings substantiate that strategic investment in scientific and technological innovation, synergy across research institutions and efficient technology transfer practices are key in building stronger economies.

Innovation, synergy and tech transfer “too important to go unmeasured”

According to the report, strategic investment in scientific and technological innovation, synergy across research institutions and efficient technology transfer practices are key in building stronger economies. Technology transfers – or sharing the results of research that leads to innovation – are considered an important component of a state’s innovative ecosystem. Private research institutions, such as Wistar, are often cited in patent filings, are valuable sources of new inventions with commercial potential, are considered regional assets that contribute to research transfer.

Founded in 1892 as the first independent nonprofit biomedical research institute in the country, the Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine and immunotherapy development. Wistar’s nearly 300 scientists in 35 labs representing 20 countries have led the way on some of the world’s most important biomedical breakthroughs, treatments, and vaccines – including vaccines for rabies, rubella, and rotavirus.

“The ability of American universities and research institutes to transfer technology to the commercial sphere is simply too important to go unmeasured,” the report authors note. “No matter how much money is spent on research and development, society will not benefit unless there are tangible outcomes. The American system of innovation is predicated on partnerships between research institutions and industry to maintain an internally competitive edge.”

The report’s authors recommend several key opportunities based on findings, including:

  • Renewing the promise of innovation-driven economic growth in the United States through investments in scientific and technological innovation; and
  • Strategically investing in and deploying resources to create entrepreneurial ecosystems aimed at commercializing the results of scientific research through technology transfer.

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The Wistar Institute, wistar.org, the first independent, nonprofit, private, biomedical research institution in the U.S. marshals the talents of an international team of outstanding scientists through a highly enabled culture of biomedical collaboration and innovation, to solve some of the world’s most challenging and important problems in the field of cancer, immunology, and infectious diseases, and produce groundbreaking advances in world health. Consistent with a pioneering legacy of leadership in not-for-profit biomedical research and a track record of life-saving contributions in immunology and cell biology, Wistar scientists pursue new and courageous research paths to life science discovery, and to accelerate the impact of early-stage discoveries by shortening the path from bench to bedside.

Heartland Forward is a non-partisan, non-profit think-and-do-tank focused on improving economic performance in the center of the United States. It’s research institutions category includes hospitals, private research institutions and government-owned contractor-operated labs, plus government-owned and government-operated labs. See the full list here.

Dr. Maureen Murphy examines data with her students.

Dr. Maureen Murphy: Scientist and Teacher

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

Wistar offers the perfect blend of qualities for cancer researchers to thrive.

Challenging science paired with a social cause is the winning formula that propels Dr. Maureen Murphy in her quest to cure cancer. A researcher for over 25 years, Murphy leads research projects on the genetics of the tumor suppressor protein p53 with the goal of improving and personalizing cancer therapies for understudied populations who often have the highest cancer burden, particularly those of African and Ashkenazi Jewish descent. She also serves as a mentor, actively guiding scientists as they navigate the joys and challenges of scientific research. Grit and kindness, she says, is what she searches for when adding talent to her team.

Murphy and her lab thrive in Wistar’s highly collaborative environment, a space that actively rejects scientific ivory towers and welcomes those with curious minds and innovative imaginations. Wistar science pushes forward the frontiers of research in pursuit of knowledge to combat and eradicate cancer. This National Breast Cancer Awareness Month, we spoke with Dr. Murphy, Ira Brind Professor and program leader of the Molecular & Cellular Oncogenesis Program of the Ellen and Ronald Caplan Cancer Center, on her breast cancer research, mentorship, and motivations to understand – and ultimately cure – the disease.

As a breast cancer researcher, what are some of the most significant accomplishments in managing and treating breast cancer in your opinion? Put another way, why should breast cancer patients feel more hopeful today than – say – 10 years ago?

The five-year survival rate for breast cancer has improved dramatically in the last two to three decades – possibly more than any other cancer. I find three most promising things: first is the development of more sensitive ways to detect breast cancer early (including the new revelations about the difficulty for a standard mammogram to detect cancer in women with dense breasts, like Katie Couric … and like me); second is the power of patient advocacy groups and other organizations whose fundraising really powers the research and the patients; third is the discovery of therapies for breast cancer that are not as toxic to the body as the conventional chemotherapy that used to be standard. This allows for more effective therapy that is tolerated better by the body.

What attracted you to focus on cancer research?

When I was a kid, I realized I had more energy than most people. At a young age, I knew I was going to have to choose a career where I could apply all my energy – and as Austrian poet Rilke says, “scrape the bottom of my soul”– at the problem. I could not have chosen a more worthy or more fulfilling cause. I think what most people don’t realize is that, as a scientist, you are not just performing experiments. You are teaching. You are giving young people opportunities. You are always mentoring and caring for people and making the world a better place with your efforts. Can you imagine a better thing to which to devote your life?

As a scientist, what drew you to be a Wistar researcher?

I realized that the most important thing about the place I worked at was the leader – the President/CEO. This had to be someone with three things: good leadership skills – someone able to get people to work together; someone with vision ¬– what aspects were going to be critical for the success of the cancer center; and finally, great science from the leader’s laboratory itself – science that impressed and even daunted me. I found this trifecta exceedingly rare. Most cancer center directors had one while some had two. Exceedingly few had all three. I held out for a job where the leader had all three, and I’ve been thrilled to be here every single day.

What role do your posts docs and students play in advancing treatments and/or a cure?

They have the most important role! They are on the ‘front lines’ of the battle, coming up with questions and new hypotheses to test. Can we screen for chemotherapeutic drugs that kill tumors with particular genetic mutations? Can we screen for drugs that improve the efficacy of immune methods to kill cancer?

My job is to teach them how to ask that question in the best way, whether it be the simplest way, sometimes the most informative way, and often, the most cost-saving way. People do not understand how much money it takes to do all the research to move drugs into the clinic, so cost-effectiveness means you get more information out of your research dollars. Sometimes, I hear postdocs and students asking each other how they would answer a particular science question. Then, I hear one of my trainees say, “Yes that’s a good experiment, but do you realize how much it would cost?” and I smile.

Good job, Grasshopper.

Any advice for others interested in a career in cancer research?

My advice is to get into a lab as soon as you can. Do a one-day visit to a lab. Then work in a lab over spring break. Then work in a lab over the summer in a paid internship. The more research you do, the more you will fall in love with it. Imagine a job where you get to figure out how nature works, what God is thinking, and at the same time know that your work will one day benefit the lives of others. I can’t imagine anything better.

Learn more about Wistar’s Postdoctoral Training Program.

“The London Patient” Adam Castillejo Speaks at William Way Community Center to Spread Hope for a Future HIV Cure

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

PHILADELPHIA—(October 20, 2022)— William Way Community Center, Philadelphia FIGHT, BEAT-HIV Delaney Collaboratory, Philadelphia Foundation, The Penn Center for AIDS Research, and The Wistar Institute are proud to announce that “The London Patient” Adam Castillejo will take part in a reception, followed by a panel conversation and Q&A on Wednesday, October 26 from 5:00 to 8:00 p.m. at the William Way Community Center.

Castillejo is the second person known to be cured of HIV when his body became resistant to HIV infection after receiving a bone marrow transplant. In his case the transplant was to treat Hodgkin’s lymphoma. Timothy Ray Brown, known as the “Berlin Patient”, was the first person cured of HIV with a stem cell transplant, similar to Castillejo. Brown died in 2020 from a recurrence of cancer, and Castillejo revealed his identity that year so he could be an “Ambassador of Hope” to inspire others living with HIV.

Castillejo is a British-Venezuelan man who has resided in London since 2000. In 2003, he was diagnosed with HIV. From that point forward he chose a life of health—exercising, eating well, and becoming a head chef. In 2011, he was diagnosed with Stage 4 lymphoma. After intense monitoring, many ups and downs in treatments, and much intensive preparation, Castillejo received the stem cell transplant that cured him of HIV in London in 2016. After this treatment, his body became resistant to HIV infection, and he subsequently stopped HIV medication in 2017. Since 2020, he has been an international champion of HIV research. His presentation in Philadelphia is the last stop on his international tour before returning to his home in London, United Kingdom.

“Over 30 years ago when the AIDS pandemic started, many of us thought we wouldn’t live to see this day— hearing from a cured person. But here we are.” said William B. Carter, BEAT-HIV Delaney Collaboratory Community Advisory Board Chairperson. “Sharing Mr. Castillejo’s story shows the importance of researchers working together with the community to develop a cure.”

“Adam is a pillar of strength and inspiration and stands as a testament to what HIV cure research can do. In sharing his story, he is amplifying attention to this critical need in biomedicine as well as emphasizing the impact science can have,” said Luis J. Montaner, D.V.M., D.Phil., Herbert Kean, M.D., Family Professor, leader of the HIV Research Program at The Wistar Institute, and co-principal investigator of the BEAT-HIV Delaney Collaboratory. “Adam represents and advocates for what we are all working towards, a cure for HIV within our lifetime.”

To register for event: https://redcap.med.upenn.edu/surveys/?s=FXW4TWKFRLJAKXLK

Editor’s Note: For more information or to cover the event, contact Darien Sutton at 215-870-2048 or dsutton@wistar.org.

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The Wistar Institute, the first independent nonprofit biomedical research institute in the United States, marshals the talents of an international team of outstanding scientists through a highly-enabled culture of biomedical collaboration and innovation, to solve some of the world’s most challenging and important problems in the field of cancer, immunology, and infectious diseases, and produce groundbreaking advances in world health. Consistent with a pioneering legacy of leadership in not-for-profit biomedical research and a track record of life-saving contributions in immunology and cell biology, Wistar scientists pursue novel and courageous research paths to life science discovery, and to accelerate the impact of early-stage discoveries by shortening the path from bench to bedside. Wistar.org

BEAT-HIV Delaney Collaboratory is part of an international consortium of more than 80 top HIV researchers from academia, industry, government, and nonprofit sectors working toward an HIV cure. The Collaboratory is leading three advanced trials to define effective ways to combine immunotherapy regimes towards a cure. BEAT-HIV.org

Philadelphia FIGHT is a Federally Qualified Health Center (FQHC) offering HIV treatment and primary care to people living with HIV/AIDS and those at high risk, as well as community education and outreach programs on HIV, Hepatitis, and other topics impacting public health. During the COVID-19 pandemic, FIGHT has provided no barrier, walk-up COVID testing to over 13,000 people in low income neighborhoods of Philadelphia, and partnered with ten community based organizations to bring COVID vaccines to these communities. fight.org

Philadelphia Foundation, founded in 1918, strengthens the economic, social and civic vitality of Greater Philadelphia. It grows effective philanthropic investment, connects individuals and institutions across sectors and geography, and advances civic initiatives through partnerships and collaboration. A publicly supported foundation, the Philadelphia Foundation manages more than 1,000 charitable funds established by its donors and makes over 1,000 grants and scholarship awards each year. To learn more visit www.philafound.org.

William Way Community Center seeks to engage and support the diverse LGBTQIA+ communities in the greater Philadelphia area through arts & culture, empowerment, and community connections. The Center wants all LGBTQIA+ people to feel safe, connected, and empowered. We strive to be a community center whose staff, management, and board reflect the vibrant and richly diverse communities we serve. In these challenging times, the William Way LGBT Community Center, and what it represents, has evolved to meet the needs of the diverse people it serves.

The Penn Center for AIDS Research (Penn CFAR) is one of 18 NIH-funded CFARs and includes HIV and AIDS investigators at the University of Pennsylvania, the Children’s Hospital of Philadelphia (CHOP), and the Wistar Institute. The mission is to support and advance research in all areas of HIV/AIDS on the Penn/CHOP/Wistar campus through campus, regional and national leadership; catalyzing collaborative research through working groups, outreach and strategic planning; education through seminars, courses and workshops; developing new HIV/AIDS investigators and research programs through pilot funding, mentorship, and partnership programs; and research support through innovative shared resource Cores that offer unique services, materials, technical education and assistance, and collaborative support.

Dr. Kristy Shuda McGuire pipetting with R.W. Brown Boys & Girls Club members.

STEM Night at R.W. Brown Boys and Girls Club: Exploring Our Roots with DNA

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

Dr. Jason Diaz, The Wistar Institute education program director, moved around R.W. Brown Community Center classroom full of aquariums with turtles and fish, assorted plants, and books. Dr. Diaz’s excitement was obvious as he peppered the high school students with questions on what they knew about ancestry tests and DNA—the subject for tonight.

Guided by Dr. Diaz, high school students conducted interactive science experiments revealing genetic ancestry and roused their scientific curiosity. Students practiced lab skills like pipetting, gel electrophoresis (“pushing” DNA through a gel with electricity), and learned to analyze gel results. Dr. Diaz explained DNA and how it’s passed on from parents to children, then plunged into the steps of their experiements.

This after school science class about Exploring Our Roots with DNA was a collaboration amongst a nonprofit coalition including Give and Go Athletics, Caring People Alliance, Lower North Philadelphia Community Development Corporation, and The Wistar Institute. Hosted by the R.W. Brown Boys and Girls Club, a space for children offering sports and arts programming, a pool, a small animal zoo, and career development activities.

The community science event for neighborhood students, the second in the series, aimed to build a foundation of STEM experiences, and bolster exposure to science-related careers and foster a lifelong interest in science.

Science jobs in our life science region are expanding. Events like this expose students to STEM opportunities that can positively impact their lives, the region, and beyond. It encourages students to consider science as a possible career. To be fully immersed in biomedical research, they can participate in our Summer High School Program in Biomedical Research** meant to inspire them to identify as scientists.

Side bar:
For more than 20 years, Wistar was most known for its education, training and apprenticeships exposing nontraditional undergraduate students from diverse backgrounds to biomedical research training opportunities. These opportunities lead students to new careers, further degrees, growth, and mobility. Wistar’s approach to education and training is broad. In the last few years, while wrangling with a pandemic, Wistar’s Dr. Kristy Shuda McGuire, dean of Biomedical Studies, has turbo-charged Wistar’s education and training programs—accelerating and expanding them to more students – from Cheyney University of Pennsylvania, America’s first Historically Black College and University, to more regional community colleges.

Wistar’s educational aspirations run the gamut ¬– training high school students, undergraduates, graduates, and postdoctoral fellows. Wistar also welcomes trainees going back to school as well as adult workers from nonscience fields. Check out this Inquirer story on our newest education and training program with the West Philadelphia Skills Initiative and collaborators. The program is geared to training workers for sought after, much needed life science laboratory jobs in the region.

**Applications for the Summer 2023 High School Program in Biomedical Research will be available this January.

(left) Wistar CEO Dr. Dario Altieri and (right) Dr. Andrew Kossenkov

Wistar Scientists Identify Link Between Mitochondria and Pancreatic Cancer Risk

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

PHILADELPHIA — (OCTOBER 12, 2022) — The mitochondria is a key energy-producing component of the human cell that plays an important role in cancer cell metabolism. In a research paper published in PLOS ONE, Dario C. Altieri, M.D., president and chief executive officer, director of the Ellen and Ronald Caplan Cancer Center, and the Robert and Penny Fox Distinguished Professor at The Wistar Institute, alongside national and international collaborators, distinguish a specific gene signature indicative of mitochondrial reprogramming in tumors that correlates with poor patient outcome.

“To the best of our knowledge, this is the first time that a gene signature of mitochondrial dysfunction is linked to aggressive cancer subtypes, treatment resistance and, unfortunately low patient survival rates. Although our work has focused on the mitochondrial protein Mic60 in this response, we know that dysfunctional mitochondria are commonly generated during tumor growth, suggesting that this is a general trait in cancer,” says Altieri.

This paper stemmed from past research investigating the role of the protein Mic60 in tumor cell proliferation, motility, and metastases. Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT), is a key protein that is essential to the structure of mitochondria and thus has a downstream impact on mitochondrial functions and tumor metabolism.

Andrew Kossenkov, Ph.D., first author on the paper, assistant professor in Wistar’s Gene Expression and Regulation program and scientific director of the Institute’s Bioinformatics Facility, shares, “After original findings on the strong association of Mic60 in low levels in cancer tissues, we were curious if we could identify a small panel of Mic60 downstream genes of specific functions and if the Mic60-low gene panel signature has clinical relevance – i.e., if it is associated with clinical data like survival, cancer sub-types, response to treatment, etc. – and we did.”

Armed with this knowledge, the team – along with collaborators from Canada, Italy, and across the United States – analyzed tumor cells from three independent patient cohorts with pancreatic ductal adenocarcinoma (PDAC). They showed that an 11-gene Mic60-low signature is associated with aggressive disease, local inflammation, treatment failure, and shortened survival – ultimately demonstrating the clinical relevance of protein. Therefore, the Mic60-low gene signature may be used as a simple tool or biomarker to estimate cancer risk for PDAC and potentially other types of cancer, including glioblastoma.

“Gene signatures can be used to gain insight into specific tumor qualities,” Kossenkov explains. “If extensively developed, tested, and validated, this [Mic60-low gene signature] can be a potential simple point-of-service molecular tool for pancreatic cancer prognosis or stratification of patient risks and prediction of treatment response.”

“While the broad applicability of this new Mic60-low gene signature certainly awaits further confirmation in larger patient populations, we hope that this simple, easily implementable molecular tool will be of help in the clinic to stratify patients at higher risk of severe and progressive disease,” Altieri details.

Regarding future directions, Kossenkov suggests that studying broader datasets with extensive clinical information not limited to pancreatic cancer, but also other malignancies can help demonstrate the applicability of the 11gene Mic60-low signature in estimating cancer risks.

Co-authors: Andrew V. Kossenkov, Andrew Milcarek, Jagadish C. Ghosh, Michela Perego from The Wistar Institute; Faiyaz Notta, Gun-Ho Jang, Julie M. Wilson from Ontario Institute for Cancer Research; Steven Gallinger from University Health Network Toronto and Mount Sinai Hospital; Daniel Cui Zhou, Li Ding from Washington University in St. Louis; Annamaria Morotti, Marco Locatelli, Valentina Vaira from Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and University of Milan; Marie E. Robert from Yale University.

Work supported by: This work was supported by National Institutes of Health (NIH) grants P01 CA140043 and R35 CA220446 (D.C.A.) and R50 CA211199 (A.V.K.). The COMPASS study was conducted with the support of the Ontario Institute through funding provided by the Government of Ontario.

Publication Information: Mitochondrial Fitness and Cancer Risk. PLOS ONE, 2022. Online publication.

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The Wistar Institute marshals the talents of an international team of outstanding scientists through a highly enabled culture of biomedical collaboration and innovation, to solve some of the world’s most challenging and important problems in the field of cancer, immunology, and infectious diseases, and produce groundbreaking advances in world health. Consistent with a pioneering legacy of leadership in not-for-profit biomedical research and a track record of life-saving contributions in immunology and cell biology, Wistar scientists pursue novel and courageous research paths to life science discovery, and to accelerate the impact of early-stage discoveries by shortening the path from bench to bedside.

Up in (Antibody) Arms: Synthetic DNA Immunotherapy Platform Combats Brain Cancer

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

Researchers in the Weiner Lab developed DNA-launched bispecific T cell engagers that controlled tumor growth and improved survival in glioblastoma.

Glioblastoma is one of the most severe and aggressive forms of brain cancer with limited treatment options and low survival rates. Wistar’s Weiner Lab is focused on creating new treatments to improve the patient’s quality of life and increase the opportunity to beat this difficult-to-treat cancer.

What approach is Dr. Weiner and his research team taking to tackle glioblastoma?

Dr. Weiner and his team are focused on dBTE’s – a synthetic DNA antibody platform for developing new T cell-redirecting immunotherapies. These immunotherapies deliver a lethal hit against diverse and difficult to-treat solid tumors.

The Weiner lab used genetic engineering combined with direct in vivo expression to create a novel dBTE which targets an important receptor on the surface of cells that initiate glioblastoma tumors. Approximately 75% of individuals with glioblastoma have a very specific receptor referred to as IL-13Ralpha2. The proof-of-concept study of IL-13Ralpha2 dBTEs on controlling glioblastoma was recently published in Molecular Therapy-Oncolytics.

“Glioblastoma is a severe disease with limited therapeutic options so the creation of novel and potentially more impactful therapeutic options for cancer patients such as the anti-glioblastoma dBTE is a major focus of Wistar’s Vaccine and Immunotherapy Center,” says David Weiner, Ph.D., executive vice president, director of the Vaccine & Immunotherapy Center, and W.W. Smith Charitable Trust Professor in Cancer Research.

Bispecific T cell engagers are synthetic antibodies with two chains or “arms” that can simultaneously bind an antigen expressed on a tumor and an antigen on a T cell and bring them closer together, triggering immune activation to protect the body from disease. “This redirects the activity of the T cell towards the tumor cell, attacking and killing the tumor.” explains Pratik Bhojnagarwala, graduate student in the Weiner lab and first author on the paper.

Challenges with conventional BTE treatments for cancer patients include the need for continuous IV injection over several weeks, costly treatment, and unwanted off-target issues. In this work, the team used synthetic DNA technologies to design, test and identify multiple synthetic DNA BTE forms having the most specific and potent killing activity against different glioblastoma human cancer cell lines.

It is this specific design combined with the dBTE approach that creates a kind of dBTE factory for the patient, enabling the consistent force and effectiveness of the therapy. Using this new anti-glioblastoma dBTE and direct nucleic acid encoded delivery, the researchers were able to more than double half-life of the bispecific antibodies in animal models – resulting in the clearing of tumors in vivo.

Dr. Weiner is also a leader in the development of another antibody based technology called DNA encoded monoclonal antibodies (dMAB) for treating infectious diseases including COVID-19, Zika, Ebola, and cancer. The biggest difference between dMABs and dBTEs is that dMABs encode for monoclonal antibodies that bind to a single target. DBTEs are designed to bind to two different targets at the same time and are more commonly used to engage the immune system to fight cancers. By innovating multiple types of platforms, the Weiner lab is on the forefront of translational studies harnessing basic science to fight difficult human diseases.

Bhojnagarwala plans to continue developing combination novel immunotherapies for cancer and infectious disease, specifically exploring additional designs for dBTE that can improve specificity and potency of the new approach and applying his studies towards targeting more tumor antigens for glioblastoma. He shares, “It is important for me to work in a lab where there is a high possibility that the work can rapidly be translated into clinical trials. The Weiner lab provides that platform.”