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Dr. Maureen Murphy: Scientist and Teacher

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

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.

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

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.

Wistar Scientists Identify Link Between Mitochondria and Pancreatic Cancer Risk

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

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.”

[Virtual] Distinguished Lectures in Cancer Research Series: Target Discovery in the Glioblastoma Tumor Microenvironment

Scientific Seminar
Tuesday, Oct. 11, 2022

The Distinguished Lectures in Cancer Research series is the flagship seminar series of The Wistar Institute Cancer Center and features national and international leaders in basic and translational cancer research. Recent speakers (2020-2021) included Paul Mischel, Mark Yarchoan, Maria Blasco, Job Dekker, Nicholas Proudfoot, Moshe Oren, and Judith Varner, among others.

This virtual seminar will be hosted from 12:00 – 1:00 p.m. and is targeted to graduate and undergraduate students, staff, faculty, and anyone interested in cancer research.

If interested in attending or if you have any questions, please email William Alston at alston@Wistar.org.

Speaker

Francisco J. Quintana, Ph.D.
Brigham and Women’s Hospital at Harvard Medical School
Target Discovery in the Glioblastoma Tumor Microenvironment
Faculty Host: Rahul Shinde, D.V.M., Ph.D.

Join Virtually

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Women & Science Virtual Helen Dean King Award Ceremony: What the Sugar Coating on Your Cells is Trying to Tell You

Special Event
Thursday, Nov. 17, 2022

Join us for our virtual Women and Science event!

Recognizing Outstanding Women In Biomedical Research

HELEN D. KING AWARD VIRTUAL EVENT

Carolyn Bertozzi, Ph.D., 2022 Nobel Prize Laureate in Chemistry, and past recipient of the National Academy of Sciences Award in Chemical Sciences, the MacArthur Foundation Genius Award, and the Wolf Prize in Chemistry, will be honored with The Wistar Institute’s 2022 Helen Dean King award, celebrating outstanding women in biomedical research. Dr. Bertozzi, the Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences at Stanford University, is being recognized for her work on understanding how sugars that coat our cells impact cancer and bacterial infections and for devising drug targets to combat them.

Guest Speaker Bio:

Dr. Carolyn Bertozzi is the Anne T. and Robert M. Bass Professor of Chemistry and Professor of Chemical & Systems Biology and Radiology (by courtesy) at Stanford University, and an Investigator of the Howard Hughes Medical Institute. She completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. In 2022, Dr. Bertozzi, along with colleagues Drs. K. Barry Sharpless and Morten Meldal, were honored with the 2022 Nobel Prize in Chemistry for their discovery and contributions to the field of click chemistry.

Prof. Bertozzi’s research spans the disciplines of chemistry and biology with an emphasis on studies of cell surface glycosylation as it relates to specific diseases. Her lab focuses on profiling changes in cell surface glycosylation associated with cancer, inflammation, and bacterial infection, and leveraging this information to develop diagnostic and therapeutic approaches, most recently in the area of immuno-oncology. She has been recognized with many honors and awards for her research accomplishments. She is an elected member of the Institute of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences. She has been awarded the Lemelson-MIT Prize, the Heinrich Wieland Prize, and a MacArthur Foundation Fellowship, among many others.

The event is free and open to the public.

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Wistar’s Dr. Amelia Escolano Earns NIH Director’s New Innovator Award

PHILADELPHIA — (OCTOBER 4, 2022) — The National Institutes of Health has awarded Amelia Escolano, Ph.D., assistant professor in The Wistar Institute’s Vaccine & Immunotherapy Center, the 2022 NIH Director’s New Innovator Award. The honor provides Escolano with a $1.5 million grant given in two parts over a total of five years. The prestigious New Innovator Award recognizes exceptionally innovative, early career scientists proposing high-impact research with unconventional approaches to major biomedical and behavioral research challenges.

Escolano completed her scientific training in Spain, Finland, and the United States. She was recruited to Wistar in 2021 and has since focused her research on identifying guidelines for the design of vaccines that will induce long term protection against viruses that mutate frequently in humans such as HIV, influenza, and potentially future variants of SARS-CoV2. With the award, Escolano intends to expand her work on designing universal vaccines by assessing novel sequential immunization strategies, developing broadly effective antibodies, and tracking immune cell interactions upon repeated vaccination.

“It is an honor to be recognized for the NIH Director’s New Innovator Award. I am grateful to the NIH and excited that this opportunity will accelerate my work in innovative vaccine design to address some of the world’s most pressing health challenges,” Escolano shares.

As a recipient of the 2022 NIH New Innovator Award, Escolano was also invited to attend the High-Risk, High-Reward Research Symposium in summer of 2023. The NIH makes approximately 100 NIH Director’s awards each year depending on the availability of funds, including the NIH Director’s Pioneer Award, the NIH Director’s Transformative Research Award, the NIH Director’s Early Independence Award and NIH Director’s New Innovator Award. These awards are funded and administered by the Office of the Director and 27 Institutes and Centers across the National Institutes of Health. Escolano was also named a 2022 Pew Scholar this summer in support of her breakthrough research.

Dario C. Altieri, M.D., Wistar president & CEO, director of the Ellen and Ronald Caplan Cancer Center, and the Robert and Penny Fox Distinguished Professor said, “Wistar science is a leading force in developing biomedical solutions of the future, and Amelia’s work is testament to some of our most transformative research projects toward vaccines and immunotherapies. We are extremely proud of her for this prestigious recognition.”

Grant Information: DP2AI175470

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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. wistar.org

Fighting Breast Cancer Disparities Through Collaboration

A decade-long collaboration between Wistar and ChristianaCare is leading to new discoveries and better treatment for triple-negative breast cancer patients.

Dario C. Altieri, M.D., president, CEO, and director of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute, and Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute at ChristianaCare, formed a collaboration between the two institutions that would expedite the pipeline of cancer interventions from bench to bedside.

“We had the patients, and they had the world-class science,” said Petrelli. “We felt that this was a great opportunity between an NCI-designated, basic science research center and an NCI community cancer center. This relationship is unique in cancer research.”

This collaboration has yielded more than a dozen translational cancer research papers to date and advanced research discoveries made in Wistar labs into early clinical trials at ChristianaCare. One of the newest projects to come from this collaboration is a population health study on treating triple-negative breast cancer.

RESEARCHING TRIPLE-NEGATIVE BREAST CANCER

Triple-negative breast cancer is an aggressive form of breast cancer with few treatment options. It’s more than twice as common in Black women as in white women, and Black women have a 40% higher mortality rate [1, 2]. These factors are what led Zachary Schug, Ph.D., an assistant professor in the Molecular and Cellular Oncogenesis Program at Wistar’s Ellen and Ronald Caplan Cancer Center; Jennifer Sims-Mourtada, Ph.D., lead scientist and director of Translational Breast Cancer Research at ChristianaCare’s Helen F. Graham Center & Research Institute; and Scott Siegel, Ph.D., MHCDS, director of population health research at ChristianaCare to join forces.

Siegel says, “Disparities in breast cancer are the result of multiple interacting factors operating at different scales, so if we’re going to do something meaningful, we can’t take a silo-based approach and focus on one key variable. We really do need to look across this spectrum.”

ALCOHOL AND BREAST CANCER

Schug, Sims-Mourtada, and Siegel share three intersecting research interests: breast cancer, health disparities, and investigating the connection between alcohol and cancer – truly the linking factor in the context of this project.

As a molecular and cellular biologist, Schug examines the problem of alcohol and breast cancer at the “smallest” level of the three researchers. His research has shown that breast tumors feed on a breakdown product of alcohol called acetate, which they use to grow and fight the body’s immune responses. How and why the breast cancer cells use acetate in this way are questions Schug continues to pursue. However, it’s important for him to make his work clinically meaningful as quickly as possible.

“Instead of just focusing on individual tumor cells and trying to do things at a
molecular level, we wanted to ask more broad questions,” Schug explains, “and
that’s where Scott and Jen come in with what they’re doing.”

GENETICS AND ALCOHOL METABOLISM

Sims-Mourtada is a translational breast cancer researcher who studies how gene expression regulates and alters the progression of breast cancer. Her work intersects neatly with Schug’s because she is investigating whether race-based differences at the genetic level affect how many alcohol-metabolizing enzymes are produced in breast cancer stem cells.

“We have some data that show that a certain isoform of enzyme is overexpressed in tumors from Black women, and a possible reason for this could be some kind of genetic factor,” said Sims-Mourtada. Specifically, there are reports from alcohol use disorder research suggesting the existence of tiny genetic variations called single nucleotide polymorphisms (SNPs) that may be involved in alcohol metabolism. Sims-Mourtada is working on identifying SNPs that might cause an alcohol-metabolizing gene to become overactive or underactive in individuals of differing races which, combined with the individual’s alcohol use, could increase tumor growth.

ALCOHOL-RELATED ENVIRONMENTS AND BEHAVIORS

Siegel looks at the problem of triple-negative breast cancer at a population level. His research focuses on identifying modifiable risk factors for cancer—i.e., whether people’s cancers can be affected by where they live and what they do.

“My contribution to this project is to collect behavioral data on patients. Then we can relate these variables to the processes Jennifer and Zach are looking at, including the enzymes that metabolize alcohol and ultimately the metabolites,” said Siegel.

In examining prevalence of triple-negative breast cancer within ChristianaCare’s home state of Delaware, he found that the areas that have the highest rates of this cancer also have the highest rates of alcohol use disorder and the highest density of alcohol retail stores. The collaboration will help to dig into the biology and genetics that may belie this correlation.

THE RESEARCH PROJECT

The researchers plan to recruit 1,000 women with breast cancer, 500 Black and 500 white. They will biopsy the women’s tumors, which Sims-Mourtada will use to examine differences in gene expression by race. They will also take blood, which Schug will analyze for levels of ethanol and acetate in order to assess the patient’s drinking level, as well as nutrients to get a sense of the patient’s diet. Finally, the researchers will collect extensive patient reported data – including lifestyle, environmental, and socioeconomic factors – which Siegel will assess to determine how the patient’s behaviors and environment relate to what is happening inside their body.

“I think it’s a unique approach to be looking at this multi-level analysis. We’re not just taking into consideration the neighborhood or the behavior, but how those influence what actually happens biologically and genetically,” said Sims-Mourtada.

IMPACTING PATIENTS, PROVIDERS, AND COMMUNITIES

At a patient level, the researchers are hoping to identify biomarkers that would not only indicate risk of developing triple-negative breast cancer but also help detect the cancer sooner than is currently possible via conventional methods.

“Triple-negative breast cancer may start earlier in life before mammography is recommended or develop between screenings. To be able to do a blood test the way one could do a cholesterol test for heart disease, maybe we can see cancer developing sooner,” said Siegel.

The researchers also want to uncover risk factors that healthcare providers can use to educate patients and steer them toward behaviors that match their individual risk level. Alcohol consumption won’t necessarily increase cancer risk for everyone. But it will for some, and those individuals should be informed. With just gentle nudges from a physician, simple changes in alcohol consumption could save lives by reducing the probability of breast cancer in certain high-risk individuals.

At a community level, identifying where rates of risk for triple-negative cancer are highest could mean more targeted outreach. To be able to use public health resources in the areas where they could make the biggest impact could amplify effects on many lives.

A LASTING COLLABORATION

Wistar and ChristianaCare’s joint efforts have repeatedly yielded a two-way benefit: basic scientists learn directly from clinicians about the issues clinicians are seeing at the bedside, and the clinicians learn from the scientists about the challenges scientists face as they are trying
to solve problems in the quest for therapeutic solutions.

“We will be publishing in basic science journals, but we will also be changing how we practice in the cancer center, potentially how we do our community outreach, and possibly prevent loss of life as a result of this research,” said Siegel.

“It really has been a special marriage made in heaven,” said Petrelli, “and I see it continuing for a long time.”

SOURCES

  1. McCarthy, A. M., Friebel-Klingner, T., Ehsan, S., He, W., Welch, M., Chen, J., Kontos, D., Domchek, S. M., Conant, E. F., Semine, A., Hughes, K., Bardia, A., Lehman, C., & Armstrong, K. (2021). Relationship of established risk factors with breast cancer subtypes. Cancer Medicine, 10(18), 6456–6467. https://doi.org/10.1002/cam4.4158
  2. Cancer of the Breast (Female) – Cancer Stat Facts. Chart Death Rate per 100,000 Persons by Race/Ethnicity: Female Breast Cancer. (2018). SEER. https://seer.cancer.gov/statfacts/html/breast.html

Supporting Science Across Borders with Student Exchange

Nestled in Northern Italy, the city of Bologna is one filled with medieval architecture, sprawling city squares, and a culture of scientific excellence. The University of Bologna is considered the oldest university in the western world and asserts a reputation as a leading institution for biomedical education in Italy and around the globe. In 2020, The Wistar Institute kickstarted a Ph.D. exchange program with the University of Bologna for budding scientists in cell and molecular biology. Exchange students travel to Philadelphia and complete their thesis over the course of three years at the Institute while being supervised by a Wistar principal investigator and immersed in a collaborative, supportive research environment.

Ilan Kirkel, an exchange student in Wistar’s Gardini lab, who presented a research proposal to University of Bologna faculty and was invited to Wistar by Alessandro Gardini, Ph.D., said, “I looked online, and it just seemed like the most unbelievable place with so many opportunities. I thought, ‘Count me in! I’ll see you in November!’.” Ilan is currently researching biological machinery involved in regulating the process of transcription. Specific transcription complex subunits are potentially linked to the repair of DNA breaks, which is an important activity that affects the functioning of cells and Ilan seeks to understand these regulatory processes.

Exchange student Davide Maestri is working in the lab of Italo Tempera, Ph.D., on understanding the mechanism underpinning Epstein-Barr Virus (EBV) latency in hosts. EBV latency could present differently in immunocompetent versus immunocompromised individuals and these differences could be linked to tumor formation, making the latency mechanism a potential effective target to treat EBV-associated tumors. “What attracted me to this exchange program was the possibility of incredible professional growth. I’ve always wanted to expand my “research horizons” to cancer research and genomics and after reading the projects that were ongoing in the Tempera Lab, I thought it would be a perfect match for me,” Davide states.

An exchange student in the lab of Rugang Zhang, Ph.D., Simona Lombardi is focusing on the epigenetics of cancer. “I always dreamt about being a researcher and this program was the perfect opportunity for me to achieve my goal. I remember my joy when I found the lab that could best match me at the Institute,” Simona recalls. Her Ph.D. thesis project is about investigating epigenetic alterations involved in endometrial cancer and revealing potential therapeutic targets for more effective cancer treatments.

Learning in a Creative and Nurturing Environment

Students in The Wistar Institute and University of Bologna Ph.D. Exchange Program in Cell and Molecular Biology have been in Philadelphia kickstarting their science. In addition to settling in and starting their research, these students have been immersed in an innovative atmosphere unique to Wistar that is focused on learning and career building.

“I feel academically liberated,” Ilan divulges. “It’s wonderful to be surrounded by so many driven and intelligent people. At Wistar, you can tackle problems from almost every single angle. For example, I just participated in Wistar’s Life Science Innovation course where we gave a ‘shark tank’ style biotechnology pitch to investors and it exposed me to the business side of life sciences.”

Simona, who joined Wistar in late 2020, affirms, “Day after day, I am more convinced that the choice I made for my Ph.D. program has been the best one. I believe that a Ph.D. is a fundamental step in our growth as researchers, and we must choose it carefully and find a place that nurtures and feeds our passion even more.”

Davide provides a perspective as one of the students who has been at Wistar the longest, adding, “I’ve been here a year and a half now, and this has been one of the best experiences in my life so far! I had the opportunity to work in close contact with highly competent and humble people who are always ready to help me with my experiments.”

A Future of Internationally Reaching, Impactful Science

Looking forward, the exchange students will continue to craft their thesis projects and investigate the endless mysteries that the life sciences field poses to researchers.

Davide intends to pursue a career in academia. He details, “I still have another year and a half in front of me here at Wistar that I hope will be as scientifically stimulating as the first half of my exchange.” After his thesis defense, he would like to remain in the U.S. and start a post-doctoral position. Simona is also planning on staying in the U.S. after finishing this program and pursuing her scientific questions even further. “I am determined to continue my career in the field of cancer research,” she states.

“A Ph.D. crystallizes as time goes on,” says Ilan. “Being at Wistar and seeing cutting edge research and utilizing state-of-the-art resources helped me realize I can do so much.” He feels prepared to quickly move into an academic research position after completing his degree but is staying open to the diverse career opportunities to be pursued in the life sciences. “Three years is a bit of time for me to think and see what else I can accomplish.”

With promising talent and a degree program that addresses the creative, collaborative, and global nature of successful STEM research careers, the Institute is excited to continue supporting these Ph.D. students as they discover, innovate, and impact.