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Dr. Amelia Escolano

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

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

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

Human crowd forming an awareness ribbon symbol above human hands on white background.

Fighting Breast Cancer Disparities Through Collaboration

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

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

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

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.

Finding Balance at the Bench

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

This National Postdoc Appreciation Week, we asked our postdoctoral fellows how they strive to keep balance between their research and personal lives.

Wistar postdoctoral fellows serve as critical members of a principal investigator’s lab. They have the opportunity to lead independent projects, delving deeper into scientific questions beyond their Ph.D. degree. Our postdocs are mentored and trained by leading scientists and involved with cutting edge research to prepare them for lasting careers in biomedical research and the life sciences.

Exercise and Other Hobbies

In Wistar’s Ellen and Ronald Caplan Cancer Center, exercise and creative expression keep some of our postdocs balanced.

Dr. Xue Hao in the lab of Rugang Zhang, Ph.D., is currently working on the interplay between tissue aging and cancer and hopes her research can inform strategies to promote healthy aging and combat cancer.

She shares, “I always try to find some ‘me time’ to balance the intensity of bench work. I am a strong believer in daily exercise and good sleep to help me stay positive and energized. I also enjoy listening to classical music, sketching, and cooking.” Hao also enjoys watching tennis games, inspired by the champion players and their mental fortitude to help her overcome challenges in her life.

Exploring Beyond the Lab

In the Vaccine and Immunotherapy Center of the Institute, some postdocs turn to travel and exploration of the world around them to find their balance.

Dr. Maria Belen Palacio in the lab of Amelia Escolano, Ph.D., develops new models to address challenging immunology questions in vaccine design and infectious diseases. Originally from a small town called Metán in the northwest corner of Argentina, Palacio is the second eldest of four siblings and spent her spare time during her college years visiting her large family. Now 7,000 kilometers away from them, she has taken this time to engage with the new environment in which she now lives.

She explains, “Whenever I feel stressed, my family is my strongest support. I also like running and outdoor activities. Since I am new to the U.S. and to Philly, I really enjoy exploring new areas of the city and traveling to nearby places.”

Blue and green banner for The Wistar Institute's Women & Science Program series with a photo of Dr. Elizabeth Jaffee

Setting a Prime Example: Wistar’s Women & Science Program featuring Dr. Elizabeth Jaffee

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

As attendees tuned into their screens, Dr. Elizabeth Jaffee began her presentation Pancreatic Cancer Is PRIMED to Become an Immunologic Disease. With a full house of Zoomers, the Deputy Director of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins School of Medicine discussed her cutting-edge research to develop immune-based therapies for pancreatic cancer at Wistar’s most recent Women & Science event.

Jaffee’s passion for science began with her inspirational 4th grade math teacher and later in her youth by reading Marie Curie’s biography. The seemingly endless scientific opportunities of the early days of the U.S.’s space race also played a role in her career choice. “I think today is just like when I was growing up – the opportunities in science are endless, particularly in biomedical research with the recent technological revolution. It’s a very exciting time in history.”

During her college years, Jaffee became increasingly focused on vaccines, which led to her current work developing pancreatic cancer treatments. She explains that with a high recurrence rate, increasing mortality, late diagnosis with no specific early symptoms, and high-risk populations, pancreatic cancer is an ideal model for studying immune resistance.

Jaffee developed a vaccine that operates by inserting a gene into tumor cells to express signals that attract the immune system and induce a response from T cells. However, tumors protect themselves from the immune system by inactivating T cell response. Antibodies can be designed to enhance a suppressed T cell response, and thus underpins the second step in Jaffee’s emerging immunotherapy strategy. By first inducing T cell activity with vaccines and then optimizing T cell function with antibodies, Jaffee hopes to intercept and eliminate cancers at the earliest stage before they develop immune resistance.

With the advancement of molecular and sequencing technologies, Jaffee is looking at developing immunotherapies specific to cancer patients. “We are at a time where we can personalize treatments for patients,” she shared.

Dr. Jaffee earned her M.D. from New York Medical College. She is currently a principal investigator at John Hopkins University, chair of President Biden’s Presidential Cancer Advisory Panel, and holds six vaccine patents. The presentation concluded with a Q&A session led by Amelia Escolano, Ph.D. and Jessie Villanueva, Ph.D., the scientific advisors for the Women & Science program.

Learn more about Wistar’s Women & Science Program.

3D rendering of PD-1 and PD-1L protein molecules on t cell and cancer cells binding as part of a immune checkpoint

Wistar Scientists Identify Key Biomarkers that Reliably Predict Response to Immune Checkpoint Inhibitor Therapy for Melanoma

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

New research finds biological processes that improve prediction of therapeutic performance and provide a framework to develop predictors for this aggressive skin cancer.

PHILADELPHIA — (SEPTEMBER 19, 2022) — Immune checkpoint inhibitor (ICI) therapy is a type of treatment for melanoma, the deadliest form of skin cancer, which blocks proteins on tumor or immune cells that prevent the immune system from killing cancer cells. While this treatment has shown some clinical success in patients with advanced stages of melanoma, its efficacy depends on reliable predictors of a patient’s response to the therapy. Currently, the only FDA approved biomarker for ICI melanoma treatment is the tumor mutation burden assay, ¬but the mechanisms linking it to ICI remain unclear. However, new research now provides evidence of novel, reliable biomarkers that predict therapy response using advanced computer technology.

In a paper published in Nature Communications, Noam Auslander, Ph.D., assistant professor in the Molecular & Cellular Oncogenesis Program of Wistar’s Ellen and Ronald Caplan Cancer Center, and Andrew Patterson, graduate student in the Auslander lab, identify novel predictors of ICI therapy for melanoma. In particular, mutations in the processes of leukocyte and T-cell proliferation regulation show potential as biomarkers with reliable and stable prediction of ICI therapy response across multiple different datasets of melanoma patients.

“This work aims to identify better and more biologically interpretable genomic predictors for immunotherapy responses,” notes Auslander. “We need better biomarkers to help select patients that are more likely to respond to ICI therapy and understand what factors can help to enhance responses and increase those numbers.”

Using machine learning and publicly available de-identified clinical data, researchers investigated why some melanoma patients responded to ICI therapy and others did not. Patterson, first author on the paper, details that their research process involved training machine learning models on a dataset to predict whether a patient responds to ICI therapy, and then confirming that the model was able to continually predict response or resistance to this treatment over multiple other datasets.

The team found that leukocyte and T-cell proliferation regulation processes have some mutated genes that contribute to ICI treatment response and resistance. This knowledge could be used to identify targets to enhance responses or mitigate resistance in patients with melanoma.

“We were able to better predict if a patient would respond to ICI therapy than the current clinical standard method as well as extract biological information that could help in further understanding the mechanisms behind ICI therapy response and resistance.” Patterson explains.

The scientists intend to continue this work with the goals of increasing prediction accuracy, further understanding biological mechanisms underpinning patient resistance or responsiveness to ICI therapy, and determining whether the processes distinguished in the paper can also serve as predictors of ICI treatment response for other cancer types.

Co-author: Andrew Patterson

Work supported by: The results shown here are in whole or part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. The research reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under Awards R00 CA252025 and P50 CA174523.

Publication Information: Mutated Processes Predict Immune Checkpoint Inhibitor Therapy Benefit in Metastatic Melanoma. Nature Communications, 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.

Unraveling The Enigmas of Melanoma

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

Meenhard Herlyn, D.V.M., D.Sc., is known internationally as one of the fathers of melanoma research. As the founder of The Wistar Institute Melanoma Research Center, he has led the way with breakthrough discoveries about this mysterious and hard-to-treat cancer. A highlight of his work includes building Wistar’s collection of patient-derived xenografts — a groundbreaking tool that allows tumor cells to be implanted into models for melanoma research.

Now, a new generation of melanoma researchers are building on that foundation. This up-and coming-scientific force includes Chengyu Liang, M.D., Ph.D., a rising star in studying how UV exposure damages cells.

“Dr. Herlyn is a great mentor and a great scientist,” Liang said. “He established the platform, the foundation, that has been indispensable not only for Wistar melanoma research, but for the entire melanoma research field.”

BUILDING A BETTER MODEL

“One of the guiding forces in our research has been to mimic human disease, to figure out what makes cells become cancer, and to use this knowledge for new strategies to develop therapies,” Herlyn said.

One of these strategies involves the use of artificial skin. Lab-grown skin had previously been developed for wound healing. Using this existing technology, Herlyn pioneered its application to melanoma research. Herlyn’s team was the first to use artificial skin to grow and study melanocytes — normal pigment cells — which they have used to understand how cancer cells form and how to make treatment more effective.

“We wanted to really know what tumor cells do, and to understand that, we first need to know what normal cells do and where the tumor cells come from,” he explained.

Herlyn joined Wistar in 1976 and spent the early years of his career focused on developing monoclonal antibody treatments, a breakthrough drug that mimics or enhances the immune system’s natural disease fighting activity to attack cancer cells.

One of Herlyn’s frequent collaborators during this time was his wife, Wistar scientist Dr. Dorothee Herlyn, who is now retired. “She was the immunologist of the family,” he said. Together, they helped develop a number of monoclonal antibody molecules, some of which are still used in cancer therapies today.

Herlyn is also behind Wistar’s patient-derived xenograft program which supports a collection of patient cancer tissues. These samples can be implanted into genetically altered mice to more closely mimic conditions in the human body. It’s a powerful tool scientists can use to conduct cancer experiments and test new treatments under conditions that more closely mimic the disease in humans.

“We now have more than 500 tumors from patients,” Herlyn said. “These come directly from the patient and are implanted without ever being cultured, making them much more like real life tumors.”

THE “SUNSCREEN GENE” AND MELANOMA

Dr. Liang didn’t set out to study melanoma. Originally trained as a medical doctor, she became a research scientist with the mission of improving patient outcomes. Her drive to understand cancer and develop better treatments became more personal after her mother passed away following a two-year battle with cancer.

“When someone you love has cancer, you’re trying to find answers. Why did this person have cancer? Why is this treatment not helping?” she said. “Eventually, that drove me to get my Ph.D. in medical science. I wanted to know more.”

Liang initially focused her research on tumor virology, studying how viruses cause cancer. During her research, she encountered a gene called UVRAG that piqued her interest in melanoma.

Previous work had found that this gene seemed to be involved in protecting skin cells from UV radiation, but the mechanism behind it was unclear. Liang’s team showed how the gene repaired DNA damage from UV radiation, and that disrupting the gene could increase a person’s risk of melanoma and other skin cancers. They nicknamed UVRAG the “sunscreen gene.”

The finding sparked many questions about how UV radiation causes genetic mutations that lead to cancer. “The question we asked is, ‘What makes melanoma melanoma?’” she said.

One thing that sets melanoma apart is its extremely high rate of genetic mutations — much higher than other cancers. “It’s in the skin, which is where the body interconnects with the environment and UV radiation, so in a way, that’s not surprising,” she explained.

Liang’s recent research has focused on identifying signs of DNA-repair deficiency as an early sign of damage that can trigger melanoma-driving mutations. “If we can find genetic signs that can predict this process, we might be able to catch the disease much earlier,” she noted.

CULTURING COLLABORATION

Herlyn not only laid the groundwork for Liang and fellow cancer researchers. He also serves as a leader and mentor who is generous with his knowledge and support, Liang said. “He’s like a big dictionary of melanoma,” she described. “When you have a question, he can always share something instructive.”

This philosophy of collaboration, Herlyn shared, has been a driving force in his work. “One of the major strengths at Wistar has been our flexibility and our ability to look for collaborators,” he pointed out. “My approach has always been to look for the best people I could work with.”

This has included a longtime collaboration with oncologists, pathologists, and other clinical colleagues at the University of Pennsylvania as well as other institutions. “I’ve always believed strongly in a good connection between the laboratory and the clinician,” he said.

Herlyn also helped found the Society for Melanoma Research, the first ever medical conference dedicated to bringing together researchers, clinicians, and patients to share knowledge about melanoma. Liang emphasized that with such a complex and unique disease, it’s critical for scientists to work together to find new diagnostic tools and treatments.

“There’s still a lot of mystery,” she stated. “Despite all the tremendous progress we have made in the melanoma field, I think we are still at the tip of the iceberg.”

Career Spotlight: Carlos Carmona in the Montaner Lab

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

Recently, The Wistar Institute created a virtual tour of our Montaner Lab which focuses on infectious disease research such as HIV through highly collaborative regional and international projects. We interviewed Carlos Carmona, Data and System Manager for the team. Read more about how he got to where he is now, and a glimpse inside working in the Montaner Lab at Wistar.

What is your personal story, journey to science, and future goals?

My career story is not as clear cut as some may expect. In college, I studied public health, where I wanted to understand and promote the health and well-being of all people. From mapping out how diseases spread to launching initiatives that keep communities healthy, public health touches almost everything you can imagine. As a first-generation Latino college graduate from North Philly, it was quite daunting trying to navigate my options and find a place where I can make an impact in my city.

Then, I stumbled upon data. Before working at Wistar, I had been in research projects that always asked how data was collected and how that led to results. It was interesting to experience how reviewing information from Excel sheets and building data visuals can impact our understanding of the world, especially in biomedical research.

What is your current position and how do you collaborate with each other and other lab members?

As a Data and System Manager, I can piece together reports that not only help clinical teams troubleshoot data issues, but also understand their study participants better as they go through clinical trials. I also get the opportunity to contribute to research discussions about efficient data collection methods and leveraging data to make a measurable impact where it counts.

What were the scientific goals you most want to accomplish in your Wistar work related to your MPH degree? What are your goals beyond?

Like my experience in public health, working in data means wearing many hats. You’re a translator, team player, problem solver, and trailblazer all at once. My biggest goal at Wistar is taking pieces of data from our research studies and communicating how that data is a steppingstone toward building a healthier life for everyone. And I get to do that one report at a time!

Unraveling the Ties That Bind: Epstein-Barr Virus and Multiple Sclerosis

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

A conversation with the Lieberman Lab delves into how EBV can trigger MS and potential therapeutic solutions that can be developed with this knowledge.

Epstein-Barr virus (EBV) is ubiquitous, establishing lifelong infection found throughout the world. It targets the immune system’s B cells and typically remains silent in immune system memory cells. Though infection with the virus is largely asymptomatic, specific biological and environmental conditions can enable the virus to cause more serious diseases. For instance, the virus can cause rare cancers that occur at much higher rates in immunosuppressed individuals. More recent research has found a connection between EBV and the neurodegenerative disease, multiple sclerosis (MS).

In a recent article published in Nature Reviews Microbiology, Paul Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor; program leader, Gene Expression & Regulation Program, Ellen and Ronald Caplan Cancer Center; and director, Center for Chemical Biology & Translational Medicine; and Samantha Soldan, Ph.D., staff scientist in the Lieberman laboratory, review evidence of EBV as a cause of MS and the implications of this knowledge in research and clinical spheres.

“Eliminating EBV latent infection should be a safe and effective way to treat EBV cancers and autoimmune disease, especially multiple sclerosis,” Lieberman says.

We spoke with Soldan about the link between EBV and MS as well as how this knowledge can be harnessed into potential therapeutics for the disease.

Q: What is some of the background linking EBV to cancer?

A: EBV was the first virus to be implicated as a causative agent of human cancer. EBV has been linked to nasopharyngeal cancers, stomach cancers, primary CNS lymphomas, Hodgkin’s and non-Hodgkin’s lymphomas, NK/T-cell lymphomas, and leiomyosarcomas, as well as several autoimmune disorders, including MS. It is currently estimated that 1.5-2% of all human cancers are attributable to EBV infection. All EBV-related cancers are associated with latent infection, where no infectious virus is produced by the tumor cells. Different types of EBV-associated cancers express different EBV latency genes. Notably, all EBV cancers express the viral protein EBNA1—required to maintain the EBV genome in latently infected cells and a primary interest of the Lieberman lab.

Q: What inspired this review to investigate evidence behind EBV as a cause of MS?

A: The case for EBV as a causative agent in MS has been mounting over the last 40 years. This year, two landmark studies were published: one providing a strong epidemiologic link to MS and the other suggesting a mechanism by which EBV may drive disease pathogenesis. These two studies have intensified the MS community’s interest in the link between EBV and MS, both as a disease trigger and as a potential driver of disease pathogenesis.

Dr. Paul Lieberman is a leading expert in EBV and in the study of EBV EBNA1 specifically, and he was invited to write a review article focused on the role of EBV in MS for Nature Reviews Microbiology. Paul asked me to be a co-author for this manuscript and I was delighted to have this opportunity. My background is in neurovirology, and I have been involved in research investigating the relationship between viruses and neuroinflammatory diseases, including MS, since graduate school. I am deeply invested in trying to better understand the role that EBV plays in MS.

Q: Why is multiple sclerosis a complex disease to study?

A: Multiple sclerosis is the most common demyelinating disorder of young adults, effecting more than one million individuals in the U.S. alone. MS is a heterogenous and often disabling disease that develops because of the interplay between the immune system and the environment in genetically susceptible individuals. The clinical progression of MS is variable and unpredictable with several distinct disease courses. In addition, MS patients often transition from a relapsing-remitting to a progressive disease course over time and the mechanism of the disease and central nervous system damage also evolve, which are a hallmark of MS.

Further complicating matters, epidemiological studies have shown that environmental factors (including EBV infection) that contribute to one’s risk of developing MS often occur many years before clinical onset. Collectively, these complex interactions between genetic, immunologic, and environmental risk factors makes attributing disease-contributing agents and designing preventative measures and effective therapies for MS very challenging.

Q: How does EBV trigger MS? Can you explain these processes?

A: How a ubiquitous agent like EBV triggers disease in a small percentage of those who are infected is an enigma. We face this challenge in understanding the role of EBV in cancer as well as MS. For MS and many autoimmune diseases, we can identify inflammatory and autoreactive immune responses and characterize immune responses to infectious agents and antigens that trigger immune response in patients. However, understanding what set immune cells on an autoreactive and inflammatory path before the patient is symptomatic is a difficult task.

Nevertheless, there are several theories as to how EBV may be both a trigger and a driver of MS and we discuss these in the review. We believe that it is likely that EBV is involved in the pathogenesis of MS at many levels and in different anatomic compartments.

Q: What are some potential therapies that could arise out of understanding the role of EBV in MS?

A: In recent years, therapies depleting B-cells have proven to be tremendously beneficial in MS. While EBV primarily infects B-cells, these B-cell depletion therapies eliminate cells regardless of whether they are infected by EBV, making it difficult to determine if any of the clinical benefit derived from these drugs is related to their effects on the virus.

There are several EBV specific therapies in development that have the potential to present new, effective options for patients with MS. In addition, they may also help us better understand the role of EBV as a trigger and driver of disease pathogenesis. These include vaccines to prevent the development of infectious mononucleosis, MS, and EBV-associated cancers; cell-based immunotherapies, including EBV-specific cytotoxic T cell lines; and EBV specific antivirals.

Q: Why is it important to review existing literature and reveal new directions for research?

A: I find review articles to be incredibly helpful, both to the writer and the reader. When writing a review, you must commit time and energy to refamiliarizing yourself with the latest literature as well as the history of the field. The process helps you take the proverbial 30,000-foot view and see the whole picture, forcing you to get your head out of the specific aspect of research that you are generally focused on and enabling you to generate new ideas and consider new approaches to your work. Reviews are also very important for colleagues and especially trainees to get perspective on where the field is headed and where there are gaps in our knowledge.

Q: What do you currently work on with Dr. Lieberman regarding MS and EBV and where is your research headed?

A: We are working in several directions to better understand the role that that EBV plays in the pathogenesis of MS. Our current work focuses on characterizing virus-host interactions and maintenance of EBV latency in EBV infected B-cells from MS patients compared to healthy controls. Dr. Chenhe Su, a postdoctoral fellow in the Lieberman lab, is also working very hard on these studies.

I am especially interested in developing better animal models to understand how host factors like age of exposure, genetic background, metabolism, and sex influence host-virus interactions and EBV reprogramming of B-cells. We are also testing EBV-specific antiviral therapies, including the EBNA1 inhibitor developed in the Lieberman lab, to determine its potential as a therapeutic agent for use in MS.

Exceptional Wistar Trainees Honored at 2022 Rugart Family Awards Ceremony

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

Dr. Laura Garcia Gerique, postdoctoral fellow in the Nefedova lab, and Sarah Offley, graduate student in Gardini lab, are winners of the 2022 Annual Rugart Family Awards.

This annual event, sponsored by the Rugart Family honors the late Karl F. Rugart, Jr., an obstetrics and gynecology physician and longtime supporter of Wistar. The award is given annually for the best Research-in-Progress presentation by a predoctoral student and postdoctoral fellow.

Postdoctoral fellow Dr. Laura Garcia Gerique presented her work on the role of Annexin A1 protein in tumor biology and how it may impact cancer development, metastasis, and treatment. The second winner, graduate student Sarah Offley focuses her research on characterizing a novel integrator complex subunit that has implications for cancer and disease research.

Since 2014, the Rugart Family Awards recognizes promising early-career scientists demonstrating exceptional presentations of their scientific projects. The winners are voted on by their peers, setting the Rugart Family Awards apart as a unique distinction defined by the competitive, yet collaborative, nature of Wistar’s trainees as they present ongoing research and improve their work.