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Author: The Wistar Institute

Unique Stephens: My Journey to a Career in Life Science

Unique Stephens, who recently testified at a Philadelphia City Council hearing about the life science sector, shares why her experience at Wistar was transformational.

Can you tell me a little bit about your high school experiences? Did you always have an interest in science?

I really didn’t take a science course until high school. I went to high school in West Philly, and wasn’t interested in science, but my school had a program called a CTE – career and technical education. They offered two different courses: a health-related technology (HRT) program and a sports therapy program. I was enrolled in the HRT program. It was supposed to be a 4-year program that ran from 9th to 12th grade, but I started in 11th grade, so it ran on a compressed timeframe.

We were in class about four hours every day to get the needed number of hours to qualify as a CTE. This was the first science related, hands-on course that I took. And it wasn’t even in a traditional science like biology or microbiology – it was focused on nursing. During our training we had a conversation about cancer, and I went down a rabbit hole. I started thinking, ‘All you have to do is kill the cancer cells. Why is it so hard?’ So that was what got me interested in the sciences.

When I started thinking about a future career, I was initially more attracted to engineering or architecture because I love learning about the structures of things. But in my classes, when we talked about the human body — internal organs and cells — I realized the body is like the most complex structure.

COVID hit in my senior year of high school, and I was comfortable with receiving the necessary vaccines and booster shots. But a lot of people in my community were more reluctant because they didn’t understand the science behind it. That heightened my science interest more. If I understood the science, I would be able to break it down so that they wouldn’t have to be too scared to protect themselves.

You’re currently a senior at Cheyney. How did you get involved with Wistar?

I’m studying biology with a concentration in pre-health profession. When I was a junior and registering for courses at Cheyney, I noticed a class called biomedical research methods. My advisor suggested I take it because of how important it is to get hands-on lab experience – and this is central to the course. After completing the course, I continued on with a summer internship at Wistar working under Dr. Ian Tietjen, a Wistar researcher in Dr. Montaner’s HIV lab.

Dr. Tietjen and I talked about continuing my work in the lab because I liked it so much. Then, a couple of weeks into first semester of my senior year, he emailed to say they would very much like to have me back. I was able to continue my work in the lab, and as I got closer to graduation, Dr. Tietjen asked about my plans afterwards. I originally considered a gap year but knew this was a great opportunity to continue in the lab through the Biomedical Research Technician Apprenticeship. I qualified for the Apprenticeship because of my coursework, so now I’m working in the Montaner lab for the foreseeable future.

I’ve started working with Paridhima Sharma, a research assistant in the Montaner lab. Her work is very different from what I’ve done before, and I’m very thankful because she is going to teach me a lot.

What does your family think of your path?

Everybody in my family loves the work that I do. My older sister was also in research, but it wasn’t as focused as what I do. They recognize that I’ve always been very “hands on” and had a tendency to question everything, so research is a good fit. I think they admire the work I do because it’s so different. I break the science down for my dad and he catches on quickly. But what’s also interesting is that he gives me ideas regarding my research experiments.

What does diversity, equity and inclusion mean to you, and why is it important?

As you see more diverse people around you – people who look like you – it makes you feel like you can belong in this space. It gives you the confidence that even if you feel like you don’t know what you’re doing, you can always learn. Diversity covers so many different forms – you can get input from the the most unlikely places! Let’s take my dad, for instance, the reason I talk to my dad and my friends about the work that I do is even if they don’t understand the science, they still have good ideas about the questions to ask when doing science. My dad has no science background, but he has common sense and brings an outside perspective, so it all matters. That’s similar to when you talk to someone who has a science background but is from a different country. They may have a totally different lab experience, yet they may show you a new technique that helps you achieve your goal. I think that representation, and feeling comfortable — all really matters, and it moves everything forward.

You mentioned you want to go to grad school. Do you see yourself as continuing in the research field or do you think you may end up teaching?

I would like to do both. I’m really interested in education. For the last two years, I’ve been tutoring high-school students in biology, chemistry, and even math. It’s inspiring to see my students learning about different chemicals & bonds and basic biology. I believe you can learn whatever you want, you just need a good teacher to help you understand. It’s definitely something that I would love to do. I love research, but I think teaching would be very fulfilling alongside carrying out straight research.

You recently testified before Philadelphia City Council, at a hearing about training for future life science careers. What was that experience like?

I was anxious – as you can imagine – but it was great. If I did it again, I would be more confident. When I know what I’m speaking about, and I stick to my experiences, and in my own words, then I’m confident. I didn’t practice my testimony beforehand, but next time I will so that I can feel comfortable. It was a great experience — I loved it. And I tell everybody I spoke at City Council!

Any outside interests or hobbies?

Most of my hobbies are on hold because of classes and work, but I’ve been planning! Once I graduate, so much time is going to be freed up. I’m learning how to roller skate because all my friends know how. I’m practicing in my basement because I’m too embarrassed to go to the actual skating rink and fall. I also like to sew, and I have a sewing room. My grandma taught me how to crochet and knit. I’m also really interested in cooking, even though I’m not very good at it yet. My mom keeps encouraging me, though, so the more I do it the better I’ll get.

“Immunology is a Battlefield”: Wistar’s Dr. Nan Zhang on Creativity and Curiosity in Science

Dr. Nan Zhang, Ph.D., is an Assistant Professor in the Immunology, Microenvironment and Metastasis Program at the Ellen and Ronald Caplan Cancer Center. He studies the role of immune cells called macrophages in tumor growth and metastasis in the abdominal cavity and the ovaries.

Why did you choose to become a scientist?

My dad played a big role in my development. He was an urban planning professor , which planted the seed early on that becoming a professor would be great. We lived in China, but he came to the States when I was born and worked in upstate New York for a year and a half. It was an eye-opening experience for him. He brought back the ideas of experimenting and doing science, and those seeds just grew naturally in me.

In middle school and high school, I was good at STEM subjects, and when I applied to college, I chose to focus on biological sciences. As a sophomore, we could choose a sub-major within biological sciences, and there was a program in immunology that fascinated me, so I picked it. However, by the end of college, I was tired of rote memorization without understanding why I was memorizing it. You can know how to do things, which is the focus of a lot of schools in East Asia, but I think the more important question is: Why do you do it? This is why I chose to come to the States to enroll in a Ph.D. program. I wanted to learn how to think like a scientist.

How would you explain your research in immunology to somebody who is not a scientist?

Immunology is how your body reacts to foreign invaders. Your immune system is always fighting against unwanted intruders—pathogens, viruses, cancer cells—so I use the metaphor of a battlefield.

On a battlefield, there are soldiers who specialize in one type of strategy or terrain. These make up our adaptive immunity: T cells, basically the core cell type for current, groundbreaking immunotherapies. These cells are specific to a certain situation, like a particular virus or tumor cell, and they’re really good at fighting it.

What my lab studies are the types of soldiers who are equipped with general knowledge of fighting, which is called innate immunity. They’re not especially good at one type of fighting, but they might be good at learning and picking up new skills along the way. And as they learn, they will differentiate or develop into a more specialized type of cell.

I study macrophages, who are always on the battlefield. They stay there, respond when there’s an invasion, and then pass relay signals calling for help. When they’re calling for help, there are cells called monocytes, which are generalized but eventually differentiate into different types of macrophages, or soldiers. Then those cells send signals to the specialized soldiers, the adaptive immune system, who are better at killing pathogens.

My lab studies these innate immune cells because there’s a big gap in understanding what they are doing. They can develop into different types of cells, but how they develop, how they decide what cells they become, is not really known. Yet they are really important. These macrophages organize the battlefield, so to speak, so the adaptive immune soldiers know how to fight and what to fight.

It sounds like you have a lot of practice talking to laypeople about your work. Do you find that these conversations inform what you’re studying and how you talk about it?

Well, my son is one of the people who listens to me talk about my science. He will ask, “Why do you do this? Why is it important?” So I have to think of how I explain to an eight-year-old that what I do is important.

The most useful thing I’ve learned in talking to laypeople is that I need to understand and relate what I’m doing to the important medical issues they have. Laypeople don’t care about the detailed messages soldiers are sending to each other; they care about curing a disease and why the disease is killing people. And sometimes, when you’re writing grant proposals, it’s important to look back and see: Why are we doing this? Why should they give money to study this? I think that’s what talking to non-scientists has helped me do.

What do you think is the relationship between creativity and science?

Trying to be unique and different is what drives me to be creative, and being creative is how you find solutions in science. Connecting subfields is one way of standing out. Some of the most prominent scientists in my field are using ecological methods or equations to study how immune cells behave as a group, as a population. That kind of research is fascinating to me. It’s why I could never give up my deep interest in basic research and why I always have at least one basic research project in my lab.

Looking for new ways to do things and being creative also got reinforced when I was a postdoctoral fellow. My postdoctoral mentor is very creative. She connects dots like nobody I’ve met, and she made me recognize that there’s always an alternative hypothesis. You don’t have to be frustrated by a negative result. Just stay curious. It’s how we got to the moon and found so many cures: because we were curious for such a long time.

For more information, email comm-marketing@wistar.org.

Wistar Scientists Start New Conference on Foundational RNA Research

Back from hosting the first-ever Genome Regulation through RNA Conference in Cancun, Mexico, Wistar faculty members Alessandro Gardini, Ph.D., and Kavitha Sarma, Ph.D., give us the inside scoop on what it was like to host a scientific meeting from scratch.

What made you want to create a new conference?

Alessandro Gardini: Hundreds of biomedical research conferences happen every year. They are hallmark meetings — featuring a great lineup of presenters and topics — but sometimes you want a fresh perspective. Kavitha and I were interested in a distinct conference focus, and thought, “why not create something together?”

With our friend and collaborator Dr. Roberto Bonasio, associate professor at University of Pennsylvania, we developed a new concept. Once we had a pitch, we created a “wish list” of top people in our field whom we’d want to invite, and in which topics we’d want to coalesce talks and panels.

What is a successful conference?

AG: If you want people to attend your conference, you need prestigious scientists. Researchers who’ve made big waves in the field can entice people to attend.

KS: Attending conferences is critical to being a scientist, but you only have a certain amount of travel per year, so you want to attend the most impactful meetings.

AG: We had 90 people – a great turnout for a first-time event.

You named your meeting the “Genome Regulation through RNA Conference.” Can you describe the scientific niche you were aiming to fill?

AG: Plenty of conferences are entirely RNA-focused, but we created this conference at the intersection of RNA and epigenetics – where we do most of our work.

KS: This meeting focused on the most foundational, basic levels of RNA-driven genome regulation: which genomic functions do RNAs perform, how are DNA-RNA hybrid structures implicated in gene expression. We didn’t even delve into the therapeutics side because we were focused on the fundamentals. This gathering of like-minded people presented abstracts centered on the mechanistic aspects of RNA within the human genome.

AG: That RNA focus – for the mere sake of understanding its genomic effects – led to some very interesting discussions. For example, the mitochondria in our cells have their own genomes, which we tend not to think about too much. But by having their own genomes, they naturally have genomic regulatory mechanisms, too, which involve certain mitochondrial RNAs. Those are the ideas and research topics that I love encountering at conferences. My research, on its own, may not have taken me there.

Why are conferences so important to scientists?

AG: In biological terms, it’s the “lymph” of our work—it enhances our research. Conferences are extremely important for fostering collaboration. Yes, there’s a body of literature, and our job is to stay current on published papers in our field. But that’s a small snapshot of knowledge compared to the free flow of information at conferences.

All science, but especially biomedical research, is highly specialized now. We’re a long way from the days of eccentrics conducting experiments in castles. Today, researchers can spend their entire lives analyzing something as minute and specific as the mitochondria.

Conferences give scientists much-needed exposure to other areas of research. We learn how to conduct science better, how to incorporate new ideas. And that keeps scientific passion alive. Seeing all the exciting work that others are doing refreshes my sense of enthusiasm and gives me ideas that I can begin to pursue.

KS: They’re also indispensable for collaboration. I can’t tell you how many times at a conference, a conversation leads to two people publishing on the same paper as co-authors. Without that conference, they may never have met.

You can never know how your work might be applicable in other fields because those areas aren’t your areas of expertise. Conferences open researchers’ eyes to opportunities to improve each other’s work, and everyone wins. By being there, talking and meeting new people, going to networking dinners, that turns into new ideas, new papers, and better science.

Wistar Scientists Identify Pro-aging ‘Sugar Signature’ in the Blood of People Living with HIV

PRESS RELEASE
The Abdel-Mohsen lab findings shed light on how sugar molecules in the blood of people living with HIV may accelerate biological aging

PHILADELPHIA — (April 10, 2024) — The Wistar Institute’s associate professor Mohamed Abdel-Mohsen, Ph.D., along with his team and collaborators, has identified sugar abnormalities in the blood that may promote biological aging and inflammation in people living with HIV (PLWH). The findings, taken from a large data study comprising more than 1200 participants, are detailed in the new paper, “Immunoglobulin G N-glycan Markers of Accelerated Biological Aging During Chronic HIV Infection,” published in the journal Nature Communications.

Despite advances in HIV treatment, notably the success of antiretroviral therapy (ART) in suppressing the virus to undetectable levels, HIV remains incurable, with the virus persisting in a dormant state within the body. This chronic presence is linked to long-term health issues, including persistent inflammation and a higher prevalence of aging-related diseases such as cancer and neurocognitive disorders. These conditions tend to occur more frequently and at an earlier age in PLWH compared to the general population.

Abdel-Mohsen seeks to understand how chronic viral infection causes this accelerated biological aging, which refers to the body aging faster than one’s chronological years would typically indicate. By understanding the molecular mechanisms behind accelerated biological aging in people living with chronic viral infections, scientists can begin to formulate strategies to mitigate the negative effects.

While many factors in the body can contribute to accelerated biological aging, researchers focused on a novel factor: abnormalities of the human glycome — the totality of the various sugar structures circulating throughout the body. Previous studies have established a connection between aging and shifts in the glycan composition of immunoglobulins (IgGs), which are critical for immune regulation. As people age, their IgGs lose anti-inflammatory properties and gain pro-inflammatory characteristics.

Abdel-Mohsen’s research investigates whether living with a chronic viral infection, such as HIV infection, exacerbates these changes, leading to premature aging and related diseases. By comparing glycan profiles in more than 1200 individuals, both with and without HIV, the team discovered that PLWH exhibit elevated levels of inflammatory and pro-aging IgG glycan signatures. In a remarkable step forward, the team developed a machine-learning model that uses these glycan signatures to estimate the biological age of PLWH and assess the rate of aging acceleration. This glycan signature also has the potential to predict the onset of comorbid conditions in PLWH, such as cancer, years in advance.

To confirm that these glycan-associated disruptions were causal rather than merely correlative, the research team engineered HIV-specific antibodies designed to exhibit the same kind of aberrant IgG glycan modifications observed in PLWH. Testing these glycoengineered antibodies in vitro confirmed that the modified antibodies were less effective at mounting an immune response than their unmodified counterparts, suggesting that these sugar abnormalities might directly contribute to the worse clinical outcomes observed. Importantly, when they designed these antibodies to have glycans similar to those found in biologically younger individuals, these antibodies demonstrated a remarkable ability to enhance the immune system’s ability to fight virus-infected cells.

“Utilizing glycan signatures to predict early onset of diseases in people living with HIV marks a pivotal shift towards proactive healthcare,” said Abdel-Mohsen. “This could significantly alter clinical outcomes, allowing for timely interventions and personalized treatment plans. The impact on treatment and management in the HIV community could be revolutionary. Beyond biomarkers, antibodies glycoengineered to mimic biologically younger glycans offer a new therapeutic avenue. This method could enhance immune responses, paving the way for innovative treatments.”

Co-authors: Leila B Giron, Qin Liu, Opeyemi S Adeniji, Xiangfan Yin, Toshitha Kannan, Jianyi Ding, David Y. Lu, Joao L. L. C. Azevedo, Andrew Kossenkov, and Mohamed Abdel-Mohsen of The Wistar Institute; David Y. Lu of Cornell University; Susan Langan, Jinbing Zhang, Sabina Haberlen, Stephen Gange, Wendy S. Post, and Todd T. Brown of Johns Hopkins University; Shuk Hang Li and Ian Frank of the University of Pennsylvania Perelman School of Medicine; Sergei Shalygin and Parastoo Azadi of University of Georgia; David B Hanna of Albert Einstein College of Medicine; Igho Ofotokun of Emory University School of Medicine; Jason Lazar of SUNY Downstate Health Sciences University; Margaret A. Fischl of University of Miami; Bernard Macatangay and Charles Rinaldo of University of Pittsburgh; Adaora A. Adimora of University of North Carolina, Chapel Hill; Beth D. Jamieson of University of California, Los Angeles; Daniel Merenstein of Georgetown University Medical Center; Nadia R. Roan of Gladstone Institutes and University of California, San Francisco; Phyllis C. Tien of University ofCalifornia, San Francisco; Olaf Kutsch of University of Alabama at Birmingham; Steven M. Wolinsky of Northwestern University; Mallory D. Witt of Lundquist Institute of Biomedical Research at Harbor-UCLA Medical Center; and Alan Landay of Rush University.

Work supported by: This work is mainly supported by the NIH R01AG062383 and the NCI supplement to the Wistar Institute Cancer Center (P30 CA010815) to M.A-M. M.A-M is also funded by the NIH grants, R01AI165079, R01NS117458, R01DK123733, Penn Center for AIDS Research (P30 AI 045008), and the NIH-funded BEAT-HIV Martin Delaney Collaboratory to cure HIV-1 infection (1UM1Al126620). Mass spectrometry-based glycomic analyses was partially supported by NIH R24GM137782 and GlycoMIP, a National Science Foundation Materials Innovation Platform funded through Cooperative Agreement DMR-1933525. We would like to thank Drs. Michel Nussenzweig, Costin Tomescu, and Luis J. Montaner for providing the wild-type 10-1074 for the glycoengineering experiments and Dr. Daniel Kulp for providing HIV-1 Env trimer, BG505. Data in this manuscript were collected by the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MWCCS (Principal Investigators): Atlanta CRS (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos, David Hanna, and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D’Souza, Stephen Gange and Elizabeth Topper), U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky, Frank Palella, and Valentina Stosor), U01-HL146240; Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01-HL146242; Los Angeles CRS (Roger Detels and Matthew Mimiaga), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; UAB-MS CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, Deborah Konkle-Parker, and James B. Brock), U01-HL146192; UNC CRS (Adaora Adimora and Michelle Floris- Moore), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR). MWCCS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR003098 (JHU ICTR), UL1TR001881 (UCLA CTSI), P30-AI-050409 (Atlanta CFAR), P30-AI-073961 (Miami CFAR), P30 AI-050410 (UNC CFAR), P30-AI-027767 (UAB CFAR), P30-MH-116867 (Miami CHARM), UL1 TR001409 (DC CTSA), KL2-TR001432 (DC CTSA), and TL1-TR001431 (DC CTSA). The MACS CVD2 study is funded by National Heart Lung and Blood Institute (NHLBI), R01 HL095129-01 (Wendy Post). The authors gratefully acknowledge the contributions of study participants and dedication of the staff at MWCCS sites.

Publication information: “Immunoglobulin G N-glycan 1 Markers of Accelerated Biological Aging During Chronic HIV Infection,” from Nature Communications.

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ABOUT THE WISTAR INSTITUTE:

The Wistar Institute is the nation’s first independent nonprofit institution devoted exclusively to foundational biomedical research and training. Since 1972, the Institute has held National Cancer Institute (NCI)-designated Cancer Center status. Through a culture and commitment to biomedical collaboration and innovation, Wistar science leads to breakthrough early-stage discoveries and life science sector start-ups. Wistar scientists are dedicated to solving some of the world’s most challenging problems in the field of cancer and immunology, advancing human health through early-stage discovery and training the next generation of biomedical researchers. wistar.org.


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Early-Stage Discovery: How Wistar’s Genomics Facility Drives Wistar Science

Meet Sonali Majumdar, M.S., managing director of The Wistar Institute Genomics Facility, a hub that turns biological material into the data scientists need. Ms. Majumdar discussed the ins and outs of genomics technology and how Wistar Science depends on it.

Wistar’s Genomics Core Facility houses the latest and greatest scientific instruments, some of the most advanced (and expensive-to-use) biomedical technology in the building — in this understated laboratory are machines that manipulate the very fabric of life. These machines are genomic sequencers: counters of DNA and RNA molecules that form the foundation of our biology. Genomics Facility managing director Sonali Majumdar, M.S., has presided over a top-notch team of sequencing experts for nearly ten years, and their work sustains the foundational research of scientists both in- and outside the Institute.

“Genes are the beginning,” says Sonali. “Generally, when people want to discover something, they’ll do a genomics study — so they come to us.”

Every cell in our bodies contains our genome, a vast amount of biological information comprising every set of base pairs on every chromosome. But humans aren’t homogenous biological masses of cells; our bodies have different types and arrangements of cells for different functions. In short: not every gene in our genome gets “expressed,” or turned on, because complex life demands complex variety. To understand how or why certain things happen in our cells, scientists need to understand which genes do what — that’s what Sonali and her team at Genomics Core Facility do.

“Our cells have more than twenty thousand genes that can theoretically get turned into proteins,” she explains. “As a scientist, you want to know which of those genes affect your project. Take cancer, for example. We can broadly sequence cancer tissue and compare that with similar tissue from an apparently healthy individual. The scientist can see, that out of twenty thousand genes, maybe one hundred or so may play a role in the cancer. Then we can look at sequencing data for each gene individually.”

At the most basic level, sequencing “counts” genomic elements. Though newer machines like Wistar’s nanopore sequencer can perform long-read sequencing (read unabridged descriptions of base-pair sequences of T, C, A, and G), most sequencing methods identify key snapshots of the genome and then use computational methods to reassemble the full sequence.

At the broadest levels of sequencing, the process is like looking for needles in haystacks; scientists look for patterns that occur on enormous scales. But the opportunity to find something genuinely new keeps her passionate.

Managing the Genomics Core is a huge undertaking, and not just because of the volume of tasks. In the world of biomedical research, where scientists’ scope is largely determined by how much money they have for their projects, genomic studies and sequencing can take up hefty portions of budgets. When her team executes their analyses, science isn’t the only thing at stake — so is grant money.

“The materials and solutions that genomics studies use are incredibly expensive, and the steps we take to sequence samples properly require absolute precision; if a process isn’t followed correctly, that mistake might cost hundreds or thousands of dollars,” says Sonali. “There’s one step for our single-cell sequencer where, if you don’t add the solution extremely carefully, that’s an instant $2,000 down the drain.”

Grant dollars may be precious, but scientists happily pay for genomics and sequencing because the technology is so vital to such a broad swath of biomedical research, and Wistar’s Genomics Core Facility delivers quality data thanks to a team of dedicated experts and state-of-the-science equipment. In 2023, Wistar completed the installation of new spatial molecular profiling technology which allows for spatial phenotyping of millions of cells at an unprecedented scale and speed. This equipment was purchased thanks to the generosity of The Horace W. Goldsmith Foundation through Wistar’s Bold Science//Global Impact Campaign and the estate of Robert A. Fox.

“We take our work very seriously because, yes, money and data are on the line. Delivering results to scientists takes precision, and that’s what we strive for,” says Sonali. With more than a dozen specialty genomics services available, Wistar’s Genomics Core Facility is state-of-the-science — a state that, according to Sonali Majumdar, should excite anyone invested in biomedical discovery.

“Genomics has come a long way,” she says. “Single-cell sequencing can show us expression levels in specific cells, so we can tell which genes are doing what in a variety of cell types or tissues. And with the rise of spatial sequencing, we can even create a map of gene expression across a tissue: this gene is highly expressed in this region, not very expressed in that region, and so on.”

As Wistar continues to pursue early-stage discoveries through its new Center for Advanced Therapeutics, genomics will only become more important. In seeking to revolutionize drug discovery by using the latest and greatest in biomedical research methods, the new Center for Advanced Therapeutics will depend on the advanced capabilities of the Genomics Core Facility to indicate whether possible drugs work and how they can be improved.

“This is just the beginning of new genomics techniques throughout biomedical research,” says Sonali. “As sequencing technologies become less expensive and more advanced, we’re only going to see more exciting developments. That’s why I love this field: genomics is where the action is.”

Wistar Scientists Explore Importance of Microglia Marker in Metastasized Brain Tumor Microenvironment

PRESS RELEASE

The Chen lab examines microglia activation in metastatic brain tumors

PHILADELPHIA—(Mar. 28, 2024)— The Wistar Institute’s Qing Chen, M.D., Ph.D., assistant professor in the Immunology, Microenvironment and Metastasis Program at the Ellen and Ronald Caplan Cancer Center, has discovered certain immune cells in the brain called microglia have reduced expression of TMEM119 in cases where cancer has metastasized to the brain. The Chen lab’s finding provides an opportunity to more accurately study how brain microglia behave in metastatic contexts, which is key for researching possible therapies. The new paper, “Tmem119 expression is downregulated in a subset of brain metastasis-associated microglia,” was published in the journal BMC Neuroscience.

“This research provides a new avenue and crucial first step in understanding how these immune cells interact with cancer, and we look forward to future mechanistic studies of these cases,” said Dr. Chen.

When cancer cells metastasize into the brain, the nervous system’s immune cells, called microglia, become activated. Immune cells are a very important area of study for cancer researchers because understanding how they do (or do not) function against cancer allows scientists to develop strategies to improve the immune system’s ability to fight cancer.

However, studying the mechanistic role of microglia in metastatic cancers in the brain has been difficult because, by most measures, microglia are difficult to distinguish from another set of immune cells — myeloid-derived immune cells — that also enter the brain in pathological conditions.

Dr. Chen and her lab study how cancer cells interact with brain stromal cells, and wanted to investigate TMEM119 — a cell surface marker which has been recently identified to express specifically on microglia. They aimed to investigate the TMEM119 expression in the microglia from brain metastasis tumors.

They analyzed a preclinical model of breast cancer that metastasizes to the brain, and by assessing the gene expression of the immune cells, her team was able to confirm that only brain microglia, but not infiltrated myeloid cells, express TMEM119. Moreover, metastasis-activated microglia have an identifiable reduction in TMEM119 expression.

Co-authors: Weili Ma, Jack Oswald, Angela Rios Angulo, and Qing Chen of The Wistar Institute.

Work supported by: National Institutes of Health & National Cancer Institute grants T32CA009171, R01CA241490, and Specialized Program of Research Excellence P50 CA261608.

Publication information: “Tmem119 expression is downregulated in a subset of brain metastasis-associated microglia,” from BMC Neuroscience.

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ABOUT THE WISTAR INSTITUTE:

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 disease, and produce groundbreaking advances in world health. Consistent with a pioneering legacy of leadership is 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 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


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Formulating a love for science

Kensington Health Sciences Academy students get hands-on experience and exposure to Wistar Science

Standing in The Wistar Institute’s state-of-the-art training lab, a small group of 12 students gathered quietly around a large digital display projecting two stacked lines of text, each made up of the letters T, G, C, and A. The sequences showed the base components of two different DNA strands: one a reference sequence representing the most commonly found sequence in humans; the other, a sequence from a cancer cell’s DNA. Pointing to the lines, Jason Diaz, Ph.D., Director of Education and Inclusive Excellence in the Hubert J.P. Schoemaker Education and Training Center, asked the students how to tell whether the cancer cell’s DNA was mutated by comparing the two sequences.

Slowly, a hand went up. “Because of the gaps, where the letters don’t match?” said one of the students hesitantly. “Yes!” responded Dr. Diaz enthusiastically. “There’s a mismatch in the two sequences. The cancer cell’s DNA is different at this position compared to the reference. What do you think are the implications of having a mutation in this gene?”

These Kensington Health Sciences Academy (KHSA) students were in the last phase of a 6-week program designed to boost their exposure to science, and in particular, engage in biomedical research.  Over the course of two half-day visits to Wistar, more than 50 students had a chance to hear from research trainees, tour working research labs, and perform a final lab activity in the training lab.

Every week for the extent of the 6-week program, Dr. Diaz visits students in the classrooms at KHSA to provide educational sessions that highlight the value of – and the need for – biomedical research skills. The experiential program, delivered in partnership with Heights Philadelphia, a non-profit devoted to bolstering educational opportunities in underserved communities, is designed to strengthen students’ exposure to science curriculum and position them for future education and careers in the sciences.

While Philadelphia’s burgeoning Life Sciences industry has been a boon for the city’s growth, ensuring that students, particularly those in underserved communities, have access to and preparation for life science careers has historically been a challenge. The program is aimed at closing the gap and ensuring that students have early exposure to the skills needed to pursue in-demand careers in the region.

Jeremy Heyman, Ph.D., Director of STEM Pathways at Heights, explained that the program has been evolving for quite some time. “This came out of conversations with the Wistar team shortly after we met in 2021.  We envisioned adapting the promising course-based undergraduate research experience (CURE) model to the high school level,” explained Dr. Heyman. “This approach, meeting 9th grade students where they are in their science classes, seems like a very promising way to expand access and exposure to Life Science career opportunities for the students we serve from local underinvested communities.”

In fact, the program’s success has led to additional support from Philadelphia-based Spark Therapeutics, a developer of gene therapies. “We appreciate Spark’s support for this academic year and are looking forward to the next phase which includes an even more extensive course-based research experience that is also scalable to reach more schools and students,” explained Heyman.

In the classroom, Dr. Diaz has been working with science teacher Barbara Sharpe to integrate a curriculum that focuses on the TP53 gene, and a genetic variation that can increase the risk of certain types of cancer. Students have a chance to learn about polymerase chain reaction (PCR), which copies pieces of DNA for study, and gel electrophoresis to visualize and analyze the DNA. DNA samples prepared by students are ultimately sequenced at Wistar’s Genomics Core Facility. They also learn about bioethics and biomedical research in general.

“We’re exposing them to real-world techniques that our scientists use in the lab every day,” explained Dr. Diaz of the curriculum. “We’re not only hoping to spark an interest in science, but we’re also giving them foundational knowledge that can give them a leg-up if they plan to pursue science-based studies in the future.”

In 2024, as part of the expansion efforts, Wistar and Heights plan to offer the program at George Washington Carver High School of Engineering and Science. The team is also evaluating student feedback from prior years to make the class as relevant as possible and to ensure it aligns with current standards in biology education.

“We want to develop a complete pathway for learning science, with multiple entry points,” explains Dr. Diaz. “Students will leave richer for it, wherever they may go.”

A home away from home: For Tom Beer, a role at Wistar turned into a second family.

We talked with Tom Beer, research assistant in the Proteomics lab, on his path to Wistar, his daily work, and his love for sports.

When did you arrive at Wistar?

My first job out of college was as a Food Safety Consultant, and I traveled up and down the East Coast visiting supermarkets and drug stores. The firm went out of business, so I had to find a new job, and discovered a position at an electron microscopy services laboratory in New Jersey. I spent several years there before they decided to relocate the business. I started looking for another opportunity somewhere stable and unique. I have a science degree – Physiological Plan Ecology – and I liked the idea of working in the lab. I saw a position at Wistar working with mass spectrometry – before I even knew what mass spectrometry was –  and decided to give it a shot. I interviewed and it seemed like a good fit, and an interesting opportunity. That was in 2002, and I’ve been here ever since.

Walk me through a day at work – what does your day look like?

A researcher or a lab will approach our team with a request to determine what’s in a sample or a set of samples. For instance, they’ll need to know every single protein and maybe the levels of those proteins. I take those samples, and I can process and use mass spectrometry to break it down and provide a detailed report. A lot of my work is preparing samples for mass spectrometry. The samples need to be clean, and we don’t always get clean samples so I need to do some prep work. That involves breaking down the cells in a solution, getting them ready, ionizing them and putting them on the instruments. That’s where the magic happens! Then we produce a detailed report that shows the proteins, the levels, and any other details they may need. Some requests are more complicated than others. If there is data manipulation or analytics that must be done, usually that’s another member of the team. Those requests take more time. In fact, we just installed some new equipment that will help us streamline the data analysis process and make it a bit quicker.

What is your favorite part of your job?

Even though the work we do is the same, every project is unique. When I first started, after each analysis we would hand deliver reports to the researchers. They would get excited when I’d hand them the data, and that was really satisfying. I’m giving people data that they can use for a research project! Sometimes the workload can become intense, but I love it – this is my second home. I really enjoy the people and the interactions. I even met my wife here!

How has Wistar changed since you first arrived?

I think it’s more structured now, and that’s a good thing. I’ve seen the new Fox Tower go up; I’ve seen the labs grow. We’ve just gotten more sophisticated and we’re able to do more.  

What is it that makes Wistar special?

The people. This is my second family. I’m in a unique position: I may not be a researcher or have that background, but through my work I interface with PIs and research staff all the time. I can relate to anyone – scientists, admin staff – it doesn’t matter. This is where I spend the majority of my time, so it’s important that I enjoy coming to work.  

What do you do outside of work to recharge: cooking, reading, any hobbies?

I’m really into my kids’ sports, and sports in general. I have an 11-year-old son and a 13-year-old daughter. My son loves basketball and flag football, and my daughter likes soccer. She’s fast, so we’re trying to get her into running. I’ve done coaching over the years, but I enjoy the support roles more, like assistant coaching or just helping out at the bench. And every Friday we have a tradition with the kids: homemade pizza. Lastly, I spend a lot of time on yardwork. I have to keep up with my neighbors!

What does diversity, equity and inclusion mean to you?

I think it means everything. It’s something that was missing from science for a long time. More diversity has to be the future: you have to get different perspectives and new ideas. Anytime you can draw from different world experiences and different backgrounds, you’re only making things better.

Wistar in the News: Inquirer story on new Wistar-PCOM Cancer Biology Ph.D. Program

The Wistar Institute was featured in The Philadelphia Inquirer for the launch its new Cancer Biology Ph.D. Program with Philadelphia College of Osteopathic Medicine. Reporter Sarah Gantz detailed how the jointly run Ph.D. program will offer innovative, hands-on, cancer biology and drug development courses to support students for careers of the future.

Article link: https://www.inquirer.com/health/pcom-wistar-graduate-cancer-program-20240321.html

This story may be behind a paywall.

PCOM, The Wistar Institute Announce Cancer Biology Graduate Program

Marking the next step in their innovative academic collaboration, Philadelphia College of Osteopathic Medicine (PCOM) and The Wistar Institute have announced the launch of a highly anticipated Cancer Biology Ph.D. Program aimed at advancing research and cultivating the next generation of leaders in the fight against cancer.

“This announcement signifies a pivotal moment in our collaboration with Wistar, and a continuation of our commitment to offer world-class medical education and research,” said PCOM President and CEO Jay S. Feldstein, DO. “Together, with the expertise and resources of Wistar combined with the academic excellence of PCOM, we will continue to push the boundaries of scientific knowledge to confront the complexities of cancer and improve outcomes for patients everywhere.”

“Our hope is that by harnessing the collective expertise of PCOM’s esteemed faculty and the renowned researchers at Wistar, we can accelerate discoveries, develop innovative therapies, and, ultimately, bring hope to those affected by cancer,” said Gregory McDonald, DO, dean of the School of Health Sciences at PCOM. “This collaboration exemplifies our shared dedication to achieving those goals.”

“This collaboration with PCOM means Philadelphia now has a new biomedical science Ph.D. program to support our region’s growing life science sector. Wistar’s innovative research programs are in lockstep with PCOM’s new life science sector degree program,” said Dario C. Altieri, M.D., Wistar President and CEO, director of its Ellen and Ronald Caplan Cancer Center and the Robert and Penny Fox Distinguished Professor.

The Cancer Biology Graduate Program—jointly administered by Wistar and PCOM—will train individuals for a successful academic or industrial career in cancer biology and drug development.

This comprehensive, integrated program is centered on the involvement of both Wistar and PCOM faculty and provides an inclusive, broad-based graduate educational venue that complements and expands existing opportunities for cancer training in the Greater Philadelphia region. At the conclusion of their studies, successful candidates will be granted a Ph.D. in cancer biology from PCOM.

Focusing on cutting-edge strategies to understand the molecular basis of cancer initiation and progression, this program will also emphasize the process of drug discovery and development.

“Teaming up with Wistar is an exceptional opportunity for students to learn in collaborative and multidisciplinary environments, develop expertise in research related to cancer biology, and participate in technology development leading to innovations in detection and treatment,” said PCOM’s Chief Research and Science Officer Mindy George-Weinstein, Ph.D.

This news follows the earlier announcement of a collaboration to offer degree programs, courses and other educational opportunities in Biomedical Sciences to students at each institution. As part of that initiative, PCOM and Wistar recently received grant funding from VentureWell to support bioentrepreneurship training. The program, culminating in a “Shark Tank” style event at Wistar, is designed to promote the training of underrepresented, developing scientists to pursue careers in the biotechnology industry and/or participate in the technology transfer process that facilitates bringing innovations to the bedside and market.

Media Contacts:

Daniel McCunney
Associate Director, News & Media Relations
Philadelphia College of Osteopathic Medicine
267-449-1360
danielmc1@pcom.edu

Darien Sutton
Director of Media Relations, Communications & Marketing
The Wistar Institute
dsutton@wistar.org

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About Philadelphia College of Osteopathic Medicine
For the past 125 years, Philadelphia College of Osteopathic Medicine (PCOM) has trained thousands of highly competent, caring physicians, health practitioners and behavioral scientists who practice a “whole person” approach to care—treating people, not just symptoms. PCOM, a private, not-for-profit accredited institution of higher education, operates three campuses (PCOM, PCOM Georgia and PCOM South Georgia) and offers doctoral degrees in clinical psychology, educational psychology, osteopathic medicine, pharmacy, physical therapy, and school psychology. The college also offers graduate degrees in applied behavior analysis, applied positive psychology, biomedical sciences, forensic medicine, medical laboratory science, mental health counseling, physician assistant studies, and school psychology. PCOM students learn the importance of health promotion, research, education and service to the community. Through its community-based Healthcare Centers, PCOM provides care to medically underserved populations. For more information, visit pcom.edu or call 215-871-6100.

About The Wistar Institute
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 culture of biomedical collaboration and innovation. Wistar scientists are focused on solving some of the world’s most challenging and important problems in the field of cancer, infectious disease, and immunology. Wistar has been producing groundbreaking advances in world health for more than a century, consistent with its legacy of leadership in biomedical research and a track record of life-saving contributions in immunology and cell biology. wistar.org.

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