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Author: The Wistar Institute

Wistar Institute HIV Researcher Wins Two Grants to Explore Using CAR T Cells as HIV Therapy

Dr. Daniel Claiborne of The Wistar Institute was recently awarded two grants to support studying an approach to optimize CAR T cells, a type of engineered cell, for use against HIV. Claiborne, a Caspar Wistar Fellow in Wistar’s Vaccine & Immunotherapy Center, received a Target Grant for $120,000 from amfAR, The Foundation for AIDS Research, and was also awarded a $65,000 grant from The Campbell Foundation.

The grants will enable Dr. Claiborne to engineer a panel of CAR T cells targeting non-traditional portions of the HIV viral envelope, or outer protein, and test them in a mouse model.

CAR T cells, or chimeric antigen receptor T cells, are patient-derived T cells that have been engineered to target and destroy a specific antigen on the surface of a cancer cell. They are considered “super charged” immune cells that act like a living drug, latching onto a tumor cell to terminate it. CAR T cells have been developed as an immunotherapy for cancer, but Dr. Claiborne explores their potential against HIV.

“My research has focused specifically on identifying the hurdles in repurposing CAR T cells for HIV, and how we can overcome those hurdles to develop an effective treatment,” explained Claiborne. “These grants will enable us to continue working toward that goal, test the approach, and uncover how we can use CAR T cells to develop a successful HIV therapy.”

Dr. Claiborne joined Wistar as a Caspar Wistar Fellow in 2021 from the Ragon Institute of MGH, MIT and Harvard, where he focused his work on better understanding T cells and CAR T cells for the treatment of HIV.

Launched in 2019, The Caspar Wistar Fellows Program is designed to offer exceptional autonomy and resources to recent Ph.D. or M.D. graduates with outstanding research records, who are prepared to take an accelerated path toward independence as principal investigators and join the next generation of scientific leaders.
Caspar Wistar Fellows are appointed for a three-year term with the possibility of extending or being considered for promotion. The Program enables scientists to quickly outfit their lab by offering start-up funds to purchase materials, hire laboratory staff, and access the state-of-the-art shared resources at the Institute.

About amfAR

amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and advocacy. Since 1985, amfAR has invested more than $635 million in its programs and has awarded more than 3,500 grants to research teams worldwide.

About The Campbell Foundation

The Campbell Foundation was established in 1995 by the late Richard Campbell Zahn as a private, independent, nonprofit foundation dedicated to supporting clinical, laboratory-based research into the prevention and treatment of HIV/AIDS. It focuses its funding on supporting alternative, nontraditional avenues of research. The Campbell Foundation has given away more than $12 million since its inception.

Wistar Trainees Celebrate Postdoc Appreciation Week with Trivia Showdown

See if you can beat the winning team at the end of the article!

The air is electric with excitement and trepidation. Ph.D. students, research assistants, and postdoctoral fellows alike have gathered in The Wistar’s Grossman Auditorium for one of the year’s most anticipated scholarly summits: The Wistar Institute Postdoc Appreciation Week Trivia Extravaganza. 

Every year, the Wistar Trainee Association — currently led by Dr. Brennah Britten and doctoral candidate S.K. Reiser — celebrates Postdoc Appreciation Week, an opportunity to spotlight the contributions of postdocs to their labs. Because principal investigators (known more commonly as PIs) spend most of their time planning and managing the work of their laboratories, a good deal of on-the-ground science is led by postdoctoral fellows: Ph.D.-bearing scientists on the road to becoming PIs themselves. In the words of Wistar PI Daniel Claiborne, “By the time you’re a postdoc, you’re a scientific machine: from executing experiments to analyzing data to writing papers, you can (and do) do all the steps of producing research.”

But today, lab coats and nitrile gloves have been set aside in favor of raw determination. “We’re feeling all righty,” said one trivia team (team name: All Righty). “Oh, we’re very confident,” said another team, who’d named themselves, “The [Redacted Name of a Popular Burger Restaurant] Haters” — so-called because they had successfully lobbied for a trivia luncheon of Mexican food in lieu of hamburgers. 

Contestants weathered four rounds: general science trivia; Wistar-specific trivia; a picture round requiring the recognition of esoteric scientific instruments; and Philadelphia trivia provided by one trivia-enthused Wistar PI. 

S.K. Reiser and doctoral candidate Ilan Kirkel alternated as hosts, each holding court with merciless adherence to the competition’s rigor. “You either get full marks — or nothing!” said Ilan when asking which two elements were liquid at room temperature. 

The competition kept a brisk pace, only pausing when Dr. Jason Diaz , education director in the Hubert J.P. Schoemaker Education and Training Center, interrupted to lament  everyone’s missing an easy question in the Wistar trivia round. “If you’ve ever passed our office, you should have known whose ashes are kept here — I’m very disappointed!” 

After a whirlwind three-way race between the top teams — [Redacted Burger Restaurant] Haters, Shine, and D&D — the final winner-take-all event was revealed: a Wistar yo-yo competition, with authentic Wistar-branded yo-yos. Dr. David Stieg of the [Burger] Haters faced off in the dramatic finale against Dr. Brennah Britten of Shine. But after Dr. Stieg walked the dog, catted the cradle and generally wowed the room with his yo-yo prowess, the winner became clear.

The winners went home with Wistar goodies, a sense of accomplishment, and 23 points to their name — plus the satisfaction of having enjoyed their preferred lunch.

Can you beat the winning Wistar trainees? Test your knowledge below!

For each correct answer, award yourself one point. The photo round is not included:; to test your score against the winning team, add 5 points to your total, which is what the winning team scored in the photo round.

QUESTIONS

Round One: General Science

  • What is the average lifecycle of a red blood cell?
  • Which two elements on the periodic table are liquids at room temperature?
  • At what temperature are Celsius and Fahrenheit equal?
  • What does LASER stand for?
  • How many bones do sharks have in their bodies?
  • What is the only planet that spins clockwise?
  • What instrument is used to measure wind speed?
  • What is the smallest named interval of time?

Round Two: Wistar History

  • Who founded The Wistar Institute?
  • When was The Wistar Institute founded?
  • Who was the first female scientist at Wistar?
  • How many PIs are there at Wistar?
  • What was the first vaccine developed at Wistar?
  • Whom is the tower at Wistar named after?
  • Which cytokine was discovered at Wistar?
  • Whose ashes are kept at the Wistar Institute?

Final Round: Philadelphia Trivia, Courtesy of a Generous Wistar PI

  • When it opened in 1874, which family attraction —the first of its kind in America—charged visitors 25 cents to enter?
  • Philadelphia’s border with New Jersey is created entirely by what river?
  • A historic street in Philadelphia, with 32 houses built between 1703 and 1836, is called what?
  • What museum at the College of Physicians of Philadelphia contains historical anatomical specimens, wax models, and antique medical equipment?
  • What dialect, primarily spoken by Mennonites and Amish, is spoken by over 300,000 people and is named as a combination of where it was developed and the language it is a dialect of?
  • Identify the following pattern: 40 37 36 33 30 22 19
  • In 1775 Philadelphia, John Behrent built the first American version of what instrument?
  • A statue of whom sits at the top of Philadelphia city hall?

Bonus: Identify the following Wistar PI:

  • “This PI has grandparents born in Ecuador, Ireland and Spain.  They are the first in their family to graduate college, and their favorite movie is The Warriors.”

ANSWERS

Round One: General Science

  • What is the average lifecycle of a red blood cell? 120 days
  • Which two elements on the periodic table are liquids at room temperature? Mercury and bromine
  • At what temperature are Celsius and Fahrenheit equal? Negative 40
  • What does LASER stand for? Light Amplification by Stimulated Emission of Radiation
  • How many bones do sharks have in their bodies? Zero (sharks only have cartilage)
  • What is the only planet that spins clockwise? Venus
  • What instrument is used to measure wind speed? Anemometer
  • What is the smallest named interval of time? The Planck Time/Duration/Interval

Round Two: Wistar History

  • Who founded The Wistar Institute? General Isaac Jones Wistar
  • When was The Wistar Institute founded? 1892
  • Who was the first female scientist at Wistar? Helen Dean King
  • How many PIs are there at Wistar? 34 (33 also acceptable)
  • What was the first vaccine developed at Wistar? Rubella (rabies also acceptable)
  • Who is the tower named after? Robert and Penny Fox
  • Which cytokine was discovered at Wistar? Interleukin-12 (IL-12)
  • Whose ashes are kept at the Wistar Institute? Isaac Wistar’s

Final Round: Philadelphia Trivia, Courtesy of a Generous Wistar PI

  • When it opened in 1874, which family attraction —the first of its kind in America—charged visitors 25 cents to enter? The Philadelphia Zoo
  • Philadelphia’s border with New Jersey is created entirely by what river? The Delaware River
  • A historic street in Philadelphia, with 32 houses built between 1703 and 1836, is called what? Elfreth’s Alley
  • What museum at the College of Physicians of Philadelphia contains historical anatomical specimens, wax models, and antique medical equipment? The Mütter Museum
  • What dialect, primarily spoken by Mennonites and Amish, is spoken by over 300,000 people and is named as a combination of where it was developed and the language it is a dialect of? Pennsylvania Dutch/German
  • Identify the following pattern: 40 37 36 33 30 22 19 SEPTA Trolley Lines
  • In 1775 Philadelphia, John Behrent built the first American version of what instrument? Piano
  • A statue of whom sits at the top of Philadelphia city hall? William Penn

Bonus: Identify the following Wistar PI:

  • “This PI has grandparents born in Ecuador, Ireland and Spain.  They are the first in their family to graduate college, and their favorite movie is The Warriors.” Dr. Maureen Murphy

Wistar Salutes Celebrates Hispanic Heritage Month

“If you want to make sure that you’re creative and innovative, you need to have a big table and people at it with a lot of different perspectives,” said Marie A. Bernard, M.D., NIH Chief Officer for Scientific Diversity, during Wistar’s Diversity in Science Series. “Traditionally, science academia has been very pyramidal, you get to the peak where there’s only a small number of people, but you need those other perspectives. If you don’t have those diverse minds at the table, you’re missing out on talent. If we are going to maintain our leadership role in biomedical research across the globe, we need to take advantage of all that talent.”

In honor of Hispanic Heritage Month, we are sharing the narratives, perspectives, and points of view of five dynamic scientists living in Philadelphia with cultural roots in South America and Spain. Angela Rios Angula (in the Chen lab), Segundo Del Aguila (in the Villanueva lab) and Rocio Inga (in the Villanueva lab) are from Peru. Marta Tarquis Medina (in the Escolano lab) is from Spain. And Maria Belen Palacio (in the Escolano lab) is from Argentina.

Together, they discussed the initial spark that put them on a path to science; the journey of building community and dynamic careers; and connecting with others through celebrating the vast and varied experiences of Hispanic people from different backgrounds.

Snapshots of the Beginning Scientist

Segundo Del Aguila: My high school biology teacher was a scientist. What I mean is she thought and asked questions like a scientist—she was pragmatic. I liked the way she thought about and viewed everyday problems, but especially how she arrived at the ideal question that got to the heart of a problem. She was a biologist, and because of my interest in understanding life, I decided to take that route too.

In Peru’s capital city of Lima, I knew of three big universities that had biology programs, and I managed to get a scholarship to the best one in research—Cayetano Heredia Peruvian University. I remember that, during the application process, you could write down five different career tracks, but I put only one: biology. The academic advisor told me I had blank spaces and should fill out more, but I knew it was only biology for me.

Angela Rios Angula: When I was young, I was very shy but also very curious. Plants made me wonder how, why and where do they grow? That led me to understand how bacteria survive, and that led me to the human body. Because of this curiosity and passion, I decided to become a scientist; I knew I was not going to give up on whatever I started.

Rocio Inga: I’m from the same university as Angela and Segundo. Our university has only biomedical careers, so it’s very specialized. It is connected to a big hospital and other biomedical research institutes, so we could start learning in the lab early on, within a nurturing scientific environment.
I too was curious as a kid—always looking at bugs and plants and wondering about how they work. My father is a chemical engineer, and he told me about biochemistry as a career, and I’m glad I followed his advice. While taking courses at the university, it was the molecular biology course that really made me passionate. I’ve been fortunate to have many different science career experiences; I’ve worked many years on the molecular biology of Leishmania parasites, worked with cancer cells, worked at different research institutes, and taught at university.

Marta Tarquis Medina: I was super interested in medicine and health care when I was young but knew being a doctor was stressful and demanding. My school had a mini laboratory and good mentors, and I realized I liked being in a laboratory and could have a career in science. I got my bachelor’s degree in biology, left Spain to get my master’s in Germany, and left Germany with a Ph.D. in diabetes.

Belen Palacio: My journey doesn’t go back that far. My high school principal invited a German friend to give a talk about his chemical engineering career working in nanomaterials. I asked what I needed to study to obtain a similar career. But in college, I didn’t like chemistry much, but I did like biology. I tracked into biotechnology and pursued a Ph.D. in developmental biology.

When I was looking for a postdoctoral fellow position, I knew one thing for sure: I wanted my work to mean something to society. I don’t research for the pleasure of research. There must be a greater purpose.

Finding Community

Rocio: We don’t celebrate specific themes, but we celebrate together. We watched the World Cup, we celebrated Peruvian Independence on July 28. We connect over lunch and coffee. We bring back sweets and desserts from our trips home to share with everyone in the lab.

Belen: I’m very family-oriented, so it’s been hard for me. I came abroad and left my whole family in Argentina. The first few months were shocking because I missed my family, my friends and my routine. So, being new to the U.S. and Philadelphia, you must find a new routine. You go out and try to find your people, but you need to build a new community.

Marta: A new scientist comes to Wistar and we ask them, “Do you speak Spanish? Come meet us.” Then Rocio gathers us all together! Rocio, you bring everyone together.

Rocio: Yes, I always liked to gather people together especially those who have recently arrived at Wistar. It’s a chance for them to meet and make new friends. And if they need help with anything, we can help.

Biomedical Role Models

Belen: I didn’t have a role model during my Ph.D. When I came to Wistar and met Amelia, I was stunned how a person can influence your science so much and how they can help you become a better scientist. In Germany during my postdoctoral training, my PI wasn’t around much, and it seemed like I was just carrying out tasks. I had completely lost my passion and almost gave up on science. Then I came to Wistar, and Amelia showed me a new and completely different science panorama. She is encouraging at every step and pushes you in a positive way to become your best version.

Segundo: Jessie is a great mentor. She is my role model, and I am on a similar path to science as she was. We came to the U.S. after studying at the same university. She started as a research assistant and then applied for a Ph.D. program, which is exactly what I’m planning to do. Even though I don’t have a Ph.D., I’m trying to learn and mature as a student would in a Ph.D. program. I will try to be an inspiration for others starting out in scientific careers.

Diversity Matters

Belen: For the next generation of Hispanic scientists, they need to build the foundations of their scientific path. I ended up in immunology, but I didn’t study immunology. When I was getting my Ph.D., I had to learn why I was doing each experiment because if something went wrong, you had to fix it. I knew exactly what each product was and each step in an experiment. I made things from scratch. In my lab, it was not an option to buy a kit or fancy equipment. Here in the U.S., you can buy a kit and in four days you have the result, but do you understand what each step means to your sample or to what you’re doing?

Marta: Regarding science funding in Spain, it’s my view that we must learn to solve problems in a different way. We must think outside the box because we may not have the money to buy the equipment or supplies for an experiment. So we must get to the same conclusion, through a different approach. I think people that come from poorer countries have an out-of-the-box thinking that enriches the lab.

Belen: Try doing science in a developing country. There are many things scientists in the U.S. take for granted because of the technology here. For example, it would take me a year to get an antibody from the U.S. to arrive to Argentina because of customs. This forces us to fully understand the methods of an experiment. In my lab in Argentina, if something doesn’t work, you can’t get a new one or try it again. When you don’t have extra funds, you really think deeply about the protocols and how you will conduct an experiment. You only have one try. Make sure you can accomplish what is important.

Rocio: It’s good to have scientists from different backgrounds, with different ways of seeing things, using different approaches in science. I think that’s the beauty of science: to come together from differences and approach the same problem. And even the youngest people in the lab may think they can’t contribute yet, but even their questions and ideas help to solve a scientific problem.

Wistar President and CEO Dario Altieri, M.D., honored by Justinian Society of Philadelphia for Civic Engagement and Leadership

Dario C. Altieri, M.D., president and chief executive officer of The Wistar Institute will be honored by the Justinian Foundation and Society of Philadelphia for exemplifying the finest qualities of scholarship, civic leadership and integrity.

The Justinian Society, an organization of attorneys, judges and law students of Italian-ancestry who promote continuing education in law and uphold a positive image of Italian-Americans, will recognize the Wistar leader at their annual scholarship reception and luncheon Tuesday, Oct. 10 at the Union League in Philadelphia.

Wistar is the nation’s first independent life science research organization and a global leader in collaborative biomedical breakthroughs leading to the development of novel therapies and vaccines. Through its Hubert J.P. Shoemaker Education and Training Center, top Wistar faculty collaborate with industry experts to advance a well-trained, sustainable life science workforce with programs ranging from pre-apprenticeships through postdoctoral fellowships.

“Just as the Justinian Society has a long-standing history supporting the education of the next generation of legal scholars in our community, at Wistar, we recognize that it is in preparing a diverse and inclusive talent pipeline that today’s discoveries will lead to tomorrow’s cures,” said Dr. Altieri. “I am deeply honored to be recognized by this esteemed Italian-American society committed to advancing professional, academic, civic and cultural excellence here in Philadelphia for the greater good of our global community.”

As president of The Wistar Institute since 2015, Dr. Altieri’s extensive experience working alongside academic, federal, local government, pharma and key life science stakeholders has helped shape the culture of biotechnology in Philadelphia. Wistar now ranks among the nation’s top three drivers of innovation, research and tech transfer, and in the top percentiles for both innovation and research among leading academic and research-related institutions.

Born and educated in Milan, Italy, Dr. Altieri joins past Justinian Italian-American honorees Paul Tufano, general counsel of the Commonwealth of Pennsylvania’s Governor Tom Ridge 1995–1999; Samuel A. Alito, associate justice of the Supreme Court of the United States, and Antonin Scalia (deceased), former associate justice of the Supreme Court of the United States.

A physician, cancer researcher and executive leader, Dr. Altieri initially joined Wistar in 2010 as the first chief scientific officer and director of its National Cancer Institute (NCI)-designated Cancer Center following faculty appointments at Scripps Clinic and Research Foundation in La Jolla, California; Yale University and the University of Massachusetts. He was appointed chief executive in 2015, and continues to direct what is now the Ellen and Ronald Caplan Cancer Center at The Wistar Institute. He also serves as the Robert and Penny Fox Distinguished Professor in Wistar’s Immunology, Microenvironment and Metastasis Program.

“Cooperation, education and inclusion—three fundamental tenets of the Justinian Society—are as imperative in the life sciences sector as they are in the legal profession,” said Barbara A. Capozzi, president of the Justinian Foundation. “As we celebrate the next generation of legal and judiciary leaders through academic scholarships promoting the principles of good fellowship, maintaining honor and dignity of the legal profession, performing civic duties, administering justice and promoting the study of law, is our distinct privilege to recognize Dr. Altieri as an Italian-American leader to be emulated in our region – and beyond.”

Event details:
For tickets to the Oct. 10 Justinian Society of Philadelphia annual scholarship reception and luncheon at the Union League, contact Joanne Crane Tsucalas at jct.uta@att.net.

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The Wistar Institute, the first independent, nonprofit biomedical research institute in the United States, marshals the talents of an international team of outstanding scientists through a 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.

The Justinian Foundation is a 501(c)3 nonprofit organization founded in 1996. The charitable arm of The Justinian Society (1935), the Foundation’s sole purpose is to provide financial assistance to law students currently enrolled in an accredited law school in a program of study leading to a juris doctor degree. Scholarship candidates must be admitted to an accredited law school within a one hundred (100) mile radius of the City of Philadelphia and must be entering, at a minimum, their second year; or must meet the requirements for specific scholarships. All gifts are tax deductible. In addition to our general scholarships, our two named scholarships include the Jules Fiorvanti Scholarship which is granted to a student at LaSalle University interested in the study of law. The Richard F. Furia, Esquire Scholarship is granted to the winner of an essay contest with a focus on advocating against stereotyping and defamation. www.justinian.org/foundation.php

The Justinian Society is a legal organization comprised of attorneys, judges and law students of Italian-ancestry. Founded in 1925, the Society is located in Philadelphia. The Justinian Society members are engaged in activities directed toward fostering a spirit of good fellowship, maintaining honor and dignity of the legal profession, performing civic duties, administering justice, and promoting the study of law. The Justinian Society promotes continuing education in law, supports the advancement of qualified and distinguished Justinians in public office, serves the Italian-American legal profession and the community, and strives to uphold a positive image and take action against negative stereotyping against Italian-Americans.

EVs Drive Cancer. A Wistar Scientist Wants to Know How

Dr. Irene Bertolini of the Altieri Lab investigates extracellular vesicles and their role in metastasis

When cancer spreads, cancer kills. Cancer’s ability to spread to other parts of the body — a process known as metastasis — makes the disease dangerous and more complicated both for the patient and the medical professionals treating the disease. Decades’ worth of cancer research has investigated the multitude of factors that can drive metastasis.

One of these factors is the presence of extracellular vesicles, or EVs, the research interest of Irene Bertolini., Ph.D., an associate staff scientist in Wistar’s Altieri Lab. Her research shows that EVs from cancer cells can contribute to the conditions that allow cancer to flourish and spread in breast cancer, the second most common cancer in women.

Vesicles are small particles created by cells that contain biological materials. When a vesicle leaves a cell, that vesicle is said to be extra-cellular. Cancerous cells emit EVs just like regular cells, but, being cancerous in origin, breast cancer EVs can carry carcinogenic properties.

Dr. Bertolini investigates the connection between breast cancer EVs and the tumor microenvironment, which can be thought of as the biological garden that cancer grows in. Like garden plants, cancers grow and spread better in certain conditions. Cancer cells work to foster those conditions, and Dr. Bertolini found that EVs produced by hypoxic (oxygen-deficient) breast cancer cells promote a variety of carcinogenic and metastatic conditions.

Using EVs from hypoxic breast cancer cells, Dr. Bertolini found that EVs increase angiogenesis, the process that forms new blood vessels. When new blood vessels form around cancer, the cancer cells use them to siphon more of the body’s nutrients, which allows cancer to grow and potentially metastasize.

Dr. Bertolini’s research also revealed that the EVs showed increased packaging of a protein called HIF1α, which has been linked to a variety of metastatic cancers. And relative to controls, tumor formation & growth in mice treated with cancer-derived EVs was significantly more rapid.

“EVs from cancerous cells basically transmit packets of potent cancer-causing material,” said Bertolini. “Where EVs move, conditions conducive to cancer follow.” Because EVs can move beyond cancerous cells and into healthy tissue, she says, they have the capacity to drive metastasis.

To that end, Dr. Bertolini plans to study the role of hypoxic breast cancer EVs in metastasizing to the liver, specifically. So far, she has found that EVs do indeed migrate to the liver, where she’s observed pro-cancer effects like increased angiogenesis and reduced counts in anti-tumor T-cells.

“Understanding why EVs help cancer spread is the first step in understanding how to stop them,” said Dr. Bertolini. “If we know what they do and how they do it, that’s half the battle.”

Notes from the Field: Dr. Ian Tietjen in Africa, Part 3

Dr. Ian Tietjen is a Research Assistant Professor in Wistar’s Montaner Lab, where he investigates traditional African medicinal compounds’ potential for drug origination against viruses like HIV. Dr. Tietjen travels to Africa to work with traditional healers to better understand the function of these compounds.

If you haven’t started this series with part one, click here.

6 August 2023 – Today we drove to several of the surrounding villages to pick up the healers and take them back to the Shumba Lodge. There were a few groups that went out; my group included Rhona and Jimson Richard as the van driver. Jimson is Richard’s brother and a clerk for the Tutume local government. We went to two villages in the Tutume area, including Mosetse and Maitengwe.

As you can imagine, building trust is essential to establish rapport — which, for me and my colleagues, includes meeting with the family and the leader to discuss how long the elder will be away from the village. We take the time to assure them that we receive no money for these educational sessions and that we always learn as much as is imparted. For this session, we show our healer collaborators how we do biomedical science by running experiments on plant samples. For this visit, we are asking all the healers to refrain from telling us any plant identities and keep all Indigenous or other personal and protected knowledge secret from us.

Our primary goal is to work together to support traditional knowledge with biomedical laboratory resources to better understand natural medicines from many points of view to support healers and their communities. After these meetings, all the families eventually agreed to let the healers go with us; the families even got their photos taken with us. The family’s children are so engaging and fun to talk to.

In total, we have 12 healers from across the region staying with us. There are women and men of all ages: young students just out of university all the way to elders. Some are fluent in English, some know very little, and some know a lot more than they are letting on.

Maitengwe Village
Goats in the Village
Eventually we got all the healers on board and fed everyone dinner in Tutume that evening.

Wistar Researchers Discover Possible New Treatment for Triple-Negative Breast Cancer 

PHILADELPHIA—(Sep. 18, 2023)—Zachary Schug, Ph.D., assistant professor in the Molecular and Cellular Oncogenesis Program of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute, has published a new paper in the journal Nature Cancer. Schug’s paper — titled, “Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer” — demonstrates a double-acting mechanism for fighting a particularly aggressive, difficult-to-treat form of breast cancer. Schug’s research shows how silencing a certain gene, ACSS2, may improve existing treatments for patients.

Triple-negative breast cancer, or TNBC, affects 10-15% of patients with breast cancer in the US. TNBC is called “triple-negative” because the cancer lacks an estrogen receptor, a progesterone receptor, and a HER2 (human epidermal growth factor) receptor. The absence of any of these receptors — receptors that, when present in other forms of breast cancer, can be effectively targeted during treatment — makes treating TNBC quite difficult, and patients with TNBC have limited treatment options. TNBC’s notorious aggression makes the technical challenge of finding a reliably effective treatment target all the more serious: compared to other breast cancers, TNBC grows faster and resists treatment more stubbornly. All these factors contribute to the fact that TNBC patients suffer from worse prognoses.

But Zachary Schug, Ph.D., and co-authors have demonstrated the efficacy of a double-acting concept: silencing the gene ACSS2 impairs TNBC metabolism while simultaneously boosting the immune system’s ability to fight it. ACSS2 regulates acetate, a nutrient that cancer cells — and TNBC cells in particular — take advantage of to grow and spread. Schug and his team used two methods to de-activate ACSS2: CRISPR-Cas9 gene editing, and the compound VY-3-135, a potent ACSS2 inhibitor identified by Schug and his colleagues in 2021.

The researchers found that targeting ACSS2 in this preclinical study not only hampered this aggressive cancer’s ability to metabolize acetate and grow — it also triggered the immune system to recognize and attack the cancer. Because cancer cells with inhibited ACSS2 can’t process acetate very well, the tumor region becomes bathed in acetate, which alerts the immune system of something amiss.

This process of guiding the immune system to the cancer — called “immunosensitization” — has confounded other TNBC researchers. But Schug’s approach showed that ACSS2 inhibition immunosensitized against TNBC so well that tumor growth was drastically reduced, even to the point of wiping out the cancer completely in some experiments.

“Basically, we’ve proved that the immune system can take advantage of acetate that the tumor can’t process. It kicks the cancer while it’s down,” said Schug. “In fact, the immune system does this so well that it remembers how to attack TNBC in the future — even if that tumor’s ACSS2 gene is still active.”

Another group’s different ACSS2-inhibiting approach is in human clinical trials, and Schug’s research shows how ACSS2-inhibiting treatment might be able to improve outcomes for patients diagnosed with the infamous TNBC. By testing ACSS2 inhibitors alongside standard anti-breast-cancer chemotherapy, Schug et al. found that ACSS2 inhibition enhanced the treatment’s effectiveness.

“We knew that ACSS2 was a promising target for TNBC. Our research shows us how the immune effects of ACSS2 inhibition could eventually be used in for TNBC patients with limited treatment options,” said Schug. “More research is needed, but by combining this approach with other cancer therapies, we expect to see big improvements in treating TNBC.”

Co-authors: Katelyn D. Miller, Seamus O’Connor, Katherine A. Pniewski, Toshitha Kannan, Reyes Acosta, Gauri Mirji, Sara Papp, Michael Hulse, Fabrizio Bertolazzi, Yellamelli V. V. Srikanth, Rahul S. Shinde, Daniel T. Claiborne, Andrew Kossenkov, Joseph M. Salvino and Zachary T. Schug of The Wistar Institute; Fabrizio Bertolazzi of the University of Bologna; and Steven Zhao and Kathryn E. Wellen of the University of Pennsylvania.

Work supported by: This work was supported by grants from the National Institutes of Health (NIH) National Cancer Institute (NCI) DP2 CA249950-01, NIH NCI P01 CA114046, NIH R21 CA259240-01, the W.W. Smith Charitable Trust, Susan G. Komen CCR19608782 and the V Foundation for Cancer Research. This research and project is funded, in part, by a contract with the Pennsylvania Breast Cancer Coalition. The PBCC takes no part in and is in no way responsible for any analyses, interpretations or conclusions contained herein. We acknowledge funding from the NIH NCI T32 CA009171 and the American Cancer Society Rena and Victor Damone Postdoctoral Fellowship PF-20-1225-01-CCG. The Wistar Molecular Screening Facility and Genomics Facility are supported by NIH grant P30 CA010815. The Wistar Proteomic and Metabolomic Facility is supported, in part, by NIH grants R50 CA221838 and S10OD023586. The HIC is supported, in part, by NIH P30 AI045008 and P30 CA016520.

Publication information: “Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer” from Nature Cancer

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Notes from the Field: Dr. Ian Tietjen in Africa, Part Two

Dr. Ian Tietjen is a Research Assistant Professor in Wistar’s Montaner Lab, where he investigates traditional African medicinal compounds’ potential for drug origination against viruses like HIV. Dr. Tietjen travels to Africa to work with traditional healers to better understand the function of these compounds.

If you haven’t started this series with part one, click here.

5 August 2023 – Our combi bus picked us up from the hotel and briefly stopped at the Gaborone airport to retrieve more of our team. We are here to pick up our guests from British Columbia, Canada who have been travelling for almost 48 hours nonstop: Marianne Ignace, Professor of Linguistics at SFU; Dr. Ron Ignace, a retired Chief of the Secwepemc First Nation of British Columbia; and their son Joe Ignace. With them are two Secwepemc traditional healers, Rhona Bowe and Rod Tomma, who are helping us engage and work with traditional healers.

In total, there are 13 of us. The ride from Gaborone to Tutume is mostly a smooth, paved, two-lane road, but it takes about seven hours of driving. The scenery is flat with lots of short, brambly trees; cows, goats, and donkeys amble up and down the side of the highway, and people are selling food, brooms, and gasoline along the side of the road. The sunset is dusty and orange, and it makes sharp silhouettes of the trees. With the sun setting, our goal is to get to Tutume before dark to avoid the many animals that wander the highway at night.

By the time we reach Tutume, the town and its stores have largely gone to sleep. Our big tour group is staying at the Shumba Lodge, so we are being housed and fed by local Qalose.

Tomorrow we will pick up the healers from their villages across the Tutume district and in Francistown, Botswana’s second largest city, about two hours away. Many people in Botswana rely on more than one medical system for their health: A Western doctor for medicines and treatments, and a community healer for medicines that provide wellness, mental health, and spiritual support. Surprisingly, many people in Botswana do not think highly of this unique knowledge, even though they may use it themselves or have practicing healers in their family.

In my experience, traditional healers have spent years learning about medicinal plants and their uses. When speaking to them, they often sound like pharmacists or scientists, and they use scientific and hypothesis-driven methods to understand and improve their plants. In addition to studying these plants, we want to help validate their uniqueness. If biomedical scientists and healers can combine their respective knowledge and work together constructively, I really believe we will discover new ways to improve health and wellness that are not being considered today.

This is a typical business street in Tutume, although there are also modern strip malls and supermarkets as well.
This is the Shumba Lodge, where we had several peacock and cats as companions.

Research and Rackets

For Wistar’s Pratik Bhojnagarwala, the game of squash keeps him focused on his research.

During most days of the week, you can find post-doctoral trainee Pratik Bhojnagarwala in the Weiner lab, performing research projects at the bench or scouring results to determine where his findings may lead. Or, as the Vice President of Fundraising and Partnerships for Wistar’s Trainee Association, he might be coordinating activities and events for Wistar’s training programs, helping students get the most out of their experience at Wistar.

The work can be intense, with countless hours spent reviewing data, designing experiments, or reading up on the latest papers to track findings by other scientists.

“There might be weeks after I’ve finished 10 experiments, then I need to analyze all the data. The next steps are to figure out what I need to do to move the project forward. Some days I’m heavily focused at the bench, and other days I’m at my desk analyzing data.”

But if you’re hoping to find Pratik Monday or Thursday evenings, don’t bother looking in any Wistar lab. He’ll be farther afield, focused not on cancer cells but on the path of a small, rubber ball.

He’ll be sweating it out on a squash court.

“It’s almost religious for me. I arrange my schedule trying to make sure I can play each week,” Bhojnagarwala says of his squash routine. “I have a group of people that I’ve been playing with for over 10 years at this point. It’s not just physical exercise, it’s also a social gathering. I really try and make it mandatory.”

For those in the know, Philadelphia is a squash mecca. The sport’s overseeing body, U.S. Squash, was founded in the city in 1904. Then, in 2020, the city converted an old armory on Market St, adjacent to Drexel’s campus, turning it into the Arlen Specter U.S. Squash Center, a 40,000 square foot facility that further elevated Philadelphia’s prestige in the squash world.

These days, Pratik meets up with friends at the nearby Drexel University squash courts for his weekly sessions.

Pratik’s path to squash started during graduate studies at Penn, when a few classmates invited him to join their matches. Over time he, too, picked up the sport, and it became an integral part of his weekly routine.

The court offers a much-needed respite from his day job, burning off energy and clearing his head. “I try not to miss anything that helps with my physical fitness, relaxation and gets me out of the lab,” Pratik explains. “I play with a group of people from very different walks of life — not everybody is in science. So just getting to talk to those people and learning from them — it’s a good way to disconnect. And it’s been very rewarding.”

In some ways, squash offers a parallel to what Pratik does in the lab. He might follow a path, take it wherever it leads, and then pivot based on what he finds. There’s a cadence to both, and a need to think on your feet and react to unexpected results: in squash, a strange bounce can suddenly send the ball straight at your head, while in the lab a set of results may change the trajectory of your research plan.

For Pratik, this is all part of the journey.

After receiving his master’s degree, he spent several years as a research technician at Penn before moving on to his Ph.D. work. “It was not the most traditional career path because I got into grad school later on,” he explains. “I … spent almost six years as a research technician at Penn before I had to go to grad school.”

The experience, however, is something that he values and would recommend to others. “I would definitely advise people to take a year or two after their undergrad or masters, work in a lab and … figure out if that is something they even want to do.”

In fact, Pratik recently defended his thesis and attributes that lab experience, in part, to the successful outcome. “Leading up to where I got on the stage was nerve wracking, but once I was there it felt very natural. I think it was because of the five years that spent in the lab, especially in the Wistar lab. We make full presentations during lab meetings, so it helped my confidence.”

But behind all his academic success and commitment is a simple rule: Pratik firmly believes in outside activities to clear your head and rejuvenate your soul. “It’s very important to find time … to disconnect and switch off, just go out there and do other things.”

Notes from the Field: Dr. Ian Tietjen in Africa, Part One

Dr. Ian Tietjen is a Research Assistant Professor in Wistar’s Montaner Lab, where he investigates traditional African medicinal compounds’ potential for drug origination against viruses like HIV. Dr. Tietjen travels to Africa to work with traditional healers to better understand the function of these compounds.

3 August 2023 – Today we are in Gaborone, the capital city of Botswana in Southern Africa, to prepare for a biomedical workshop that we are planning to hold next week in Tutume. Tutume is the main town of the Tutume district in Northeast Botswana, and Dr. Khumoekae Richard, a postdoc in Dr. Luis Montaner’s lab, and I began engaging with traditional healers back in 2019. We have been interested in working in Tutume because it has a large, complex traditional medicine system in addition to the Western medical system that we are more familiar with. However, in Tutume, the medicinal plant preparations and uses to manage HIV/AIDS, COVID-19, cancer, hypertension, and other diseases, are relatively undocumented. 

We want to understand how healers identify and use local medicinal plants and how they may work at the molecular and cellular levels. Importantly, we also want to engage with the communities in a way that creates a trusting, open dialogue. For example, it is essential that we do not simply “take the medicines, make money, and never return.” Instead, we need to find new ways to work with healers over the long term so that their indigenous knowledge directly and primarily leads to local advances and benefits for both healers and their communities. We hope this workshop will be a first step toward achieving this.

Richard is originally from Botswana and grew up near Tutume, so he is fluent in the local languages (Setswana and I-Kalanga) and knows all the local customs and nuances. Since 2019, local Tutume healers have been particularly welcoming and open to working with him. From 2020-2022, Richard was fortunate to interview 13 healers from the region and document the medicinal plants they use to treat local people and their ailments. We focused on plants used for HIV, but they provided information on many others. 

Richard collected 196 plants, of which 83 were bio-authenticated by a botanist at the University of Botswana. We just published the first manuscript in June 2023 (PMID: 37301306), but now it is time to meet the healers in-person and find ways to move this collaboration forward together. 

For this visit, we showed healers and the local Tutume community some of the biomedical laboratory techniques that we typically use. We invited healers to bring plant samples to the workshop without disclosing their identities, and we will attempt to make extracts and test them for various bioactivities. We hope this workshop will help demystify scientists and hopefully jump-start new discussions of what we can do together. Richard and I are learning how to do this workshop under the guidance of Prof. Kerstin Andrae-Marobela at the University of Botswana, who has pioneered this approach in other parts of Botswana and elsewhere. We will soon be joined by researchers and knowledge-keepers from Canada and South Africa as well. 

Today Richard and I had the opportunity to meet with the Honourable Dr. Douglas Letsholathebe, the Minister of Education and Skills Development of Botswana. He was formerly a physics professor at the University of Botswana and has a keen interest in incorporating local indigenous knowledge systems into Botswana’s economy to strengthen local knowledge, education, and natural resources. He is a good ally for work like this, and we hope we can be a good ally for him. 

Richard also took us to Re Ja Sets, a traditional hut outside of Gaborone that cooks traditional Setswana food. Setswana food is simple and elegant at the same time — the traditional dish is usually beef or chicken on top of pap (milled corn), sorghum and pumpkin, or millet, with cabbage and maybe some spicy pepper sauce. Unlike most meat in the United States, Botswana’s protein has been free to spend its life running around and foraging; it also gets cooked right away. As a result, the flavor and texture are unlike anything we can get in a supermarket or restaurant in the West. The whole meal is very social: we sit in the hut and talk cordially with everyone around us, including the local farmers and restaurant owner. Everyone eats with their hands, but somehow, I seem to just make a mess instead. 

Meeting and discussing Indigenous community and healer engagement projects with the Honourable Dr. Douglas Letsholathebe, Minister of Education and Skills Development of Botswana (second from left), far left is Dr. Khumoekae Richard, second from right is Dr. Ian Tietjen, and far right is Prof. Kerstin Andrae-Marobela.

Best dinner ever! (At least so far!)