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Wistar President Dario Altieri, M.D., recognized as one of Philadelphia’s Most Admired CEOs

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

PHILADELPHIA—(Dec. 4, 2023) — Dario C. Altieri, M.D. — The Wistar Institute’s president and CEO, director of its Ellen and Ronald Caplan Cancer Center and the Robert & Penny Fox Distinguished Professor — is a recipient of the 2023 Most Admired CEO Awards recognized by the Philadelphia Business Journal for his leadership and service to Wistar.

The Most Admired CEO Award is given to recognize select leaders from the Greater Philadelphia area “who have earned respect from within and outside their companies and are leaving a mark on Greater Philadelphia and beyond.” Dr. Altieri and fellow awardees are being honored with a special December edition of the Philadelphia Business Journal commemorating their achievements and a celebration at the Switch House in Philadelphia.

“I’m honored and delighted to receive this award,” said Dr. Altieri. “I’ve had the privilege to lead The Wistar Institute for eight years now, and I continue to be inspired by all the people I have the privilege to work with at Wistar. To be recognized this way is truly a great personal and professional honor.”

Since 2015 Dr. Altieri has served as Wistar’s President and CEO while continuing to run both the NCI-designated Ellen and Ronald Caplan Cancer Center at Wistar and his research laboratory —which investigates the role of mitochondria in cancer and is recognized for having discovered the survivin gene, a fundamental cancer gene. Under his leadership, The Wistar Institute has continued to steadily grow for research impact and innovation, development of a diverse and well-trained workforce, and creation of an inclusive ecosystem for the life sciences in our region.

“Dario’s leadership has taken Wistar to new heights,” said Maureen Murphy, M.D., deputy director of the Ellen and Ronald Caplan Cancer Center and Ira Brind Professor and program leader of Wistar’s Molecular & Cellular Oncogenesis Program. “I speak for all the faculty here when I say that we’re lucky to have such a stellar leader.”

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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.

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

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

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.

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

Wistar Scientists Identify Link Between Mitochondria and Pancreatic Cancer Risk

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Fighting Breast Cancer Disparities Through Collaboration

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

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

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

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

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

RESEARCHING TRIPLE-NEGATIVE BREAST CANCER

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

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

ALCOHOL AND BREAST CANCER

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

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

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

GENETICS AND ALCOHOL METABOLISM

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

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

ALCOHOL-RELATED ENVIRONMENTS AND BEHAVIORS

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

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

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

THE RESEARCH PROJECT

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

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

IMPACTING PATIENTS, PROVIDERS, AND COMMUNITIES

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

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

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

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

A LASTING COLLABORATION

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

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

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

SOURCES

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

Taking on Cancer

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

Philadelphia Business Journal senior health reporter John George hosted Taking on Cancer, a two-panel discussion that kicked off with perspectives from local research leaders at the helm of world-class research institutes and health care systems. It was followed by the innovative go-getters behind health care startups in the region. The intimate event took place in the high ceiling, music venue City Winery in Philadelphia’s Center City.

Leaders sat shoulder to shoulder to discuss the challenges and changes to cancer research and patient care. The first panel gave perspectives on what the future holds for the region and included Dr. Dario Altieri, Wistar Institute president & CEO, director of the Ellen and Ronald Caplan Caner Center, and the Robert and Penny Distinguished Professor; Dr. Generosa Grana, MD Anderson Cancer Center at Cooper director; Dr. Jonathan Chernoff, Fox Chase Cancer Center director; Dr. Andy Chapman, Jefferson Health’s Sidney Kimmel Cancer Center director; and Dr. Robert Vonderheide, University of Pennsylvania’s Abramson Cancer Center director.

Dr. Altieri represented the panel’s lone basic cancer research center and brought a high-level drug discovery perspective to what John George coined Philadelphia—an “epicenter for cancer research”. Dr. Altieri stated, “We’ve gotten better at public-private partnerships, and we’ve greatly improved the dynamics related to drug discovery and development. We’ve been exploring more and are doing a better job advancing promising new assets, so we are seeing a higher number of success stories.”

The other leaders, representing comprehensive cancer centers that treat patients and conduct research, felt the same – that the last 20 years of cancer research has been a sort of science revolution in our understanding of how genes act together and the hopes of altering or editing them, how to identify and predict cancer risk, and how to treat immune system pathways that were once thought undruggable with emerging drug candidates. In the process, Philadelphia has become central to cell and gene therapy and referenced as “Cellicon Valley”. The region now also supports a teeming cell and gene therapy ecosystem backed by a workforce that understands bioprocessing this “living drug”.

Together, the panel agreed that Philadelphia is poised to be a leading city in the battle against cancer—all due to the innovation of academic institutes coupled with innovative business investment and supporting infrastructure, and the ability to provide delocalized, multidisciplinary care to cancer patients.

As we continue shaping and building this life science ecosystem, Dr. Altieri remarked on the day-to-day challenges of cancer research and what’s to come. “At times, things may not seem to move fast enough, and our work seems incremental, taking only small steps forward. However even those count, as we move away from dogma and assumptions and from the mindset that there are undruggable targets. Discovery through innovation will become more adventurous.”

Dr. Dario Altieri smiles in a Wistar lab

Wistar Scientists Identify Therapeutic Target for Metastatic Cancers

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

Damaged “ghost” mitochondria are found to drive tumor progression.

Metastasis, or the spread of cancer from one place in the body to another, is responsible for more than 90% of all cancer deaths. Therefore, determining how and why this happens is an important part of cancer research. A new collaborative study led by scientists at The Wistar Institute identified one such mechanism thanks to “ghost” mitochondria.

Because they are the “powerhouse” of the cell, mitochondria (a specific organelle inside human cells) are crucial for cell survival, including tumor cells. However, recent research has shown that mitochondria in many human tumors lack an important protein called Mic60. Normally missing a crucial protein is a recipe for disaster, yet these mitochondria and their cells survive.

To determine how this is possible and how it affects tumor cell behavior, Dario C. Altieri, M.D., Wistar president and CEO, director of The Wistar Institute Cancer Center, and the Robert & Penny Fox Distinguished Professor, led a team of researchers in reproducing these types of low-Mic60 tumor cells in mice to enable closer examination. In doing so, they found two things. First, in cells where Mic60 was depleted, all of the mitochondria’s structures and functions were damaged or inhibited.

“They really didn’t produce any energy, which is what mitochondria do,” said Altieri. “That was the idea of calling them ‘ghosts’—because in essence the mitochondria were still there, but they didn’t do anything, or anything good, at least.”

Second, the scientists found that while inferior organelles are usually removed from healthy cells via a quality control process, the ghost mitochondria were not removed from tumor cells. Not only were they not removed, but they helped the cell metastasize.

Given these findings, the scientists speculate that the low-Mic60 tumor cells activate two pathways to stay alive: Akt (related to survival) and GCN2 (related to stress response). Drugs interfering with these pathways could, therefore, help to stop metastasis and kill the cancer.

“The idea would be to eliminate the adaptive responses that these Mic60-low tumors mount to remain alive and viable through a combination targeting of Akt and GCN2,” said Altieri.

The Wistar Institute building

The Wistar Institute Hosts U.S. Department of Commerce Official Making Major Grant Announcements to Strengthen Workforce Pipelines in Philadelphia & Across the Nation

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

Wistar is a finalist of the STEM Talent Challenge to create a new life science workforce training program to address Pennsylvania industry growth and demand for skilled workers.

U.S. Assistant Secretary of Commerce for Economic Development Alejandra Y. Castillo will make a major national grant announcement in support of locally-driven programs that train STEM-capable workforces across the country and create pathways for good-paying STEM jobs in Philadelphia and across the United States at an event on Thursday, January 27, 2022 in Philadelphia.

WHO:

  • Ms. Alejandra Y. Castillo
    U.S. Assistant Secretary of Commerce for Economic Development
    U.S. Department of Commerce
  • Ms. Mary Gay Scanlon
    U.S. Congresswoman
    Pennsylvania’s 5th District
  • Mr. Jim Kenney
    Mayor
    City of Philadelphia
  • Dr. Dario Altieri
    President & CEO
    The Wistar Institute


WHAT: Major grant announcement in support of locally-driven efforts to strengthen innovation workforce pipelines in Philadelphia and across the United States.

WHEN: Thursday, January 27, 2022; 11 a.m./EST

WHERE: The Wistar Institute; Media are welcome to attend and ask questions virtually.

REGISTRATION: Please use the link below to register: https://register.gotowebinar.com/register/9102191982375060492

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.

The mission of the U.S. Economic Development Administration (EDA) is to lead the federal economic development agenda by promoting competitiveness and preparing the nation’s regions for growth and success in the worldwide economy. An agency within the U.S. Department of Commerce, EDA makes investments in economically distressed communities in order to create jobs for U.S. workers, promote American innovation, and accelerate long-term sustainable economic growth. To learn more about EDA, visit www.eda.gov.

Fox Chase Cancer Center, The Wistar Institute Announce Opening of Phase 1 Clinical Trial of Anticancer Drug Candidate

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

PHILADELPHIA — (Dec. 2, 2021) — Fox Chase Cancer Center has opened an investigator-initiated, phase 1 clinical trial to evaluate the safety and efficacy of gamitrinib in patients with advanced cancer. Gamitrinib is a first-in-class, mitochondrial-targeted inhibitor of the molecular chaperone heat shock protein-90 (HSP90) that works by inhibiting tumor cell metabolism and survival.

Gamitrinib was developed at The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease, and vaccine development, and the two Philadelphia institutions are collaborating to bring this potential new therapy to patients.

The study is a single center, open-label, phase 1 clinical trial of weekly intravenous gamitrinib administration. It is designed to enroll 18 to 36 patients. The primary goal of the study is to determine safety and tolerability. It will be complemented by analyses to determine how gamitrinib is metabolized in humans, assess biochemical evidence of target engagement, and gauge early efficacy signals.

Anthony J. Olszanski, MD, RPh, director of the Phase 1 Development Therapeutics Program and vice chair of clinical research at Fox Chase, is the principal investigator on the gamitrinib trial. “We are excited to share the news that the gamitrinib trial is now open for accrual. We hope to make progress in this very first step toward a promising new treatment for patients with advanced cancer, where there remains a high unmet need for new, effective therapies,” said Olszanski.

“Gamitrinib has had a long and storied journey,” said Dario C. Altieri, MD, Wistar president and CEO, director of The Wistar Institute Cancer Center, and the Robert & Penny Fox Distinguished Professor. His laboratory designed and developed the new drug candidate for clinical use.

“It is a humbling moment to see what started as a research tool advance through preclinical development and now reach our patients. From the start, and continuing to this milestone, this project has embodied our nation’s investment in research solely and continuously supported by competitively awarded public funds,” Altieri said.

“This new trial is important on many levels,” said Jonathan Chernoff, MD, PhD, Cancer Center Director at Fox Chase, which is part of the Temple University Health System. “Delivering anticancer agents inside mitochondria has not previously been brought to the clinic in oncology. It is a highly collaborative, longstanding endeavor across cancer centers here in Philadelphia and delivers considerable innovation for a first-in-human, investigator-initiated clinical trial.”

Known as the powerhouses of the cell for their ability to produce large quantities of cellular energy, mitochondria have been recognized as important tumor drivers, sustaining many critical disease traits. This involves a pool of the HSP90 chaperone that selectively accumulates in the mitochondria of tumor cells and helps in the folding and stability of critical mitochondrial proteins exploited in cancer.

Although conventional HSP90 inhibitors previously tested as cancer drugs failed to accumulate in mitochondria, gamitrinib was designed by the Altieri laboratory to selectively localize to mitochondria, inhibit the function of HSP90, and induce the collapse of mitochondrial metabolism and tumor cell survival.

Funding for the phase 1 clinical trial to evaluate the safety of gamitrinib is being provided by the National Institutes of Health’s National Cancer Institute, the U.S. Army Medical Research and Development Command’s Congressionally Directed Medical Research Program, and Gateway for Cancer Research, a nonprofit organization dedicated to funding meaningful breakthrough treatments and cures for patients worldwide.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.

About Fox Chase Cancer Center
The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach. It is the policy of Fox Chase Cancer Center, that no one shall be excluded from or denied the benefits of or participation in the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

Wistar Scientists Unveil Mechanism That Stops Cancer Progression by Interfering With Cancer Cell Metabolism

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

During progression from a precancerous lesion to an aggressive tumor and then metastasis, cancer cells rewire their metabolism to support increased energy demands due to continuous growth and adapt to unfavorable conditions in the surrounding environment.

In a study published in the journal Science Advances, Dr. Altieri and colleagues discovered a new mechanism that suppresses tumor development by interfering with metabolism and with the function of mitochondria, the cell’s powerhouse.

Understanding Parkin

The team studied a gene called Parkin that is known for its protective function in brain cells and is altered in Parkinson’s disease. Previous evidence indicated that Parkin might have a role in regulating cancer cell metabolism and suppressing tumor growth, but the mechanism remained elusive.

The team found that Parkin expression was low or undetectable in tumors compared with their respective normal counterpart.

When they re-introduced Parkin in prostate cancer cells and other cancer cell types that did not express the protein, they observed reduced cell movement and a blocking of invasion, while deletion of Parkin in normal cells increased cell motility.

In vivo, Parkin-expressing prostate cancer cells formed smaller tumors and had lower metastatic potential.

Role of Parkin and Mitochondria

The Altieri lab has contributed important knowledge in the role mitochondria play in cancer, showing that changes in their size, shape and distribution within cells increase their ability to move and invade other tissues and acquire other aggressive traits.

In the new study, they discovered that Parkin interferes with the function of mitochondria in cancer cells, and, as a consequence, blocks tumor cell motility, which is critical for their ability to disseminate and invade other tissues during metastasis.

Forced Parkin expression in cancer cells also resulted in reduced energy production.

In addition, researchers found that exposing Parkin-expressing cancer cells to stress conditions such as nutrient deprivation and DNA-damaging agents resulted in a strong increase in Parkin levels.

From this study, Parkin emerges as a critical, stress-activated effector of a tumor suppression pathway that stops cancer progression and metastasis by interfering with the ability of cancer cells to reprogram their metabolism.

Wistar Science Highlights: New Discoveries on HIV Latency and How Cancer Cells Talk With Their Neighboring Normal Cells

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

Antiretroviral therapy (ART) has dramatically increased the health and life expectancy of HIV-infected individuals, suppressing virus replication in the host immune cells and stopping disease progression; however, low yet persistent amounts of virus remain in the blood and tissues despite therapy. Virus persistency limits immune recovery and is associated with chronic levels of inflammation so that treated HIV-infected individuals have higher risk of developing a number of diseases.

This persistent infection stems from the ability of HIV to hide in a rare population of CD4 T cells. Finding new markers to identify the virus reservoir is of paramount importance to achieve HIV eradication.

The lab of Mohamed Abdel-Mohsen, Ph.D., assistant professor in the Vaccine & Immunotherapy Center, may have discovered a new way of identifying and targeting hidden HIV reservoirs during ART.

The sugar molecules present on the surface of immune cells play a critical role in regulating their functions and fate. Researchers explored the role of the sugar component on the surface of host cells and described a “glycomic — or sugar — signature” that can impact HIV persistence.

Published in Cell Reports, the findings may have translational implications for improving the long-term care of HIV positive people.

The crosstalk between cancer cells and their neighboring normal cells is important to promote cancer progression.

The lab of Dario C. Altieri, M.D., Wistar president and CEO, director of the Institute’s Cancer Center and the Robert & Penny Fox Distinguished Professor, studied how this exchange happens to gain more clues on how tumors “hijack” their microenvironment and promote disease progression and recurrence.

Researchers cultured breast cancer cells in low-oxygen to mimic a condition known as hypoxia, which is a hallmark of the microenvironment surrounding most solid tumors. In this setting, they discovered that cancer cells package oncogenic messages into tiny particles called extracellular vesicles and send them to neighboring normal epithelial cells. This results in reprogramming of the shape and position of their mitochondria — the cell’s powerhouse — to ultimately alter tissue structure.

These findings, published in the journal Developmental Cell, suggest novel therapeutic targets to disrupt the pro-tumorigenic changes caused by cancer cells to the microenvironment.