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Author: The Wistar Institute

Dario C. Altieri, M.D.

  • President and Chief Executive Officer

  • Director, Ellen and Ronald Caplan Cancer Center

  • Robert and Penny Fox Distinguished Professor, Genome Regulation and Cell Signaling Program

Altieri is interested in how mechanisms of cellular adaptation or “plasticity” are universally exploited in cancer for disease maintenance and progression. Multiple cellular pathways of response to stress, metabolic rewiring, and control of cell death are invariably subverted in human tumors, and often confer more aggressive disease traits including the ability to disseminate to distant organs, or metastasis. A detailed, molecular, cellular, and genetic understanding of tumor plasticity could uncover new therapeutic targets and identify novel approaches to interfere with metastatic competence, which remains the primary cause of death for cancer patients.

Born in Milan, Italy, and educated at the University of Milan School of Medicine, Altieri is a physician-scientist trained in internal medicine and holds a postgraduate degree in clinical and experimental hematology. In 1987, he joined the Scripps Clinic and Research Foundation in La Jolla, California, first as a research fellow and later as a member of the faculty.

In 1994, Altieri became an associate professor at the Boyer Center for Molecular Medicine at Yale University School of Medicine, where he was named professor with tenure in 1999 and member of the Yale Cancer Center executive committee. In 2002, Altieri was recruited as the founding chair of the Department of Cancer Biology at the University of Massachusetts Medical School and Director of the UMass Memorial Cancer Center. Altieri joined the Institute as the Wistar Cancer Center Director and its first Chief Scientific Officer in September 2010. He was appointed as President and Chief Executive Officer of Wistar in 2015 while continuing to serve as Director of the recently renamed National Cancer Institute (NCI)-designated Ellen and Ronald Caplan Cancer Center.

The Altieri Laboratory

215-898-3774

mcolelli@wistar.org

The Altieri Laboratory

The Altieri laboratory currently studies the role of mitochondria in cancer. The lab pursues the overarching hypothesis that multiple mitochondrial functions in bioenergetics, buffering of reactive oxidative species (ROS), inter-organelle communication with the endoplasmic reticulum (ER), and retrograde gene expression are invariably reprogrammed in malignancy and exploited to enable extraordinary plasticity and tumor heterogeneity for disease progression. Mechanistically, Altieri and his team have implicated these pathways in supporting tumor cell proliferation, evasion from multiple forms of cell death and, importantly, heightened tumor cell motility and invasion, leading to metastatic disease. To understand the role of tumor plasticity and mitochondrial reprogramming in disease progression and dissemination, Altieri uses a multidisciplinary collection of biochemical, cellular, and molecular approaches in vitro, xenograft, and genetic animal models of localized and metastatic disease, in vivo, and analysis of clinically-annotated primary patient samples. Although mechanistic in nature, Altieri lab research goals have clear translational and disease-relevant implications. Altieri’s work has demonstrated that therapeutic targeting of mitochondrial reprogramming in cancer is feasible, and may uniquely disable multiple mechanisms of disease progression, including metastatic competence across a broad spectrum of genetically heterogeneous tumors. Accordingly, a first-in-class, mitochondria-targeted small molecule inhibitor of the molecular chaperone Heat Shock Protein-90 (Hsp90) was developed and characterized by the Altieri laboratory (Gamitrinib) and has recently entered first-in-human clinical trial in patients with advanced cancer (ClinicalTrials.gov NCT04827810).

Staff
  • Research Assistant Professors

    Jagadish Ghosh, Ph.D.
    Michela Perego, Ph.D.

  • Postdoctoral Fellows

    Andrew Milcarek, Ph.D.
    Minjeong Yeon, Ph.D.

Research

Multifunctional Survivin Signaling in Cancer

The Altieri laboratory is credited with the discovery and characterization of the survivin gene. Approaching 9,500 citations currently in PubMed, survivin is recognized as a fundamental cancer gene, a pleiotropic molecular hub for multiple pathways of cell survival, mitosis, adaptation to stress and metabolic reprogramming, as well as a validated therapeutic target in the clinic. Altieri’s contributions in this field have run the gamut from the discovery of survivin to the characterization of its unique role at the interface between cell death and mitosis in cancer, to clinical validation as a therapeutic target and predictive/prognostic disease biomarker.

Mitochondrial Proteostasis in Tumor Adaptation

Over the past decade, the Altieri lab’s work uncovered a novel role of protein folding quality control in mitochondria as a key driver of tumor progression. These studies elucidated mechanisms of protein homeostasis, or proteostasis maintained by Heat Shock Protein-90 (Hsp90) chaperones as well as AAA+ proteases in mitochondria, characterized their role in adaptive regulation of apoptosis, metabolic reprogramming and retrograde gene expression, and identified novel mechanisms of tumor adaptation to microenvironment stress stimuli, including hypoxia or exposure to molecular therapy.

Mitochondria and Metastasis

How tumors that switch to an inefficient glycolytic metabolism, i.e. the Warburg effect, manage to accomplish highly energy-demanding tasks of cell motility and invasion has long remained elusive. Altieri’s work demonstrated that mitochondrial oxidative phosphorylation is required to fuel membrane dynamics of cell motility, resulting in increased tumor chemotaxis, invasion and metastasis. Mechanistically, Altieri showed that this pathway involves the redistribution of energetically active mitochondria to the peripheral cytoskeleton of tumor cells, where they provide a concentrated, spatiotemporal energy source to power membrane lamellipodia dynamics, turnover of focal adhesion complexes, and sustained phosphorylation of cell motility kinases.

Mitochondrial Control of Tumor Plasticity

Recent findings from the Altieri group have demonstrated that mitochondrial reprogramming is a universal cancer trait that imparts unique plasticity to a full spectrum of tumor responses, from early-stage malignant transformation to full blown tumor growth, to regulation of go-or-grow decisions, the dynamic and reversible switch between cell proliferation and cell migration states. The Altieri lab showed that mitochondrial control of tumor plasticity involves panoply of signaling pathways, including generation of ROS, exosome-dependent intercellular communication, and stabilization of HIF1 resulting in a transcriptionally-active, pseudo-hypoxic state.

Novel Cancer Drug Discovery Approaches

The Altieri laboratory has pioneered the concept of targeting mitochondrial reprogramming for novel cancer therapeutics. The group uses a combination of mitochondrial-targeted peptidomimetic antagonists and small molecule ATPase inhibitors to disrupt mitochondrial Hsp90-directed protein folding, inhibit oxidative bioenergetics and abolish MFF cytoprotection at the mitochondrial outer membrane. In preclinical studies, these first-in-class mitochondrial-targeted agents (Shepherdin, Gamitrinib, MFF 8-11) were well-tolerated, demonstrated a unique “mitochondriotoxic” mechanism of action, and delivered potent, cytotoxic anticancer activity alone or in combination with molecular therapies in localized and disseminated tumor models, in vivo.

Altieri Lab in the News

  • Abs 2019-nCoV RNA virus - 3d rendered image on black background.

    Wistar Institute Researchers Identify Parkinson-related Protein’s Role in Cancer and T Cell Activation

    Press Releases

    PHILADELPHIA — (September 17th, 2024) — The Wistar Institute’s President and CEO, Dario C. Altieri, M.D., and team have demonstrated the role of Pa…

  • Wistar Institute President & CEO Dr. Dario Altieri Appointed to the Board of Directors of the Chamber of Commerce for Greater Philadelphia

    Press Releases

    PHILADELPHIA — (October 22, 2024) —President and CEO of The Wistar Institute Dario Altieri, M.D., has been appointed to the Board of Directors of t…

  • Celebrating the Pancreatic Cancer Alliance

    Video

    Dr. Dario Altieri, President and CEO of The Wistar Institute, shares the story of the Pancreatic Cancer Alliance’s founding and the vital mission it serves on its 20th anniversary in February 2024.

Selected Publications

  • Parkin activates innate immunity and promotes antitumor immune responses

    Perego, M., Yeon, M., Agarwal, E., Milcarek, A. T., Bertolini, I., Camisaschi, C., Ghosh, J. C., Tang, H. Y., Grandvaux, N., Ruscetti, M., Kossenkov, A. V., Preston-Alp, S., Tempera, I., Auslander, N., & Altieri, D. C. (2024). Parkin activates innate immunity and promotes antitumor immune responses. The Journal of clinical investigation, 134(22), e180983. https://doi.org/10.1172/JCI180983

  • Parkin ubiquitination of Kindlin-2 enables mitochondria-associated metastasis suppression

    Yeon, M., Bertolini, I., Agarwal, E., Ghosh, J. C., Tang, H. Y., Speicher, D. W., Keeney, F., Sossey-Alaoui, K., Pluskota, E., Bialkowska, K., Plow, E. F., Languino, L. R., Skordalakes, E., Caino, M. C., & Altieri, D. C. (2023). Parkin ubiquitination of Kindlin-2 enables mitochondria-associated metastasis suppression. The Journal of biological chemistry, 299(6), 104774. https://doi.org/10.1016/j.jbc.2023.104774

  • Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability

    Ghosh, J. C., Perego, M., Agarwal, E., Bertolini, I., Wang, Y., Goldman, A. R., Tang, H. Y., Kossenkov, A. V., Landis, C. J., Languino, L. R., Plow, E. F., Morotti, A., Ottobrini, L., Locatelli, M., Speicher, D. W., Caino, M. C., Cassel, J., Salvino, J. M., Robert, M. E., Vaira, V., … Altieri, D. C. (2022). Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability. Proceedings of the National Academy of Sciences of the United States of America, 119(8), e2115624119. https://doi.org/10.1073/pnas.2115624119

  • A cancer ubiquitome landscape identifies metabolic reprogramming as target of Parkin tumor suppression

    Agarwal, E., Goldman, A. R., Tang, H. Y., Kossenkov, A. V., Ghosh, J. C., Languino, L. R., Vaira, V., Speicher, D. W., & Altieri, D. C. (2021). A cancer ubiquitome landscape identifies metabolic reprogramming as target of Parkin tumor suppression. Science advances, 7(35), eabg7287. https://doi.org/10.1126/sciadv.abg7287

  • Small Extracellular Vesicle Regulation of Mitochondrial Dynamics Reprograms a Hypoxic Tumor Microenvironment.

    Bertolini, I., Ghosh, J. C., Kossenkov, A. V., Mulugu, S., Krishn, S. R., Vaira, V., Qin, J., Plow, E. F., Languino, L. R., & Altieri, D. C. (2020). Small Extracellular Vesicle Regulation of Mitochondrial Dynamics Reprograms a Hypoxic Tumor Microenvironment. Developmental cell, 55(2), 163–177.e6. https://doi.org/10.1016/j.devcel.2020.07.014

  • Syntaphilin controls a mitochondrial rheostat for proliferation-motility decisions in cancer.

    Caino, M. C., Seo, J. H., Wang, Y., Rivadeneira, D. B., Gabrilovich, D. I., Kim, E. T., Weeraratna, A. T., Languino, L. R., & Altieri, D. C. (2017). Syntaphilin controls a mitochondrial rheostat for proliferation-motility decisions in cancer. The Journal of clinical investigation, 127(10), 3755–3769. https://doi.org/10.1172/JCI93172

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Wistar Scientists Honored, Speak at AIDS Education Month Event

Pride Month in Philadelphia, PA, is celebrated alongside another worthy cause: AIDS Education Month, an event series organized by the nonprofit Philadelphia FIGHT to raise awareness of those living with AIDS, AIDS treatments & healthcare and AIDS research. The Wistar Institute has collaborated with Philadelphia FIGHT for decades to advance their mission to cure HIV/AIDS.

At the opening celebration for AIDS Education Month on Thursday, June 1st, Philly FIGHT honored two Wistar senior scientists for their decades of contribution to HIV/AIDS research. Drs. Livio Azzoni and Emmanouil Papasavvas — each a senior scientist in the HIV program and Wistar Montaner Lab — received the Kiyoshi Kuromiya award, which honors a community Philadelphia activist, Kiyoshi Kuromiya that galvanized national and global awareness to the needs of persons living with HIV. Kuromiya organized with the Gay Liberation Front for gay rights and founded the Philly chapter of ACT UP to advocate for those impacted by the AIDS epidemic, and the award bearing his name recognizes those who have similarly impacted our community and made a difference to the lives of persons living with HIV.

Dr. Papasavvas was moved by the honor, and he took the opportunity to thank everyone involved in the collaborative work of the research process: “Research is not working alone; we all work together, trying to find the path to discover cures for all diseases, and right now, for HIV.”

Upon accepting his award, Dr. Azzoni also emphasized the teamwork necessary for science by speaking to the importance of both institutional support and patient focus in the search for an AIDS cure: “By doing patient-oriented research, we aim at involving all stakeholders in all stages, from design to implementation.” Both men received standing ovations from the crowd.

Dr. Montaner then joined the stage to participate in a panel discussion titled “The Evolution of HIV Research,” where he was accompanied by moderator and Director of the Philadelphia Department of Public Health’s Division of HIV Health, Dr. Kathleen A. Brady; Chief Scientific Officer and Medical Director of the Jonathan Lax Treatment Center, Dr. Karam Mounzer; Philadelphia FIGHT Director of Research, Emily Hiserodt, MPH; and longtime AIDS advocate, survivor and Chair of the BEAT-HIV Community Advisory Board, William Carter.

The panel sought to answer a compelling question: in the context of medical advances, why is research that seeks an HIV cure still important?

Panelists’ answers addressed several areas. William Carter, as an AIDS survivor, pointed out that an absolute cure would eliminate his need to take medication on an indefinite basis or receive regular bloodwork. Dr. Mounzer spoke to the fact that functional remission, while a tremendous achievement, still comes with reduced life expectancy and general stressors — like comorbidities and side-effects from the maintenance medications — relative to the HIV-negative population.

Dr. Montaner agreed with his fellow panelists on these points and expressed his belief in the macroscopic utility of reaching an HIV cure:

“First, investments made in understanding how HIV persists in somebody over a lifetime have benefited Society as a whole. We have one clear example: COVID. The clinical trials network and trained staff that supported COVID vaccine trials was made possible by the infrastructure that was already in place supporting studies on developing an HIV vaccine or novel therapies.

Second, reaching an HIV cure will hopefully remove the stigma directed towards persons living with HIV.”

Finally, scientific advances in one area of human health, Dr. Montaner emphasized, do not simply remain there: they carry over to different areas of study and move those fields forward, too. “If we can crack chronic infection in those living with HIV — or even just get closer towards that cure — we’re going to get insights into how to advance research into added diseases at the same time.”

Wistar’s Biomedical Technical Training Program Featured on Fox 29 Good Day Philadelphia

The Wistar Institute’s Biomedical Technical Training (BTT) Program was recently featured on Fox 29’s Good Day Philadelphia. Dr. Kristy Shuda McGuire, Dean of Biomedical Studies, and 2022 Program graduate Tylier Driscoll, discussed the history of the training program and Tylier’s experience as a participant. For more than 20 years, the BTT pre-apprenticeship has helped to prepare community college students for positions in biomedical science labs. The Program has recently expanded to reach even more students in the region. Following his completion of the BTT Program, Tylier was hired by BioAnalysis, LLC, a Philadelphia-based contract research organization (CRO).

View the full interview.

The Wistar Institute Appoints Former City Solicitor Sozi Tulante to Its Board of Trustees

PHILADELPHIA — (May 26, 2023) — The Wistar Institute, a global leader in biomedical research in cancer, immunology and infectious disease, is pleased to welcome Sozi Tulante to its Board of Trustees. He is currently General Counsel of Form Energy, a Massachusetts-based energy storage technology and manufacturing company.

A respected legal scholar and strategist, Tulante comes to the role with an extensive background in corporate and intellectual property law, policy matters, regulatory issues, and a record of building and leading diverse and sophisticated teams.

“I’m incredibly honored to join the Wistar board and help further its inspiring mission,” said Tulante. “I see it as a crown jewel of Philadelphia. Almost everyone knows someone who has been afflicted with cancer, but few know about the innovative research needed to develop the promising treatments to fight this deadly disease. That all starts here with Wistar research, and that’s something that people can really understand and support.”

Prior to leading Form Energy’s legal, compliance, and ethics functions, Tulante was a litigation partner at the global law firm Dechert LLP, and a professor and fellow at the University of Pennsylvania Carey Law School. From 2016 to 2018, he served as Philadelphia City Solicitor, where he was in charge of all of the City’s legal affairs, advised the Mayor and other City leaders on high-profile and sensitive issues, and managed the 215 lawyers of the Law Department. He is also a former Assistant U.S. Attorney and previously served as a partner at another law firm.

“Sozi’s extensive legal expertise and understanding of intellectual property, along with his familiarity managing complex, high-performing organizations, will be an incredible asset in helping Wistar achieve its mission of producing groundbreaking advances in world health,” said Dario C. Altieri, M.D., Wistar president and CEO, Director of the Ellen and Ronald Caplan Cancer Center, and Robert and Penny Fox Distinguished Professor. “His ability to distill the complexities of an organization and support Wistar’s strategic vision make him an ideal partner.”

Tulante earned his J.D., cum laude, from Harvard Law School, and his B.A., cum laude, from Harvard College. He is originally from the Democratic Republic of Congo before coming to the United States as a refugee and now lives minutes away from Wistar’s headquarters in West Philadelphia with his family.

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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 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 scientists’ early-stage discoveries shorten the path from bench to bedside. wistar.org\

Photo Credit: Diego Radzinsch / © 2023 ALM Global Properties, LLC

Wistar Scientists Successfully Engineer a Goldilocks Construct: Therapeutic Antibody Could Be a Future Medicine to Improve Outcomes for Melanoma

In recent years, multimodal therapies have emerged as a route to treat cancer by delivering different types of treatments together to improve effectiveness. However, the more modalities there are, the more complex the production and effects of these lifesaving treatments can become.

Wistar researchers have engineered a linked molecule that enables a three-modality therapy for treating melanoma. They accomplished this by connecting a cytokine and an antibody—which would ordinarily be administered separately—and then engineering a form that was pro-inflammatory enough to fight the cancer cells but not so inflammatory as to cause complications or reduce survival outcomes, according to a recently published study in Frontiers in Immunology.

“We took aspects of a cancer treatment regimen and tried to simplify that by combining antibody and cytokine together,” said Nicholas Tursi, the lead author on the study and a graduate student researcher in the lab of Dr. David Weiner, executive vice president, director of the Vaccine & Immunotherapy Center, and W.W. Smith Charitable Trust Distinguished Professor at The Wistar Institute. “I focused on engineering an intermediate cytokine that is efficacious but also has an acceptable pro-inflammatory profile—a Goldilocks approach.”

The engineered “Goldilocks” cytokine Tursi and his colleagues, including Dr. Weiner and Dr. Daniel Kulp, Associate professor in Wistar’s Vaccine & Immunotherapy Center, engineered to test their antibody cytokine chimera was called HL2-KOA1, a modified designer version of the T cell growth factor IL-2. This engineered molecule used in a combination therapeutic regimen was effective at promoting survival in a rigorous melanoma model.

“What this suggests is that we could use other antibodies or cytokines to engineer the immune response to further extend efficacy,” said Tursi. He is hopeful that this research will serve as the foundation for developing other antibody cytokine chimeras that work for melanoma and potentially other cancers.

Balancing Act: It’s a Fine Line Between Inflammation and Immunity When Viruses are Involved

Dr. Mohamed Abdel-Mohsen’s Pioneering Research on Siglecs Spotlights Their Role Helping the Immune System Recognize Viral Infections, and as Promising Future Therapy

Dr. Mohamed Abdel-Mohsen and his virology lab at The Wistar Institute review their work with a new class of immune checkpoints called Siglecs to discover the delicate balance between inflammation and immunity. Their findings could drive novel approaches for reducing damaging inflammation due to viral infections during HIV and possibly SARS-CoV-2, as well.

Twenty-five years ago, it was believed that the sequencing of the full human genome would solve all problems and cure all diseases. Today, scientists are discovering that human biology is much more complicated. To better understand cancer and antiviral activity, the field of glycobiology and the human-specific checkpoints known as Siglecs hold the key for richer, more diverse information and the promise of tailored medicines. 

Every immune cell in the human body has many sugar-binding proteins, and some, called negative checkpoint inhibitors, can suppress the immune function of cells. While immunity is important for health, when the immune system reacts too aggressively, it can harm the body — both by triggering excessive inflammation, and by blocking other critical immune functions, both which can make diseases more severe.

In a recently published, in-depth review in the Lancet journal EBioMedicine, Wistar virologist and glycobiologist Mohamed Abdel-Mohsen, Ph.D., looks at how inhibiting and activating immunological switches by manipulating these negative checkpoint inhibitors may both control inflammation and boost immunity during viral infections. 

The quest to learn more about finding the delicate balance between inflammation and immunity in viruses stems from the Abdel-Mohsen lab’s earlier work with both HIV and SARS-CoV-2. Some of the lab’s previous research looked at the relationship between molecules called glycans and siglecs, and how they help diseases evade the immune system. Glycans are a type of sugar molecule that coats cells in the body. In diseased cells, these glycans change to match special receptors, called siglecs, found on the surface of disease-fighting immune cells such as “natural killer” cells. By binding their glycans to these siglec receptors, researchers showed, the infected cells are able to blind the immune cells and avoid detection.

Previous research by Abdel-Mohsen’s lab has shown how interactions between siglecs and glycans play an important role in regulating the immune system when the body is fighting cancer. In their new paper, the researchers looked at the role this process plays in viruses. 

Viruses use several techniques to help them evade immune surveillance, including employing these negative checkpoint inhibitors to change the glycans, or sugars, on the surface of infected cells. Based on their previous discoveries, Abdel-Mohsen’s lab is now working on new treatments that will manipulate these interactions, supercharging the immune system’s ability to target and destroy infected cells.

They recently discovered a new approach that selectively targets and disables these interactions on the surface of HIV-infected cells, effectively making HIV “killable” for the first time. They’re also studying how these glyco-immune checkpoint interactions may help SARS-CoV-2, the virus that causes COVID-19, evade natural killer immune surveillance — and how those interactions could be targeted.

Siglecs are proteins that bind to glycans (sugars) and regulate the signals of immune cells, as well as the body’s inflammatory responses. By learning how to flip the switch to turn ‘on’ the checkpoints that boost immunity, and turn ‘off’ those that reduce inflammation, Wistar scientists hope to better understand and find new approaches for treating cancer, HIV, and potentially even “long COVID.”

The lab is now exploring siglecs to study the tug-of-war that occurs between viruses and the immune systems, with a goal of better understanding how immunological equilibrium is regulated during viral infections. The challenge, Abdel-Mohsen says, is to find ways of precisely managing this immunological equilibrium in a way that enhances the immune response without triggering excessive inflammation or inhibiting other critical immune functions. 

“If we really want to learn the most about human life, we must look at the glycan,” Abdel-Mohsen says. “Understanding glycobiology will help us as a scientific community to better understand the differences between humans and other organisms—as well as the differences that exists between humans. Investments in this next-level, bold science will allow us to achieve advances in precision medicine by developing specific medicines for specific diseases.” 

Coordination/Synthetic Chemist Returns to Cameroon Ready to Train Next Generation of African Scientists on Wistar’s World-Class Analytic Chemistry Techniques

“Our hope is to build a center with the same reflection of Wistar in science and administration.”

In three short months as a Visiting Scholar with The Wistar Institute in Philadelphia, Donatus Bekindaka Eni, BSc., MSc., Ph.D., a lecturer from the University of Buea in the South West Region of Cameroon, experienced a number of career and life-changing firsts. Despite having earned progressive degrees in Biochemistry, Chemistry and then Inorganic Chemistry, it was in a Wistar lab where he first experienced the liquid chromatography-mass spectrometry (LC-MS) and Nuclear Magnetic Resonance (NMR) analytic chemistry instruments. He also witnessed at Wistar the enzyme-linked immunosorbent assays (ELISA) protocol in action. Finally, and perhaps most-eye opening, for the first time in his life, this scientist from tropical Central Africa opened his curtains to a landscape dusted in snow.

A lecturer and published author, Dr. Bekindaka Eni is the third academic from the University of Buea to travel to Wistar as part of a multi-year collaboration between the two research institutions. Wistar is collaborating with the University in the development of Center for Drug Discovery (UB-CeDD) through the Calestous Juma Science Leadership Fellowship awarded to Fidele Ntie-Kang (grant award number: INV-036848 to University of Buea) where scientists study medicinal plants, natural product compounds, and locally synthesized chemical compounds to treat infectious diseases impacting the Sub-Saharan continent, especially on SARS_CoV-2 and HIV.

Dr. Ntie-Kang, who heads the University research center, briefly visited Philadelphia last fall, while University Ph.D. student Chantal Emade Nkwelle spent last September to February for immersive training in many of Wistar’s laboratory techniques. Last fall, Wistar’s Dr. Ian Tietjen, Research Assistant Professor in the Montaner Lab, traveled to Cameroon to help create a strategy that would best apply Wistar’s resources to the University’s needs to expand antiviral and drug discovery abilities.

Now, upon his return to Cameroon, Dr. Bekindaka Eni will train University of Buea scientists and students on the analytical techniques he learned first-hand during his time learning alongside Wistar colleagues.

“We finally have the facilities in Cameroon, and now our hope is to build a center with the same reflection of Wistar in science and administration,” Dr. Bekindaka Eni says. “It may take several years to catch up. After all, Wistar is quite an old institution! The University of Buea shall gain so much from this visit.”

Scientific valorization of traditional knowledge

UB-CeDD will be among the first on the African continent to use computer-aided methods to learn more about herbal compounds passed down through generations by traditional healers. By determining the chemical pharmacophores responsible for the antiviral or antibacterial activity of medicinal plants, scientists can identify the particular isolate in each that is responsible for their healing qualities, predict chemical toxicity, and discover how they function to treat illnesses, such as HIV or SARS-CoV-2, that disproportionately afflict African nations.

“These spiritual doctors have told us what a plant can cure. Now, our research will help us better understand what the different products in that plant consist of, and how they function to cure a particular illness; that is, valorization of traditional knowledge,” Dr. Bekindaka Eni says.

“Scientific valorization of traditional knowledge will be key to helping our people live in good health.”

Superb science

While at Wistar, Dr. Bekindaka Eni spent every possible moment in Wistar’s synthetic labs, especially appreciating the opportunity to monitor reactions using LC-MAs. This analytical chemistry technique combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry. In Cameroon, scientists currently use less powerful thin-layer chromatography (TLC) plates to monitor the progress of a reaction or ascertain the effectiveness of purification.

“LC-MS is are one of the things that really captured me,” he said. “I was taught in my B.Sc. and we applied it in both M.Sc. and Ph.D. program on the principle of LC-MS and how it works, but I’d never seen it. At Wistar, I not only got to see it, I used it. It was quite exciting!”

Other highlights of his time with Wistar were the idea exchanges from weekly lab meetings run by Luis J. Montaner, D.V.M., D.Phil., and Joseph Salvino, Ph.D., and time spent in Wistar’s Molecular Screening & Protein Expression Facility managed by Joel Cassel. It was there that Dr. Bekindaka Eni became skilled at using the ELISA protocol, an important diagnostic tool in plant and medicine pathology. The protocol detects the presence of antigens in biological samples and is commonly used to test for antibodies indicating HIV or SARS-CoV-2 infection – a skill he is now eager to pass on to students at the University of Buea.

“The science level at Wistar is superb,” he notes.

Dr. Bekindaka Eni acknowledges that the underlying medicinal synthetic approach for organic synthesis is the same for scientists at both ends of the Wistar/University of Buea exchange, with one great advantage in the States being the use of high-tech equipment.

“In Wistar labs, scientists purify compounds by the use of Biotage®. In Cameroon, we do it manually,” he says. “Other than equipment, however, I was very happy to understand that what we do down there is not too different from what is done at Wistar.”

Regardless of method, the goal in organically synthesizing these products is also the same in either nation, which makes this intercontinental collaboration especially meaningful.

“At Wistar or in Cameroon, we’re all doing this work to save lives.”

Notes From the Field: Seeing Research in Action

More than 1,000 supporters gathered in Fairmont Park for PanCAN PurpleStride Philadelphia 2023 to support the Pancreatic Cancer Action Network (PanCAN). Wistar’s Dr. Rahul Shinde is a PanCAN research grant recipient, and our lab was honored to attend the event and represent the scientific community. People of all ages wore purple to show support with many teams commemorating loved ones lost. I, too, walked in memory of a good friend and uncle who both lost their battles with pancreatic cancer. 

The atmosphere was emotional and inspiring as we heard from a 19-year survivor who described his journey through treatment and recovery. The 5-year survival rate has increased from 10% to 12% in the last few years due in part to PanCAN research and funding. It is their goal to reach a 20% survival rate by 2030.

PanCAN PurpleStride Philadelphia raised over $600,000 with 60 similar events held nationwide. The funds support services for patients and their families, along with research grants to improve early detection and treatment of pancreatic cancer. The Shinde Lab raised more than $1,000 thanks to the support of family and friends. 

Walking among this Philadelphia community of supporters reminds us all of our responsibility to make our research count. PanCAN PurpleStride Philadelphia was a realization of how meaningful our work is. There is heartbreak surrounding pancreatic cancer, but also considerable hope in scientific advancement. 

Notes From the Field Series is written by a member of Wistar’s scientific community and reflects on life, both in and out of a busy biomedical research lab. SK Reiser is a graduate student in the lab of Dr. Rahul Shinde.

After 10 Years as Chief Financial Officer, Joe Trainor Readies for Retirement

It is often said that the measure of a person is in more than just their accomplishments. For Dario Altieri, CEO of The Wistar Institute, trying to sum up the tenure of Joe Trainor, who will be retiring this month as Wistar’s Chief Financial Officer, is not as easy as just rattling off his many achievements.

Under Trainor’s leadership, in the past 7 years, Wistar has doubled its grant funding and tripled its endowment. The effort hasn’t gone unnoticed. In 2022 Joe was recognized by the Philadelphia Business Journal as CFO of the Year for his management of the Wistar finances. He was also recently honored by the University City District, a local organization devoted to addressing economic and quality of life issues in the University City section of Philadelphia, where he served as treasurer for more than 25 years.

With the list of accomplishments out of the way, Altieri followed up with more about who Trainor is: a man of humility and compassion, who supports his team and sees his colleagues as one large family. And true to form, when Trainor took the podium to speak, he was quick to attribute his own success to that of his team. “Without them, I would not accomplish any of this, so thank you.”

As a parting gift, the lifelong Phillies fan received a Philadelphia Phillies T-shirt and a framed photo of the Wistar Institute building signed by his colleagues – a fitting tribute for who he is and what he’s done.

Now, Wistar is on the hunt for a new CFO and has engaged executive search firm Odgers Berndston to identify potential candidates for the role. Interested candidates can contact Kian Ringwood for details or to submit a resume.

GeneOne and Wistar Institute Collaborate to Develop Small Molecule Therapeutics to Protect Humans from Nipah Virus

PHILADELPHIA — (May 10, 2023) — GeneOne Life Science, Inc.(“GeneOne” KOSPI: 011000), a leading biopharmaceutical company specializing in developing nucleic-acid based treatments and novel small-molecule therapeutics, and The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease, and vaccine development, headquartered in Philadelphia, Pennsylvania, announce a collaboration to identify novel small molecules capable of inhibiting Nipah virus entry into cells and to develop these into preclinical leads for future advancement into global Phase I clinical trials for the treatment and/or post-exposure prophylaxis of Nipah virus infection.

This program anchored at The Wistar Institute is under the direction of Dr. Luis J. Montaner, Kean Family Professor, director of Wistar’s HIV-1 Immunopathogenesis Laboratory and leader of the HIV Research Program, Vaccine & Immunotherapy Center. Montaner’s team has extensive experience in developing small molecule therapies against infectious diseases including HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Drug screening and small molecule design will be conducted by Dr. Joseph Salvino, professor in Wistar’s Molecular & Cellular Oncogenesis Program, scientific director of Wistar’s Molecular Screening & Protein Expression Facility, and an industry trained medicinal chemist.

Nipah virus is a zoonotic RNA virus of the genus Henipavirus, that first appeared on farms in Malaysia and Singapore in humans and pigs. Animals or humans exposed to bodily fluids from infected bats, the animal reservoir of Nipah virus, are susceptible to infection. Since 1999, Nipah outbreaks have occurred in other countries of Southeast Asia. Outbreaks of Nipah disease have occurred most frequently in Bangladesh and India since 1999 and have been associated with severe neurological disease as well as high mortality (40-70% death rate). Due to its epidemic potential and insufficient countermeasures against it, the World Health Organization (WHO) has identified Nipah virus as a high priority pathogen for research and development.

“It is an important step for global health that GeneOne and The Wistar Institute are joining forces to develop novel therapies against Nipah virus as a recognized high priority pathogen with future pandemic potential,” said Dr. Montaner.

While there are no approved vaccines or drugs to combat Nipah virus, GeneOne’s Chief Scientific Officer, Dr. Kar Muthumani and colleagues recently demonstrated that a synthetic nucleic acid vaccine they developed could result in an effective anti-Nipah virus cellular and humoral immune response in mice.

Dr. Muthumani said, “We are excited about the immunogenicity of our Nipah vaccine, and now we are pleased to collaborate with The Wistar Institute to develop new small molecule inhibitors to add to our portfolio of countermeasures against Nipah infection. GeneOne has always been an innovator and leader in designing synthetic nucleic acid vaccines against emerging infectious diseases (EIDs) and we expect collaborations such as this to help us add new therapeutics to our portfolio that can be used alone or paired with our vaccines to create stronger countermeasures against EIDs.”

Young K. Park, Chief Executive Officer of GeneOne commented that “In addition to vaccines, there is a critical need for drugs and other therapies that block virus transmission from animals-to-humans and even humans-to-humans. While the goal of this project is to develop drugs that block Nipah virus infection, the methods and tools employed and developed here carry great future potential in creating new drugs against other emerging zoonotic diseases that threaten global health. Moreover, since Nipah virus is a deadly pathogen for which there is currently no vaccine or treatment, GeneOne is eager to contribute our R&D expertise to this collaboration for the health of global citizens.”

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About GeneOne Life Science Inc.
GeneOne Life Science Inc., headquartered in Seoul, South Korea is an international biotechnology company driven by creativity and innovation and focused on developing nucleic acid encoded vaccines against infectious diseases to address global needs. Its small molecule portfolio of immunomodulators address diseases such as prevention of upper respiratory bacterial and viral diseases, and treatment of autoimmune and inflammatory diseases.

VGXI, Inc., GeneOne’s wholly-owned subsidiary located in Texas, is the global leading contract developer and manufacturer (CDMO) for cGMP DNA plasmid manufacture. The company is the leading contract manufacturer of DNA plasmids for use in vaccines, gene therapies, and cell therapies. VGXI has recently expanded into the manufacture and development of mRNA.

For more information, visit http://www.genels.com and http://www.vgxii.com.

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 scientists’ early-stage discoveries shorten the path from bench to bedside. wistar.org

Media Contacts:
GeneOne
Jackie Kwon
+82-2-3458-4032
jakwon@genels.com

The Wistar Institute
Darien Sutton
+1 215-898-3988
dsutton@wistar.org