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Author: The Wistar Institute

Amelia Escolano, Ph.D.

Written by The Wistar Institute on . Posted in Our Scientists.

Assistant Professor, Vaccine & Immunotherapy Center

The Escolano Lab investigates novel vaccination strategies against highly mutating viruses.

We are interested in understanding the unique features of the humoral and cellular immune responses to sequential immunization, with special focus on the process of antibody affinity maturation in the germinal centers. Our goal is to rationally design vaccination approaches to induce potent and long-lasting antibody responses against pathogens that diversify over time.

Dr. Amelia Escolano is an Assistant Professor in the Vaccine & Immunotherapy Center and a Wistar Institute Assistant Professor in Microbiology at the University of Pennsylvania.

Escolano obtained her BS degree in Biochemistry from the University of Oviedo, Spain and a master’s degree from Centro de Biologia Molecular Severo Ochoa in Madrid, Spain. She received additional training at the University of Turku, Finland and the Genome Research Institute in Cincinnati, Ohio. Escolano obtained her PhD in biochemistry and molecular biology from Autonoma University of Madrid after completing her pre doctoral studies at the Spanish National Center for Cardiovascular Research (CNIC) in Madrid. She trained as a postdoctoral fellow in the laboratory of Michel Nussenzweig at The Rockefeller University in New York and joined The Wistar Institute as an Assistant Professor in 2021. Escolano is a Pew Biomedical Scholar, a recipient of the regional Blavatnik award for young scientists (finalist) and has been recognized with a NIH Director’s New Innovator Award (DP2).

The Escolano Laboratory

215-898-3703

aescolano@wistar.org

The Escolano Laboratory

Viruses such as HIV-1, influenza and SARS-CoV-2 have the ability to rapidly mutate as a mechanism to escape from the host immune system. As a result, highly mutating viruses are largely diverse, with multiple different circulating variants characterized by individual antigenic and infectivity properties. The design of efficacious vaccines against highly diverse viruses is extraordinarily challenging. Despite decades of research, no universal vaccines exist against HIV-1 or influenza. Unfortunately, common vaccination strategies cannot elicit the type of broadly neutralizing antibodies required to confer broad protection against these viruses, and some of the currently available vaccines fail to induce long-lasting protection. Consequently, boost immunizations are advised in order to achieve protection.

The Escolano Lab investigates the use of sequential immunization as a novel vaccination strategy aiming to induce broadly neutralizing antibodies against highly diverse viruses. Using HIV-1 as a model virus, state-of-the-art technologies and animal models including wild type mice, transgenic mice and rhesus macaques, the laboratory studies the humoral and cellular immune responses to sequential immunization. The research goal is to identify guidelines for the design of vaccination approaches to induce long-lasting protection against highly mutating viruses in humans.

Staff

  • Postdoctoral Fellows

    Ignacio Rodriguez Relaño, Ph.D.
    Maria Belen Palacio, Ph.D.
    Marta Tarquis, Ph.D.

  • Graduate Students

    Ashwin Skelly
    Austin Kriews

  • Research Assistant

    Caroline Boroughs
    Sowmya Meka
    Maggie Kerwin

Available Positions

Postdoctoral fellow and research assistant positions are available in the Escolano laboratory. Interested applicants are encouraged to contact aescolano@wistar.org.

Research

  • Sequential Immunization Against HIV-1

    An efficacious antibody-based vaccine against HIV-1 should elicit broadly neutralizing antibodies (bNAbs) targeting conserved epitopes of its envelope (Env) protein. Our previous work showed that common vaccination strategies using repeated boost immunization with the same Env immunogen could not elicit bNAbs. Instead, a new form of vaccination involving sequential immunization was required to elicit highly mutated anti-HIV-1 bNAbs. The reported sequential immunization protocol involved prime immunization with an engineered Env immunogen followed by a series of four additional immunizations with Env immunogens that gradually resembled the native-looking Env. This immunization protocol elicited bNAbs in an immunoglobulin knock-in mouse model with a monoclonal B cell repertoire engineered to carry the inferred germline precursor of a human bNAb (Escolano et al, Cell, 2016). These immunization experiments were the first showing that anti-HIV-1 bNAbs can be elicited by vaccination, and fueled subsequent vaccine design studies. However, despite this significant achievement, no vaccination protocols have been reported that are able to elicit protective levels of bNAbs in wild type organisms with a polyclonal B cell repertoire.

    Wild type organisms mount polyclonal antibody responses when encountering complex antigens such as the HIV-1 Env protein. A predominant component of antibody responses elicited by Env immunogens are antibodies to non-conserved or strain-specific epitopes of Env, with no potential to broadly neutralize HIV-1. These antibodies significantly interfere with the development of bNAbs.

    The Escolano lab investigates the humoral and cellular immune responses to sequential immunization to establish guidelines for vaccine design. We design and evaluate immunogens and sequential immunization strategies to elicit anti HIV-1 broadly neutralizing antibodies in wild type organisms. Our specific goal is to devise approaches to modulate the immunodominance properties of vaccine candidates aiming to focus the antibody responses to the conserved, neutralization-sensitive epitopes of Env.

    Using state-of-the-art technologies for single cell analysis and different animal models including wild type mice, rhesus macaques and a series of recently generated immunoglobulin knock-in and reporter mice, we investigate the process of antibody maturation and the evolution of the different immune compartments upon sequential immunization.

  • Antibody Isolation and Characterization

    Our laboratory has vast experience designing strategies to isolate antigen-specific B cells from wild type mice, humanized mice and non-human primates, and cloning their antibody genes.

    Antibody cloning from single B cells is an essential tool for characterizing humoral immune responses and obtaining valuable therapeutic and analytical reagents. Antibody cloning from individuals with high serologic titers to HIV-1, influenza, malaria, ZIKV, and SARS-CoV-2 has led to new insights that inform vaccine design efforts.

    We have designed cost-effective protocols to identify and purify single antigen-specific B cells, and subsequently clone and produce monoclonal antibodies.

    We are using the newly developed methods to isolate and characterize HIV-1-specific B cells from naïve and immunized mice, from vaccinated or simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and from humans. Remarkably, using our approach, we have isolated one of the first anti-HIV-1 bNAbs from a SHIV-infected rhesus macaque, validating the use of macaques as preclinical models for HIV-1 vaccination studies.

    The Escolano laboratory uses this state-of-the-art methodology to isolate antibodies against bacteria, tumor neoantigens and viruses, including cancer-associated viruses. Characterization of the isolated antibodies is providing very valuable information to guide vaccine design efforts and the development of new preventative and therapeutic approaches.

  • Production Of Knock-in Mice

    The use of animal models in biomedical research has been crucial to investigate the mechanisms of human pathophysiology, evaluate candidate interventions and predict treatment outcomes in humans. Animal Models have been extensively used by the scientific community to examine the cellular and humoral responses to infection and vaccination. Unfortunately, none of these models faithfully recapitulates the setting of a human immune response.

    Humanized mice genetically engineered to recapitulate different aspects of the human humoral and/or cellular immune response are highly desirable. In particular, human immunoglobulin knock-in mice (Ig KI mice) are remarkably valuable for vaccine development and drug discovery, as well as for basic immunology studies related to the analysis of B and T cell responses to infection, vaccination, autoimmunity, or cancer. However, current methods to produce Ig KI mice are inefficient, labor-intensive and require special equipment and expertise to perform zygote microinjections.

    We have developed a novel technology to efficiently and more easily generate monoclonal Ig KI mice using CRISPR/Cas9. The new technology remarkably simplifies the mouse production process, increases knock-in efficiency and reduces breeding time, thus accelerating the production process and reducing cost.

    We are currently using the new technology for high-throughput production of Ig KI mice carrying anti-HIV-1 antibodies, which we use for vaccine design purposes.

    Interestingly, this methodology can be adapted to introduce other genetic modifications in the mouse genome including gene insertions and deletions, thus being of great value to other scientific disciplines. The new technology is especially valuable for engineering events involving insertions of long DNA fragments or genetic modification of more than one locus.

Staff

  • Postdoctoral Fellows

    Ignacio Rodriguez Relaño, Ph.D.
    Maria Belen Palacio, Ph.D.
    Marta Tarquis, Ph.D.

  • Graduate Students

    Ashwin Skelly
    Austin Kriews

  • Research Assistant

    Caroline Boroughs
    Sowmya Meka
    Maggie Kerwin

Available Positions

Postdoctoral fellow and research assistant positions are available in the Escolano laboratory. Interested applicants are encouraged to contact aescolano@wistar.org.

Escolano Lab in the News

  • From Forbes: Meet The 2022 Class Of Pew Scholars In Biomedical Sciences

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

  • Wistar’s Dr. Amelia Escolano Named 2022 Pew Scholar

Selected Publications

  • Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.

    Escolano, A., Steichen, J.M., Dosenovic, P., Kulp, D.W., Golijanin, J., Sok, D., Freund, N.T., Gitlin, A.D. Oliveira, T. Araki, T., et al. “Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.” Cell. 2016 Sep 8;166(6):1445-1458.e12. doi: 10.1016/j.cell.2016.07.030.

  • Immunization Expands B Cells Specific To HIV-1 V3 Glycan In Mice And Macaques.

    Escolano, A., Gristick, H.B., Abernathy, M.E., Merkenschlager, J., Gautam, R., Oliveira, T.Y., Pai, J., West Jr, A.P., Barnes, C.O., Cohen, A.A., et al. “Immunization Expands B Cells Specific To HIV-1 V3 Glycan In Mice And Macaques.” Nature. 2019 Jun;570(7762):468-473. doi: 10.1038/s41586-019-1250-z. Epub 2019 May 29.

  • Sequential immunization of macaques elicits heterologous, neutralizing antibodies targeting the V3-glycan patch of HIV-1 Env.

    Escolano A, Gristick HB, Gautam R, DeLaitsch AT, Abernathy ME, Yang Z, Wang H, Hoffmann MAG, Nishimura Y, Wang Z, Koranda N, Kakutani LM, Gao H, Gnanapragasam PNP, Raina H, Gazumyan A, Cipolla M, Oliveira TY, Ramos V, Irvine DJ, Silva M, West AP Jr, Keeffe JR, Barnes CO, Seaman MS, Nussenzweig MC, Martin MA, Bjorkman PJ. Sequential immunization of macaques elicits heterologous neutralizing antibodies targeting the V3-glycan patch of HIV-1 Env. Sci Transl Med. 2021 Nov 24;13(621):eabk1533. doi: 10.1126/scitranslmed.abk1533. Epub 2021 Nov 24. PMID: 34818054; PMCID: PMC8932345.

  • A Broadly Neutralizing Macaque Monoclonal Antibody Against The HIV-1 V3-Glycan Patch.

    Wang, Z., Barnes, C.O., Gautam, R., Cetrulo Lorenzi, J.C., Mayer, C.T., Oliveira, T.Y., Ramos, V., Cipolla, M., Gordon, K.M., Gristick, H.B., et al. “A Broadly Neutralizing Macaque Monoclonal Antibody Against The HIV-1 V3-Glycan Patch.” Elife. 2020 Oct 21;9:e61991. doi: 10.7554/eLife.61991.

  • Progress Toward Active Or Passive HIV-1 Vaccination.

    Escolano, A., Dosenovic, P., Nussenzweig , M.C. “Progress Toward Active Or Passive HIV-1 Vaccination.” J Exp Med. 2017 Jan;214(1):3-16. doi: 10.1084/jem.20161765. Epub 2016 Dec 21.

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Hildegund C.J. Ertl, M.D.

Written by The Wistar Institute on . Posted in Our Scientists.

Professor, Vaccine & Immunotherapy Center

Ertl’s research centers on developing vaccines for an array of diseases and conditions—including AIDS, chronic viral infections, COVID-19 and some forms of cancer—not typically considered to be treated using this approach. These vaccines aim to protect against future infections and look to create new therapies for diseases already affecting people.

Ertl came to The Wistar Institute as an associate professor in 1987. A native of Germany, she received her medical degree from University of Göttingen. While in medical school, she began her scientific training as a student in the Max Planck Institute of Experimental Medicine. After research fellowships at the Australian National University and the University of Minnesota, Ertl joined the faculty of Harvard University before transitioning to Wistar. She became a full professor at Wistar in 1996 and holds professorships at the University of Pennsylvania School of Medicine and The Children’s Hospital of Philadelphia.

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The Ertl Laboratory

215-898-3863

ertl@wistar.org

The Ertl Laboratory

The Ertl laboratory has pioneered numerous patented technologies to create new vaccines. Much of the laboratory’s efforts focus on developing a new preventative vaccine for rabies—a lethal and underestimated disease that remains a top public health priority across the globe—have yielded useful technologies that the Ertl laboratory is applying to combating other viruses.

The lab is applying its adenovirus vaccine expertise against SARS-CoV-2, utilizing a modified chimpanzee virus as a vaccine delivery vehicle to induce an immune response. They are applying this platform to develop HIV vaccines and creating new therapeutic vaccines against human papillomavirus (HPV), a leading cause of cervical cancer, and chronic hepatitis B virus infection, a major cause of hepatocellular carcinoma.

Staff

  • Senior Staff Scientists

    Zhi Quan Jason Xiang, M.D.
    Xiang Yang Peter Zhou, M.D., Ph.D.

  • Postdoctoral Fellows

    Mohadeseh Hasanpourghadi, Ph.D.
    Mohsen Mohammadi, Ph.D.

  • Wistar Research Assistants

    Wynetta Giles-Davis
    Amara Saha

  • Lab Coordinator

    Christina Cole

Research

Vaccines to SARS-COV-2

We developed vaccines expressing the SARS-CoV-2 spike or nucleocapsid protein. The vaccines are being tested for T and B cell responses in mice. They are being tested in a hamster challenge model.

Therapeutic Cancer Vaccine to Human Papilloma Virus

Vaccines that aim to expand tumor-specific CD8(+) T cells have yielded disappointing results in cancer patients although they showed efficacy in transplantable tumor mouse models. Using a system that more faithfully mimics a progressing cancer and its immunoinhibitory microenvironment, we show that in transgenic mice, which gradually develop adenocarcinomas due to expression of HPV-16 E7 within their thyroid, a highly immunogenic vaccine expressing E7 only induces low E7-specific CD8(+) T-cell responses, which fail to affect the size of the tumors.

In contrast, the same type of vaccine expressing E7 fused to herpes simplex virus (HSV)-1 glycoprotein D (gD), an antagonist of the coinhibitory B- and T-lymphocyte attenuator (BTLA)/CD160-herpes virus entry mediator (HVEM) pathways, stimulates potent E7-specific CD8(+) T-cell responses, which can be augmented by repeated vaccination, resulting in initial regression of even large tumor masses in all mice with sustained regression in more than half of them. These results indicate that active immunization concomitantly with blockade of the immunoinhibitory HVEM-BTLA/CD160 pathways through HSV-1 gD may result in sustained tumor regression.

HIV-1 Vaccine Based on Chimp Serotypes of Adenovirus

This NIH-funded research aimed to test adenoviral recombinants based on simian serotypes for induction of immune responses to gag/pol/rev/env of HIV-1 or SIV-1 in mouse and primate models. Results were promising and part of the vaccines, based on two adenoviral vector vaccines expressing the HIV-1 env protein, are currently being tested in a phase I trial sponsored by HVTN.

Genetic Vaccine to Rabies Virus

The laboratory developed an adenovirus-based vaccine against rabies virus that can provide rapid immunity following a single administration. A simian adenoviral vector termed adenovirus C68 (AdC68) was generated as a molecular clone to express the glycoprotein of rabies virus. In mice, this vector induced complete protection to rabies virus challenge after a single dose. This vaccine also achieves long-term protection in non-human primates after a single dose. A slightly modified version of this vaccine has been tested in collaboration with The University of Oxford. Results were promising and a phase 1b/II trial is being initiated.

Therapeutic HBV Vaccine Based on Chimp Serotypes of Adenovirus

In collaboration with Virion Therapeutics, the laboratory developed a therapeutic vaccine against chronic hepatitis B virus (HBV) infection (CHB). The vaccines target viral polymerase and core proteins. Vaccines are delivered by chimpanzee adenovirus vectors (AdC) of serotype 6 (AdC6) and 7 (AdC7) used in prime-only or prime-boost regimens. The HBV antigens are fused into an early T cell checkpoint inhibitor, i.e., herpes simplex virus (HSV) glycoprotein D (gD), which enhances and broadens vaccine induced CD8+ T cell responses. The vaccines were shown to induce potent CD8+ T cells in mice which can reduce HBV viral loads in a surrogate model of CHB. Clinical trials are planned and expected to commence towards the end of 2022.

Metabolic Manipulation of CD8+ T Cells to Enhance Their Ability to Delay Tumor Progression

Reducing the metabolic stress within a tumor microenvironment could be essential to improve the effectiveness of active cancer immunotherapy. Using a mouse model of melanoma, the laboratory showed that appropriately timed treatment with the PPAR agonist fenofibrate improves the ability of a T cell-inducing cancer vaccine to delay tumor progression. The drug reduces the use of glucose by tumor and tumor stroma cells and promotes the use of fatty acids for their metabolic needs. The increased availability of glucose within the tumor microenvironment in turn allows for its increased use by vaccine-induced tumor-infiltrating CD8+ T cells, which improves their ability to slow tumor progression. The laboratory is currently using a humanized mouse model to test if similar results can be obtained with human melanomas.

Ertl Lab in the News

Selected Publications

  • Immunological Biomarker Discovery in Cure Regimens for Chronic Hepatitis B Virus Infection.

    Gehring, A.J., Mendez, P., Richter, K., Ertl, H., Donaldson, E.F., Mishra, P., Maini, M., Boonstra, A., Lauer, G., Creus, A., et al. “Immunological Biomarker Discovery in Cure Regimens for Chronic Hepatitis B Virus Infection.” J Hepatol. 2022 Mar 5;S0168-8278(22)00127-1. doi: 10.1016/j.jhep.2022.02.020.

  • The Effect of Rapamycin and Ibrutinib on Antibody Responses to Adeno-associated Virus Vector-mediated Gene Transfer.

    Xiang, Z., Kuranda, K., Quinn, W., Chekaoui, A., Ambrose, R., Hasanpourghadi, M., Novikov, M., Newman, D., Cole, C., Zhou, X., et al. “The Effect of Rapamycin and Ibrutinib on Antibody Responses to Adeno-associated Virus Vector-mediated Gene Transfer.” Hum Gene Ther. 2022 Mar 1. doi: 10.1089/hum.2021.258. Online ahead of print.

  • Hepatitis B Virus Polymerase-specific T cell Epitopes Shift in a Mouse Model of Chronic Infection.

    Hasanpourghadi, M., Novikov, M., Newman, D., Xiang, Z., Zhou, X.Y., Magowan, C., Ertl, H.C.J. “Hepatitis B Virus Polymerase-specific T cell Epitopes Shift in a Mouse Model of Chronic Infection.” Virol J. 2021 Dec 7;18(1):242. doi: 10.1186/s12985-021-01712-y.

  • PPARα Agonist Fenofibrate Enhances Cancer Vaccine Efficacy.

    Chekaoui, A., Ertl, H.C.J. “PPARα Agonist Fenofibrate Enhances Cancer Vaccine Efficacy.” Cancer Res. 2021 Sep 1;81(17):4431-4440. doi: 10.1158/0008-5472.CAN-21-0052. Epub 2021 Jul 8.

  • COVID-19 Vaccines Based on Adenovirus Vectors.

    Hasanpourghadi, M., Novikov, M., Ertl, H.C.J. “COVID-19 Vaccines Based on Adenovirus Vectors.” Trends Biochem Sci. 2021 May;46(5):429-430. doi: 10.1016/j.tibs.2021.03.002.

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Daniel Claiborne, Ph.D.

Written by The Wistar Institute on . Posted in Our Scientists.

  • Caspar Wistar Fellow, Vaccine & Immunotherapy Center

  • Immunology, Microenvironment and Metastasis Program, Ellen and Ronald Caplan Cancer Center

  • Scientific Director, Histotechnology Facility

Claiborne is an immunologist focused on understanding how the function of T cells is modulated to create improved immunotherapies, including CAR T cell therapies, against HIV.

Claiborne earned his B.S. in Biochemistry from Florida State University and a Ph.D. in Immunology and Molecular Pathogenesis from Emory University. He completed his postdoctoral training at the Ragon Institute of MGH, MIT, and Harvard and joined The Wistar Institute in 2021 as a Caspar Wistar Fellow.

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The Claiborne Laboratory

215-898-2203

dclaiborne@wistar.org

The Claiborne Laboratory

T cell immunotherapies offer hope for the treatment of malignancies and other chronic diseases. However, natural mechanisms in place to limit immune-mediated pathology ultimately attenuate the T cell response in the setting of chronic antigen exposure, such as is found in chronic viral diseases – including HIV – as well as cancer. A better understanding of the mechanisms underlying T cell exhaustion has the potential to revolutionize T cell immunotherapies, such as chimeric antigen receptor (CAR) T cell therapy, for the treatment of human disease.

The Claiborne lab is rooted in understanding the complex interplay between the virus and the host in HIV transmission, pathogenesis, and persistence. A central focus of the lab is the optimization of CAR T cell therapy for a functional HIV cure. Concordant with efforts to engineer potent CAR T cell therapies against HIV, the Claiborne lab seeks to uncover the mechanisms behind the initiation and maintenance of dysfunctional T cell phenotypes, as the pursuit of these questions is critical to developing the next generation of T cell immunotherapies. To answer these complex questions, the lab leverages the powerful in vivo model system of HIV-infected humanized mice coupled with HIV-directed CAR T cells to study the evolution of antigen-specific T cell function over time.

Staff

  • Research Assistants

    Tyler Yang

  • Graduate Students

    Reyes Acosta (UPenn-CAMB)
    Alexandria Criswell (Drexel)
    Federica Severi (UniBO)

  • Postdoctoral Fellows

    Francesco Pennino, Ph.D.
    Nur Izzah Binti Ismail, Ph.D.

Research

MAPPING THE ONTOGENY OF DYSFUNCTIONAL CAR T CELL PHENOTYPES

Progressive T cell exhaustion and dysfunction due to continuous antigen exposure is a hallmark of chronic viral infections. In situations of uncontrolled HIV replication, we have observed a striking and progressive increase in the co-expression of multiple inhibitory receptors on CAR T cells in humanized mice. Additionally, CAR T cells isolated from viremic humanized mice display attenuated effector function ex vivo when compared to the transferred T cell product at baseline. Using this model system, and through a combination of transcriptomics and ex vivo functional assays, the Claiborne lab intends to map the initiation and maintenance of dysfunctional T cell subsets in an effort to uncover gene pathways/programs that can be targeted to prevent or reverse T cell exhaustion – with the goal of engineering more potent CAR T cell immunotherapies.

MAPPING THE KINETICS, CO-EXPRESSION, AND PLASTICITY OF INHIBITORY RECEPTOR EXPRESSION IN CHRONICALLY STIMULATED CAR T CELLS

We have recently developed a novel in vitro model system for chronic antigen stimulation of CAR T cells with the ability to specifically titrate antigen dosing as well as remove antigen stimulation at any time. Using this unique model system, we have mapped the longitudinal and concomitant expression of multiple inhibitory receptors on human CD4 and CD8 CAR T cells. We further aim to understand the functional consequences of multiple inhibitory receptor expression, whether periods of rest due to antigen removal can reverse certain inhibitory receptor profiles, and which profiles are indicative of long-term transcriptional reprogramming.

INFLUENCE OF VIRAL CHARACTERISTICS ON HIV-SPECIFIC T CELL FUNCTION

Previous work by the lab has demonstrated that the intrinsic viral replicative capacity (vRC) of the transmitted/founder virus can greatly impact the disease course of HIV-infected individuals. Individuals infected with high-vRC variants display exacerbated immunopathology characterized by T cell activation and exhaustion, concomitant with rapid CD4+ T cell loss. This may also represent an unrecognized hurdle for a functional HIV cure, as individuals with high-vRC viruses may be more refractory to CAR T cell therapy or other interventions. The lab endeavors to use a previously generated suite of chimeric viruses exhibiting distinct vRC phenotypes to define the extent to which vRC affects CAR T efficacy in vitro and in vivo and to elucidate the mechanisms responsible.

ROLE OF THE INNATE IMMUNE SYSTEM IN MODULATING CAR T CELL FUNCTION

Recent evidence in a humanized mouse model of acute lymphoblastic leukemia demonstrates that interactions between CAR T cells and the innate immune system can enhance CAR T cell function but can also contribute to cytokine release syndrome (Norelli M et al., Nature Medicine, 2018). During HIV infection, vigorous innate immune responses ultimately contribute to chronic immune activation and inflammation, which is associated with accelerated pathogenesis. These data suggest a complex role for components of the innate immune system, with the potential for enhancing or attenuating functions, in modulating CAR T cell efficacy in the context of HIV infection. We have created a series of reagents to specifically ablate or enhance monocyte function in humanized mice and endeavor to use this in vivo system to elucidate the role of the innate immune system in affecting HIV-specific CAR T cell function.

Claiborne Lab in the News

Selected Publications

  • Dual CD4-based CAR T Cells With Distinct Costimulatory Domains Mitigate HIV Pathogenesis In Vivo.

    Maldini, C.R., Claiborne, D.T., Okawa, K., Chen, T., Dopkin, D.L., Shan, X., Power, K.A, Trifonova, R.T., Krupp, K., Phelps, M., et al. “Dual CD4-based CAR T Cells With Distinct Costimulatory Domains Mitigate HIV Pathogenesis In Vivo.” Nat Med. 2020 Nov;26(11):1776-1787. doi: 10.1038/s41591-020-1039-5. Epub 2020 Aug 31.

  • Innate Immune Reconstitution in Humanized Bone Marrow-Liver-Thymus (HuBLT) Mice Governs Adaptive Cellular Immune Function and Responses to HIV-1 Infection.

    Garcia-Beltran, W.F., Claiborne, D.T., Maldini, C.R., Phelps, M., Vrbanac, V., Karpel, M.E., Krupp, K.L., Power, K.A., Boutwell, C.L., Balazs, A.B., et al. “Innate Immune Reconstitution in Humanized Bone Marrow-Liver-Thymus (HuBLT) Mice Governs Adaptive Cellular Immune Function and Responses to HIV-1 Infection.” Front Immunol. 2021 May 26;12:667393. doi: 10.3389/fimmu.2021.667393. eCollection 2021.

  • Immunization of BLT Humanized Mice Redirects T Cell Responses to Gag and Reduces Acute HIV-1 Viremia.

    Claiborne, D.T. , Dudek, T.E., Maldini, C.R., Power, K.A., Ghebremichael, M., Seung, E., Mellors, E.F., Vrbanac, V.D., Krupp, K., Bisesi, A., et al. “Immunization of BLT Humanized Mice Redirects T Cell Responses to Gag and Reduces Acute HIV-1 Viremia.” J Virol. 2019 Sep 30;93(20):e00814-19. doi: 10.1128/JVI.00814-19. Print 2019 Oct 15.

  • Replicative Fitness of Transmitted HIV-1 Drives Acute Immune Activation, Proviral Load in Memory CD4+ T Cells, and Disease Progression.

    Claiborne, D.T., Prince, J.L., Scully, E., Macharia, G., Micci, L., Lawson, B., Kopycinski, J., Deymier, M.J., Vanderford, T.H., Nganou-Makamdop, K., et al. ”Replicative Fitness of Transmitted HIV-1 Drives Acute Immune Activation, Proviral Load in Memory CD4+ T Cells, and Disease Progression.” Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):E1480-9. doi: 10.1073/pnas.1421607112. Epub 2015 Feb 17.

  • Role Of Transmitted Gag CTL Polymorphisms In Defining Replicative Capacity And Early HIV-1 Pathogenesis.

    Prince, J.L., Claiborne, D.T., Carlson, J.M., Schaefer, M., Yu, T., Lahki, S., Prentice, H.A., Yue, L., Vishwanathan, S.A., Kilembe, W., et al. “Role Of Transmitted Gag CTL Polymorphisms In Defining Replicative Capacity And Early HIV-1 Pathogenesis.” PLoS Pathog. 2012;8(11):e1003041. doi: 10.1371/journal.ppat.1003041.

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Wistar’s Medicinal Chemist Dr. Joe Salvino and the Journey to Drug Discovery

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

Joseph Salvino, Ph.D., medicinal chemist and professor in the Molecular & Cellular Oncogenesis Program and scientific director of the Molecular Screening & Protein Expression facility at The Wistar Institute, spent more than 20 years in the pharmaceutical industry’s drug discovery before coming to Wistar. Dr. Salvino collaborates with many Wistar scientists on programs to help identify novel small molecule lead compounds that could evolve into future drugs.

Here at the intersection of biology and chemistry is where Dr. Salvino and his team work best. Their medicinal and synthetic chemistry skills complement our investigators’ biology expertise. It’s a process wherein Dr. Salvino helps to optimize a hit compound our Wistar scientists identified or tries to identify a new lead compound for an interesting new target.

When Wistar scientists want to identify a compound that can produce a certain desired effect, Dr. Salvino works to optimize that compound’s ability to achieve its target effect. These early-stage compounds that show promise are called “hits,” and Dr. Salvino investigates these hits in a variety of biochemical settings.

Dr. Salvino’s expertise is in optimizing early-stage hits by improving target binding affinity and functional activity. His aim is to increase a compound’s biological potency and improve drug-like properties. To achieve this goal Dr. Salvino works closely with biologists to understand the molecular target. He focuses on how a small molecule will engage the target to elicit a biological response.

This crucial foundational research is the bedrock of the drug discovery process. It’s here that assays are developed with the throughput to support iterative medicinal chemistry optimization efforts that can quickly evaluate twenty or so compounds in a few days. The goal of lead optimization is to identify a suitable compound that could become a therapy to treat cancer and other disease. This is the compelling fundamental work that Wistar basic researchers accomplish before a drug discovery company considers translating what Wistar scientists have identified and potentially converts a Wistar discovery into a drug useful in health care.

As Wistar’s medicinal chemist, describe how you fit into Wistar’s scientific efforts?

I work in collaboration with Wistar scientists and scientists at neighboring universities to help identify a series of compounds suitable as a pharmacological means to modulate their target of interest. My job is to identify a suitable compound, part of a “hit-to-lead” series usually identified from a screening campaign, to test pharmacologically the effects of small molecule treatment both in vitro and in vivo.

In a lay friendly way tell us your process working with the scientists.

We work with other scientists by identifying and improving on small molecules that engage their protein target of interest. These small molecules may inhibit, stimulate, or degrade their protein and be biologically active in a cell expressing their protein, or where their protein is the cause for the disease we are trying to treat. My team needs to learn as much as we can about the molecular target from our collaborator.

We work with many Wistar investigators—typically those who are looking to identify or improve on a small molecule as a potential therapeutic agent for a disease related to their target. Often the investigator has already identified a small molecule to test their hypothesis. My team works in collaboration to improve or develop a new molecule, focusing on improving selectivity, potency, or its in vivo drug-like properties.

The Wistar Institute Molecular Screening & Protein Expression Core is under my direction. This group can develop assays that typically can be run in a plate-based format to provide a high-throughput approach to support our medicinal chemistry efforts. For example, when medicinal chemists are trying to identify an optimized compound, we need to synthesize and evaluate 10-50 different analogs that are related but have slight differences in their structure. We do this to probe for “structure activity relationships”—the changes required to improve binding affinity to a protein target or to improve its functional activity. Both binding affinity and functional efficacy are very important to optimize a molecule, even though its functional efficacy is what a biologist wants to study.

Interestingly, a typical drug discovery effort from a pharmaceutical company requires the synthesis of about 2000-3000 compounds per target to identify a development candidate.

How do you start working with scientists?

We start to work together because of a common interest in a target or a disease, such as treatment of melanoma, ovarian, or breast cancer or EBV associated cancer, or others. We normally start collaborating because of our common interests and complementary skills.

What aspects of your work do you like most?

I enjoy the interface between chemistry and biology. I love finding new compounds with interesting biological activity in collaboration with my colleagues, especially for interesting new targets. I like working with the screening core to help develop new methods to test compounds. We spend a lot of time synthesizing chemical probes, such as a binding probe, which greatly facilitate assay development. A binding probe, or also sometimes called a tracer, is used in a competitive binding assay, where an unlabeled compound will compete for binding with the tracer. For this type of study, we can determine the binding affinity of an unlabeled test compound.

Wistar does not make drugs or therapies but advances discoveries that can move into drug discovery as future therapeutics.

Wistar Researchers Discover Potential Target for Gastric Cancers Associated with Epstein-Barr Virus

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

PHILADELPHIA—(August 22, 2023)—Now, scientists at The Wistar Institute have discovered a potential target for gastric cancers associated with Epstein-Barr Virus; study results were published in the journal mBio. In the paper, Wistar’s Tempera lab investigates the epigenetic characteristics of gastric cancer associated with the Epstein-Barr Virus: EBVaGC. In evaluating EBVaGC’s epigenetics — the series of biological signals associated with the genome that determines whether a given gene is expressed — the Tempera lab highlights a target that could advance as a future treatment for this type of cancer.

The work of Italo Tempera, Ph.D., associate professor in the Gene Expression & Regulation Program in the Ellen and Ronald Caplan Cancer Center, at The Wistar Institute, and collaborators demonstrates that an epigenetically active compound called decitabine disrupts the genome of EBVaGC by epigenetically modifying the cancer’s DNA, a finding that offers the potential for a new approach to treating EBVaGC.

“What we have identified is essentially a self-destruct button within this kind of cancer, and our paper shows that we figured out how to press that self-destruct button,” said Tempera. “Normally, a latent virus that reactivates and starts to kill cells is a bad thing. But by switching that viral lytic process back on in these cancer cells by using epigenetic signaling, we’re effectively getting the virus to kill the cancer cells that it’s responsible for in the first place.”

The research — supported by a research program project grant, otherwise known as a P01-series grant, from The National Institute of Health (NIH) — includes scientists from The Wistar Institute, The Coriell Institute for Medical Research and Brigham and Women’s Hospital of Harvard Medical School.

In EBVaGC, the cancer cells’ DNA is hypermethylated: the DNA contains a high percentage of cytosine with a 5-methyl group attached to it (relative to normal, unmethylated cytosine). As a silencer of gene expression, DNA methylation allows EBV to remain latent. This methylation pattern plays a significant role in regulating the EBV latency-lysis cycle within the cancer cells. DNA methylation, as an epigenetic factor, usually functions as a gene-silencing mechanism, particularly in certain regions of the genome; a methylated gene still exists within the genome — methylation does not delete the genetic information — but methylation can prevent the protein the gene encodes from being transcribed.

To disrupt this epigenetic profile, the researchers turned to decitabine, a compound known for its ability to reduce DNA methylation levels (i.e., to hypomethylate the DNA). Tempera and his co-authors treated two cell lines that were derived from EBVaGC tumors with decitabine. The cell lines that received the treatment demonstrated massive reductions in DNA methylation across the genome relative to the control as assessed by a variety of epigenetic assay techniques.

In observing the effects of decitabine treatment on EBVaGC, Tempera’s team found a significant disruption of the cancer’s epigenetic profile. The EBV genome within EBVaGC treated with decitabine resulted in widespread, mostly uniform hypomethylation of the EBVaGC epigenome (with a few regional exceptions). Tempera and his co-authors discovered that the hypomethylating effect of decitabine treatment reactivated the lytic cycle of the latent EBV in the cancer cells. Because lysis is lethal to cells, the epigenetic reactivation of lysis within gastric cancer associated with EBV offers a promising potential treatment for the specific subset of EBVaGC.

“Now we know that we can use the epigenome of Epstein Barr Virus against the gastric cancer that it affects — that’s an exciting potential cancer therapy we have as a result of investigating the interplay between epigenetic patterns and disease lifecycle,” explained Tempera.

Co-authors: Sarah Preston-Alp, Lisa Beatrice Caruso, Chenhe Su, Samantha S. Soldan, Davide Maestri, Andrew Kossenkov, Giorgia Napoletani, Paul M. Lieberman and Italo Tempera of The Wistar Institute; Kelsey Keith and Jozef Madzo of The Coriell Institute for Medical Research; and Benjamin Gewurz of Brigham and Women’s Hospital of Harvard Medical School.

Work supported by: National Institutes of Health (NIH) grants P30 CA010815, R01 AI130209, R01 GM124449, P01 CA269043, R01 DE017336, R01 CA259171, R01 CA09360, R01 AI1535086, R01 AI164709, R01 CA228700, U01 CA275301, R50 CA211199 and T32 CA09171.

Publication information: “Decitabine disrupts EBV genomic epiallele DNA methylation patterns around CTCF binding sites to increase chromatin accessibility and lytic transcription in gastric cancer” from mBio.

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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.

Award-Winning Biotech Training Program to Begin Second Recruitment to Connect Philadelphians with Quality Jobs in the Region’s Rapidly Growing Life Sciences Sector

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

PHILADELPHIA (August 14, 2023) – Partners in Greater Philadelphia’s life sciences ecosystem are expanding their commitment to connecting a wider range of Philadelphians, including residents from disadvantaged communities, with career opportunities in the burgeoning biotech industry with the announcement of an upcoming recruitment for an award-winning biotech training program.

The launch of recruitment for the second cohort of The “Biomedical Technician Training Program: Aseptic Manufacturing” follows on the heels of the successful implementation of a pilot program that resulted in the training and hiring of 10 program graduates in March 2023. Recruitment for the program will begin August 22 and go through September 6. Recruitment and application information can be found on The Navy Yard website (navyyard.org/skills).

In a field that often requires PhDs or master’s degrees for most roles, the program – “Biomedical Technician Training Program: Aseptic Manufacturing” – creates opportunities for Philadelphians with at least a high school equivalency. The initiative is one way the region is working together to meet the talent needs in its rapidly growing cell and gene therapy sector.

“If you really want a change, really want something different, and you’re ready to make a difference in your life this would be a great opportunity, and it doesn’t require a degree,” said Iyana Pearson, a graduate of the first training cohort. “You have to go into it from an open mind and open heart and know it is probably completely different from anything that you have ever done in life.”

The “Biomedical Technician Training Program: Aseptic Manufacturing,” the first of its kind in the region, is an innovative, high-touch workforce training model that was collaboratively designed with Iovance Biotherapeutics. The program connects Philadelphians to robust biomedical training at The Wistar Institute and offers program graduates a direct path to full-time, career-ladder employment as Associate Aseptic Manufacturing Technicians at Iovance.

The second cohort of this program is made possible through the strong support of Congresswoman Mary Gay Scanlon (PA-05), in which PIDC received a $525,000 grant for its Navy Yard Skills Initiative (NYSI) and a $100,000 commitment from Ensemble/Mosaic’s Navy Yard Building Better Foundation. Ensemble/Mosaic is the exclusive developer of a 109-acre mixed-use development at the Navy Yard. The grant and the donation will enable the continuation of the program, which will be open this year to 20 new participants.

The first cohort launched in the summer of 2022 generated more than 400 applicants. In total, 13 students graduated from the program, and 10 were offered full-time employment at Iovance Biotherapeutics in positions starting at $25/hr. The program received the 2022 BioBuzz Workforce Champion Award, which was given to the program for a measurable contribution to enhancing the biotech workforce within the BioHealth Capital Region and Philadelphia.

“We had tremendous success with participants who completed our first cohort of this program and want to expand the pool of well-trained biomedical laboratory technicians here in Philadelphia,” said Dr. Kristy Shuda McGuire, Wistar Dean of Biomedical Studies. “This happened through cross-sector partnership with a group committed to the mission of creating a diverse life science talent pipeline. Only then could we offer effective training to adult learners that connects them to employment opportunities. This is the key to building the workforce that will support our region as a hub for life science innovation today and into the future.”

Recruitment begins August 22 for the 24-week paid program, which will include class- and lab-based training provided by The Wistar Institute and professional development from University City District’s West Philadelphia Skills Initiative, culminating in a 12-week externship at Iovance Biotherapeutics, Inc., a biotechnology company focused on innovating, developing and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, whose cell therapy manufacturing center is located at the Philadelphia Navy Yard. Program participants will gain the skills needed to be considered for employment as associate aseptic manufacturing technicians – jobs starting at $25/hour – at the conclusion of the program in March 2024. Associate aseptic manufacturing technicians are responsible for maintaining a sterile lab environment, assembling sterile products, stocking supplies, and documenting processes of biomedical manufacturers in supporting the creation of cell therapies.

For the West Philadelphia Skills Initiative (WPSI), the opportunity to work with Iovance on a second project allowed for delivery of the next level of service with a program that has the benefit of experience. “There is now just not proof of concept but proof of product. We are poised as a region to be best in class for building diverse and deep talent pools which can continue to push Philadelphia to become an even more competitive location for the life science industry. Through our collaborations with Wistar and Iovance and in our sector partnership building work under the Good Jobs Challenge federal investment, we see a full range of possibilities and abundant opportunities,” said Cait Garozzo, Executive Director at the West Philadelphia Skills Initiative.

“Following our success and valuable experience with the inaugural cohort of the Biomedical Technician Training Program, Iovance is looking forward to hosting the second cohort in collaboration with Wistar, the West Philadelphia Skills Initiative, the Chamber of Commerce, and PIDC. We hope this training program will continue to grow and serve as a model to build deep, diverse life sciences talent pipelines across Greater Philadelphia and beyond,” said Jamie Crawford, Vice President, Commercial Manufacturing, Iovance Biotherapeutics, Inc.

Much of the growth of the region’s cell and gene therapy hub is taking place at the Navy Yard, where Iovance Cell Therapy Center is located, and in University City, where The Wistar Institute is located, and where the West Philadelphia Skills Initiative has built its reputation as one of the leading workforce intermediaries in the country. Among other factors, the sector’s growth is reflected in the more than 60 cell and gene therapy companies that now call Greater Philadelphia home; the $3 billion in investment the region’s cell and gene therapy sector attracted in 2021; the 80 percent increase in employment at cell and gene therapy companies, contract research organizations, and contract development & manufacturing organizations in the past three years; and the more than 10.8 million square feet of existing space and 2.7 million square feet under construction to support the sector’s growth.

PIDC‘s Navy Yard Skills Initiative (NYSI), a workforce development training program created to address the talent needs of the employers located at the Navy Yard, has been crucial in engaging its life sciences employers to create non-traditional pathways into cell and gene therapy careers, including Iovance. Currently, the Navy Yard has nearly one million square feet of life sciences lab, production, and office space and 4 million square feet planned.

“We are excited to continue this innovative partnership with The Wistar Institute, West Philadelphia Skills Initiative, Iovance, and the Chamber of Commerce and expand on this award-winning program that connects Philadelphians with life-changing, quality career opportunities in one of the region’s fastest growing sectors,” said Kate McNamara, PIDC’s Senior Vice President, Navy Yard. “With the success of the first cohort, there is now a proven training model that creates equitable access and lowers the barrier of entry to prepare Philadelphians to work in advanced life sciences. Since we began the Navy Yard Skills Initiative in 2020, we have connected nearly 100 Philadelphians with quality jobs at great Navy Yard companies like Philly Shipyard, Tastykake, Jefferson Health, and Iovance. We’re committed to continue creating exciting and accessible opportunities at the Navy Yard for all Philadelphians.”

A workforce talent study for the region’s cell and gene therapy sector, conducted by Econsult Solutions for the Chamber of Commerce for Greater Philadelphia and the University City Science Center, identified job opportunities for talent at all levels, including those not requiring a four-year degree, particularly as companies grow and begin building manufacturing capacity. The workforce talent study is part of the Chamber’s broader efforts to proactively address the talent needs of the cell and gene therapy community through research, strategic promotion, early-career talent-focused events, and convening employers.

“When two of Greater Philadelphia’s strongest training organizations collaborated with industry partners to launch the pilot of this workforce development program, we envisioned something that could be replicated and repeated many times over to support our region’s rapidly expanding center for life sciences and cell and gene therapy,” said Sarah Steltz, Vice President of Economic Competitiveness, Chamber of Commerce for Greater Philadelphia. “Iovance’s commitment to a second cohort of the Biomedical Technician Training Program, and the launch of another cohort with Children’s Hospital of Philadelphia, demonstrate the possibilities for partnership. The Chamber is grateful to Iovance and CHOP for their commitment to skills-based hiring and a model that we know other employers will also embrace.”

“This is exactly the type of program that Ensemble/Mosaic’s Navy Yard Building Better Foundation seeks to support. One of our missions is the investment in the professional development of minorities and women in the Navy Yard by providing access to education, job training, capital and mentorship, and we look forward to the members of this second cohort finding success,” said Leslie Smallwood-Lewis, COO & Co-Founder of Mosaic Development Partners JV.

Calibrated specifically to meet the needs of a burgeoning sector, the Biomedical Technician Training Program is designed for replication across industry employers. The West Philadelphia Skills Initiative and The Wistar Institute partnered with Children’s Hospital of Philadelphia on a cohort that will be connected to research positions there.
“The CHOP Research Institute is excited to partner with WPSI and The Wistar Institute to offer an accelerated, hands-on life sciences and training curriculum customized with input from CHOP researchers, providing once-in-a-lifetime training and job placement opportunities for residents of West Philadelphia to pursue careers in biomedical laboratory sciences,” said Senior Vice President for Research Administration and Operations Michelle Lewis, MS, CRA, CCP. “Our first cohort is learning in-demand skills that will unlock talent resources in the City of Philadelphia to advance pediatric care and make a difference for CHOP’s patients and families.”

Program Information
The 24-week paid training program begins with 10 weeks of evening classes at The Wistar Institute focused on preparing participants with a foundation in cellular and molecular biology as applicable to the life sciences industry. After the first 10 weeks, participants will take part in a full-time, hands-on laboratory orientation at The Wistar Institute before transitioning to externships at the Iovance iCTC (Cell Therapy Center) at the Navy Yard.

Throughout the 24-week program, the West Philadelphia Skills Initiative will support participants by offering professional development courses and coaching.
Select candidates who complete the program may interview for a full-time position at Iovance, with a starting pay of $25/hour.

Recruitment for the program, which The Navy Yard will launch on August 22 with online applications on its website (navyyard.org/skills), continues through September 6. The program will officially welcome selected participants at The Wistar Institute on September 22, and continue through early March 2024.

To apply, candidates need to be Philadelphia residents 18 years of age or older, with a high school diploma or GED, and test at a 12th grade level in reading, literacy, and math. Twenty participants will be selected for the program.

About the West Philadelphia Skills Initiative
The West Philadelphia Skills Initiative (WPSI) is one of the nation’s most successful workforce development organizations. For 10 years, WPSI has solidified its role as one of the highest performing workforce intermediaries in the country by building customized talent solutions that bridge the divide between unemployed Philadelphians seeking opportunity and employers seeking talent. WPSI focuses on professional development and career coaching for adults. www.philadelphiaskills.org

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 recently announced the creation of the Hubert J. P. Schoemaker Education and Training Center to bring together its education programs for high school, undergraduate and graduate students as well as postdoctoral fellows, with its expanding pre-apprenticeship and apprenticeship training, including the newly named Fox Biomedical Research Technician (BRT) Apprenticeship. staging.wistar.org

About Iovance Biotherapeutics
Iovance Biotherapeutics aims to be the global leader in innovating, developing and delivering tumor infiltrating lymphocyte (TIL) therapies for patients with cancer. We are pioneering a transformational approach to cure cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells in each patient. Our lead late-stage TIL product candidate, lifileucel for metastatic melanoma, has the potential to become the first approved one-time cell therapy for a solid tumor cancer. The Iovance TIL platform has demonstrated promising clinical data across multiple solid tumors. We are committed to continuous innovation in cell therapy, including gene-edited cell therapy, that may extend and improve life for patients with cancer. For more information, please visit www.iovance.com.

About PIDC and the Philadelphia Navy Yard
PIDC is Philadelphia’s public-private economic development corporation. Since acquiring the 1,200-acre site from the federal government in 2000, PIDC has been the master developer and site operator of the Navy Yard. PIDC’s mission—to spur investment, support business growth, and facilitate developments that create jobs, revitalize neighborhoods, and drive growth to every corner of Philadelphia—strongly informs its strategy for the Navy Yard, where the focus is on building a cohesive community that fosters employment, innovation, and production. PIDC manages all aspects of the property’s management and development, including master planning, leasing, property management, infrastructure development, utility operation, and structuring development transactions. www.PIDCphila.com | www.navyyard.org

About The Chamber of Commerce for Greater Philadelphia’s CEO Council for Growth
The Chamber of Commerce for Greater Philadelphia’s CEO Council for Growth (CEO Council) leads our region forward by envisioning a stronger, more competitive community, convening decision makers, taking action, and advocating for policies and practices that strengthen our regional economy. The CEO Council advocates through its members and engaged stakeholders to enhance economic growth and prosperity in the region. We prioritize the revitalization and enhancement of our region’s talent, mobility, and innovation. The CEO Council’s Cell & Gene Therapy Initiative is leveraging Greater Philadelphia’s specialized assets to accelerate growth and promote the region as the global hub of research, talent, capital, and companies in cell & gene therapy, gene editing, and connected health. For more information, visit www.ceocouncilforgrowth.com

About Ensemble/Mosaic
Ensemble/Mosaic is a joint venture between Ensemble Investments, LLC and Mosaic Development Partners. The partnership is the exclusive developer of a 109-acre mixed-use development at the Navy Yard in Philadelphia, including office, life science, retail, hospitality and the first residential complex to be built in the community. Ensemble/Mosaic, in partnership with PIDC, directed the creation of the 2022 Navy Yard Comprehensive Plan. Deeply committed to Environmental, Social & Governance (ESG), Ensemble/Mosaic has pledged $1B over the next 20 years to diversity, equity and inclusion (DEI) hiring and initiatives. ensemblemosaic.com

Media Contacts

Dr. Alex Price

The Wistar Institute Recruits Virology Expert Alexander Price, Ph.D., to Cancer Center

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

PHILADELPHIA—(August 9, 2023)— The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, is pleased to announce the appointment of Alexander Price, Ph.D., as assistant professor in the Gene Expression and Regulation Program of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute.

Price’s research focuses on how viral genomes are controlled during infection — specifically, how viruses regulate and exploit RNA transcription and processing. His work aims to identify and exploit therapeutic targets underlying how viruses hijack cellular transcriptional machinery to combat disease.

“We are immensely pleased to welcome Alex Price to Wistar. The Institute is committed to expanding our understanding of viruses’ role in cancer as well as other disease, and the establishment of the Price Lab at Wistar represents a significant investment in the Institute’s research capacity,” said Dario Altieri, M.D., Wistar president and CEO, director of the Ellen and Ronald Caplan Cancer Center and the Robert and Penny Fox Distinguished Professor. “Alex’s experience in viral RNA and DNA research makes it clear that he will make compelling, fresh contributions to Wistar’s research program.”

Price earned his B.S. degree in Genetics and Cell Biology at Washington State University. In 2016, he received a Ph.D. in Molecular Genetics and Microbiology from Duke University. Price completed his postdoctoral research in affiliation with the University of Pennsylvania and the Children’s Hospital of Philadelphia.

“I’m thrilled to have the opportunity to launch the Price Lab at Wistar,” said Price. “Between Wistar’s reputation for scientific excellence and the Institute’s state-of-the-science research facilities, I have every confidence in establishing a productive, collaborative laboratory here.”

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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

Joy Taylor

The Wistar Institute Appoints Life Sciences Consultant and Entrepreneur Joy Taylor to its Board of Trustees

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

Philadelphia – (August 8, 2023) – The Wistar Institute, a global leader in biomedical research in cancer, immunology and infectious disease, is pleased to welcome Joy Taylor to its Board of Trustees. Taylor is CEO of EastEdge Consulting Services, a Pennsylvania-based management consulting firm focused on organizational and operational improvement.

An accomplished C-suite executive and entrepreneur, Taylor brings to the role more than 25 years of cross-functional experience in operations, change management, and executive leadership, specifically in the life sciences sector. Taylor will serve on the Board’s Communications and Marketing Committee.

“I’m honored and privileged to be invited to participate in such an ambitious and purpose-driven organization like The Wistar Institute,” said Taylor. “I’ve focused my career helping large, complex life sciences organizations build action-oriented strategies that improve operational efficiencies and maximize their potential. I’m incredibly excited to help further elevate and showcase Wistar’s innovative and impactful research to an even broader audience.”

Prior to EastEdge Consulting, Taylor served as the National Managing Principal of Organizational and Operational Transformation at Grant Thornton LLP, a leading audit, tax, and advisory firm. She was the founder of TayganPoint Consulting Group, a management consulting firm focused predominantly on large-scale business transformation in the life sciences, and for 13 years acted as CEO before its acquisition by Grant Thornton in 2018. She has also worked as a consultant for IBM, a quality leader at GE, and has founded multiple businesses.

“Joy brings a deep understanding of the life sciences industry, and an impressive track record of management consulting.” 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. “Her vision and insight will be critical as we continue to pursue building a life science ecosystem centered on excellence, collaboration, education and innovation.”

Taylor received a BA in Communications Studies from the University of Florida and her MBA, with a concentration in Marketing and Statistics, from the University of South Florida.

In addition to her service with Wistar, Taylor currently serves as a board member of WeMake Autism, is the vice chair of the board of Foster Nation, and is an active foster parent, having fostered 26 children over the last seven years. She lives in Yardley with her husband and four children.

Dr. Paul Lieberman talks with two scientists in the lab

Wistar-Led Team Awarded More Than $12 Million Grant from the NCI to Investigate Link Between Epstein-Barr Virus and Carcinomas

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

PHILADELPHIA — (JULY 26, 2023) — It’s been known since the 1960s that Epstein-Barr Virus (EBV) causes a variety of cancers, but research has overwhelmingly focused on its connection to lymphomas. Now, a multidisciplinary team of scientists led by The Wistar Institute has been awarded a more than $12 million National Cancer Institute (NCI) Program Project Grant (P01), a highly competitive five-year grant that includes a cross section of researchers from various disciplines and institutions throughout the country. The multidisciplinary team led by Wistar scientists is exploring the role of Epstein-Barr Virus in epithelial cancers. Epithelial cells form functional structures in organ tissue throughout the human body; they are often the site for solid organ cancers, including the most common cancers, which are known as carcinomas.

The new research will focus on basic questions about how EBV infection of normal epithelial cells transforms them into cancer-cells. Scientists also intend to build on this research to identify better and more selective therapeutic targets.

“We are investigating unexplored aspects of EBV and malignancies, potentially uncovering unique characteristics or pathways that can be targeted for therapeutic intervention,” said Italo Tempera, Ph.D., associate professor of the Gene Expression & Regulation Program of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute. “This fresh perspective could lead to groundbreaking discoveries and innovative treatment strategies for EBV and epithelial malignancies.”

The project brings together scientists from The Wistar Institute and Harvard University, including experts in epigenetics, metabolomics and drug discovery. It’s the first time researchers from this variety of disciplines have combined their efforts to focus entirely on the EBV-epithelial cancer link.

“We’ve put together a new strategy, a new way of attacking the problem,” said Paul Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor and director of the Center for Chemical Biology and Translational Medicine at Wistar. “By working together across different modalities, there’s an opportunity for each of us to learn from the synergy and expertise of the other investigators.”

EBV is one of the most common human viruses, infecting an estimated 95% of people by the time they reach adulthood. Symptoms are usually mild, and most people recover within a few weeks. However, the virus can remain latent in the human body for years or even decades, and it causes some people to develop cancer later in life.

While research has historically focused on lymphomas, EBV-linked epithelial cancers are both more common and more deadly. Epithelial cancers represent 75% of the 200,000 EBV-related cancer cases diagnosed each year, and these cancers also have higher mortality rates and treatment failures.

“This grant put together a team that is now focused on this type of cancer that has been neglected, even though it’s the most common form of EBV cancers,” Lieberman said. The grant will fund three main research projects. The first will look at how EBV establishes a long-term infection within epithelial cells. The second will study how it causes genetic and metabolic changes to trigger cancer growth. Finally, researchers will use these findings to investigate new therapeutic strategies.

The research builds on past work by Lieberman’s lab, which has focused on developing small molecule inhibitors targeting EBV. He said the new project would focus on studying drugs that are already in development, and looking for ways to make them more targeted or use them in combination with other therapies.

Tempera said the group’s integrated approach sets it apart.“Our project will study both metabolic and epigenetic vulnerabilities simultaneously,” he said. “Combining these two aspects can provide a comprehensive understanding of the role of EBV infection in cancer and its underlying mechanisms, leading to unique insights and therapeutic opportunities.”

Co-authors: Ben Gewurz of Harvard; Joseph Salvino, Samantha Soldan, Andrew Kossenkov, Louise Showe, and Qin Liu of Wistar.

Wistar Scientists Collaborate with University of Buea Researchers to Identify Plant-Based Medicinal Compounds

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

Advanced computer models from Cameroon allow scientists to screen hundreds of compounds efficiently.

Wistar Research Assistant Professor Dr. Ian Tietjen of the Montaner Lab — in his collaboration with Dr. Fidele Ntie-Kang, Associate Professor and Head of the University of Buea Center for Drug Discovery (www.ub-cedd.org) in Cameroon — works to expedite and improve the drug discovery process, particularly for plant-based compounds that could be potentially used to treat HIV. With funding from the Bill & Melinda Gates Foundation through a Calestous Juma Science Leadership Fellowship awarded to Dr. Ntie-Kang, they use an advanced computer modeling system to screen hundreds upon hundreds of candidate compounds for experimental and clinical efficacy. The model draws on the Pan-African Natural Product Library, an index of thousands of compounds from African plants, many of which are known to have medicinal properties. The program is designed to ensure that the models are continuously updated and improved with new information, which allows researchers to screen for potentially therapeutic drugs both quickly and accurately.

“Let’s say you have an idea of how to treat HIV by targeting a specific molecule,” explained Dr. Ntie-Kang, an international expert in computational chemistry. “And let’s say 500 compounds could potentially target this molecule. Rather than test all 500 of those compounds, and spend money and time on all those tests, we can use a model to computer-screen those 500 compounds and narrow them down by drug-potential criteria to the best eight candidates. It’s much more efficient and cost-effective.”

Dr. Tietjen agreed. “Fidele’s work is immensely helpful for generating testable hypotheses. I’ve been able to work with him to identify starting points for future potential therapeutic compounds and leads for investigating viral ion channels, for example. Before I started collaborating with him, the process was much slower.”

The collaboration has been fruitful for both scientists, with Dr. Tietjen working to test potential therapeutic compounds at Wistar while Dr. Ntie-Kang hopes to share and exchange the laboratory techniques and research infrastructure knowledge with his own drug discovery research team, based at the new University of Buea Centre for Drug Discovery (UB-CeDD) in Cameroon. In a testament to the power of virtual inter-institutional partnerships at Wistar, both scientists are quick to note that their collaboration, which dates back to 2015, has been successful in advancing both their respective research programs — despite the fact that they had not met in person until 2022.