Author: The Wistar Institute

Weiner directs a translational molecular immunology research team focused on creating novel immunotherapy approaches for disease prevention and treatment using synthetic nucleic acid technology. Accomplishments of the team and collaborators include the first clinical studies of DNA vaccines, with a focus on advances in gene optimization and electroporation (EP)-mediated DNA delivery. Their work has revitalized the field, rapidly and safely moving new advances into human studies. These include the world’s first Zika vaccine, the first MERS vaccine, an advanced Ebola Vaccine, and a novel HIV vaccine, among others. Additionally, the Weiner laboratory has helped to develop immunotherapy approaches that are currently in clinical testing for HPV-associated cancer, prostate, liver, and other cancers. The first clinically efficacious therapeutic DNA vaccine for HPV cervical intraepithelial neoplasia (CIN) has moved into a licensure trial (REVEAL). His research has earned him many accolades, including the following limited selection: American Association for the Advancement of Science Fellow (2011); International Society for Vaccines Fellow (2012); NIH Directors Translational Research Award (2011); Top 40 Influential Vaccine Scientist (2014); Stone Family Award for Immunotherapy Cancer Research (2014); Vaccine Nation’s 50 Influential Vaccinologists (2015); Children’s Hospital of Philadelphia Hilleman Lectureship (2015); VIE Outstanding Academic Research Laboratory (2015 & 2016; runner-up in 2017-2019); Top 20 Nature Biotechnology Translational Laboratories (every year from 2016 to 2020); Pennsylvania Life Sciences Excellence Award (2019); President of the International Society for Vaccines (2018-2020); Pennsylvania Drug Industry Award in Scientific Excellence (2022); and the Genscript Outstanding Lab Award (2023).

Weiner received his B.S. in biology from Stony Brook University, N.Y., and his M.S. in biology from the University of Cincinnati. He then earned a Ph.D. in developmental biology with a focus on molecular immunology from the University of Cincinnati, College of Medicine. Weiner joined the University of Pennsylvania as a research fellow in the Department of Pathology and Laboratory Medicine, where he rose through the ranks to become Professor. He held a second appointment from The Wistar Institute from 1990 to 1993. At Penn, he served as co-chair of the Tumor Virology Program of the Abramson Cancer Institute and as chair of the Gene Therapy and Vaccine Training Program before moving to The Wistar Institute full time; he still retains professor emeritus status at Penn.

The Weiner Laboratory

The Weiner laboratory represents one of the pioneering research teams in the field of DNA vaccines and immunotherapies. The lab has published more than 500 scientific papers, chapters and reviews, including many seminal papers in the DNA vaccine and synthetic nucleic acids field, and is credited with generating more than 70 patents. Along with collaborators, the Weiner Lab was the first to move DNA vaccines to human clinical studies, establishing their initial safety and immunogenicity. The team also helped to develop the new field of nucleic acid-encoded antibodies, or dMAbs. More than a dozen experimental clinical therapies and vaccines have been developed from research from the Weiner laboratory, including the first Zika vaccine in clinical trials, the first MERS vaccine, a novel Ebola vaccine as well as novel immunotherapy for HPV-associated cancer and precancer, and a novel immunotherapeutic vaccine for glioblastoma. Other notable reports from the Weiner lab include the first DNA vaccine studied for HIV and for immunotherapy of cutaneous T-cell lymphoma and the early development of DNA-encoded genetic adjuvants, including IL-12.

The Zika virus has become a global health concern due to its rapid spread and concerning link to microcephaly in infants. The Weiner lab has received funding from the Bill & Melinda Gates Foundation for a collaborative project with Inovio Pharmaceuticals and HUMABS BioMed to develop DNA encoded monoclonal antibodies (DMAbs) against Zika. DMAbs are injected into the muscle and the human body is used as its own bioreactor to produce protective antibodies. Working with highly effective antibodies for which sequences were provided by HUMABS, the Weiner lab is optimizing DMAbs for high levels of expression, binding and neutralization. Once these DMAbs are shown to be protective in mice, they will be tested in nonhuman primates and eventually prepared for clinical trials with the assistance of Inovio.

Funded by the Bill & Melinda Gates Foundation, this study addresses the possibility of achieving vaccinal effect by co-delivering DNA-encoded monoclonal antibodies (DMAbs) and synthetic DNA vaccines to prevent HIV infection.

Funded by the Bill & Melinda Gates Foundation, the focus of this study is to develop new synthetic DNA vaccines encoding designed circumsporozoite protein (CSP) antigens to provide a new generation advanced CSP component for a prophylactic malaria vaccine.

The Weiner lab has a long history of working on DNA vaccine for human immunodeficiency virus (HIV). The lab is currently a part of a multi-institutional group working on developing a prophylactic HIV vaccine under a five-year Integrated Preclinical/Clinical AIDS Vaccine Development Program grant from the National Institutes of Allergy and Infectious Disease (NIAID). Working with Inovio Pharmaceuticals, Duke University, Emory University, University of Massachusetts, and the National Institutes of Health, the group aims to build on the success of previous generations of DNA vaccines in order to induce strong cellular and humoral responses. The main focus of the program is inducing broad responses against the diverse HIV surface protein, Env.

The Weiner lab has teamed up with investigators at the University of Pennsylvania to develop a novel vaccine to prevent cancer development in high-risk patient populations. This includes individuals who carry mutations in the BRCA1 or BRCA2 genes and are susceptible to the development of breast, pancreatic and ovarian cancer. This novel vaccine encodes the tumor antigen TERT, which is highly expressed in tumor cells, and is particularly high in tumor samples from patients with mutations in DNA damage repair pathways, such as the BRCA1/BRCA2 pathway. The lab developed this vaccine and is currently working to improve efficacy using combination therapies with immune checkpoint blockade antibodies in mouse models. In parallel, a clinical trial is being conducted for high-risk patients in remission after adjuvant therapy for TERT DNA vaccine with or without IL-12 immune plasmid adjuvant. This project is funded by a Breakthrough Science Team Award through the Basser Research Center for BRCA at the University of Pennsylvania.

Funded by the Department of Defense (DoD), this study will characterize a novel vaccine targeting follicle stimulating hormone receptor (FSHR) in ovarian cancer.

The objective of this study is to support improvements in the immunogenicity and durability of seasonal influenza vaccines, and the development of innovative influenza vaccine approaches that provide robust, durable, broadly protective mucosal and systemic anti-influenza immunity (“universal influenza vaccines”). Research will support iterative vaccine design based on detailed immunologic assessment of influenza vaccine candidates through preclinical animal studies, early phase clinical trials and healthy volunteer human challenge studies, to advance the most promising vaccine candidates into phase 1/2 clinical trials.

Translational Platform Program encompassing cGMP manufacturing and clinical development of DNA vaccine candidates against both Lassa virus and MERS coronavirus, with funding from the Coalition for Epidemic Preparedness Innovations (CEPI).

Funded by the Coalition for Epidemic Preparedness Innovations (CEPI), Wistar will support the development of a synthetic DNA vaccine and nanoparticles against Wuhan coronavirus 2019-nCoV. Successful characterization of the blocking antibody will permit us to explore monoclonal antibody production, engineer the monoclonal antibody into the synthetic DNA-based DMAb platform, and engineer into the nanoparticle platform as potential vaccines and immunotherapeutics against the Wuhan Coronavirus 2019-nCoV.

This NIH-funded study addresses Novel DNA-encoded monoclonal antibodies (DMAbs) for control of antimicrobial tesistant (AMR) Pseudomonas aeruginosa infection.

This NIH-funded study addresses development of a multivalent, DNA vaccine-mediated protection against Tuberculosis.

Villanueva studies the molecular signaling pathways that become deregulated in melanoma with the goal of identifying suitable targets for therapy, particularly for tumors with limited therapeutic options.

Villanueva received her Bachelor of Science degree in biology at Universidad Peruana Cayetano Heredia in her native Peru. She then enrolled in the graduate program at University of Miami School of Medicine and she earned a Ph.D. in Molecular Cell and Developmental Biology. She pursued postdoctoral training at the University of Pennsylvania School of Medicine where she began her research on melanoma. Villanueva joined The Wistar Institute as a postdoctoral fellow in the Herlyn laboratory, and was later appointed assistant professor in the molecular and cellular oncogenesis program.

Meet the Villanueva Lab Team

The Villanueva Laboratory

The Villanueva laboratory is actively studying the molecular mechanisms mediating drug resistance in melanoma, aiming at designing effective therapies that will overcome it. The lab has extensively investigated the role of the RAF/MEK and PI3K/mTOR pathways as therapeutic targets and the mechanisms underlying resistance to inhibitors that block these signaling cascades. More recently, the team is focusing on identifying new targets or vulnerabilities that can be therapeutically exploited in NRAS mutant melanoma, a tumor type in dire need of new treatments.

The focus of the Villanueva lab is to identify novel targets to overcome drug resistance in melanoma.

The Villanueva lab has developed pre-clinical models that show how melanoma gains resistance to BRAF and MEK inhibitors. Using these models, they demonstrated that melanoma cells treated with RAF inhibitors bypass the effects of the drugs by reactivating the MAPK pathway and/or activating alternative signaling pathways, including RTKs, PI3K/mTOR and STAT3. For example, the lab identified a novel MEK2 mutation that, together with BRAF amplification, confers resistance to RAF and MEK inhibitors. Based on these findings, the team tested combination therapies to overcome drug resistance.

NRAS is a poorly characterized RAS family member, and the biology of NRAS mutant tumors remain inadequately understood. There are very limited treatment options for patients carrying NRAS mutations, which are present in more than 25 percent of all melanomas. As targeting NRAS directly has thus far not been possible, the aim of the lab is to eradicate this type of tumors by blocking critical RAS effectors or pathways that are essential for tumor survival. The team has identified several non-oncogene dependencies that are critical for survival of melanoma cells including BRD4, TERT(*) and the ribosomal serine/threonine kinase S6K2. The lab is investigating the role of these dependencies in melanoma and evaluating the impact of blocking their activity on tumor initiation, maintenance and survival using 3-D organotypic spheroids, patient-derived xenograft (PDX) models and syngeneic mouse models.

Watch the animation below to learn more about our strategies to combat NRAS mutant melanoma.

Tempera’s research focus is on the epigenetic mechanisms underlying Epstein Barr virus (EBV) infection to identify new viral functions that can be targeted as novel therapeutic approaches for treating EBV-associated cancers.

Tempera obtained his B.Sc. and Ph.D. degrees from University of Rome “La Sapienza”, Italy. He was a postdoctoral fellow at Wistar and established his laboratory at the Fels Institute for Cancer Research and Molecular Biology at Temple University, where he was promoted to associate professor. In 2020, Tempera returned to Wistar as an associate professor in the Gene Expression & Regulation Program, which became the Genome Regulation and Cell Signaling Program in 2024.

The Tempera Laboratory

Approximately 90 percent of the world population is infected with EBV and carries the virus in a silent state for life. Although EBV infection is asymptomatic in most cases, in some people it can cause infectious mononucleosis. In immunocompromised individuals, such as in HIV-infected persons and transplant recipients, EBV can cause B-cell transformation and malignancies including Burkitt’s lymphoma, nasopharyngeal carcinoma, and Hodgkin’s and non-Hodgkin’s lymphomas. EBV-associated cancers are still treated with chemotherapy, even though they have a specific pathogenic cause, but various attempts are being made to target EBV directly and develop EBV-specific therapies.

One approach to control EBV infectivity is by changing the expression of viral genes. The Tempera lab studies how epigenetics contributes to regulating the gene expression patterns adopted by EBV during latency. They utilize their expertise in genomics and genome-wide data analysis to better understand the link between the three-dimensional structure of chromosomes, chromatin composition and gene expression during EBV latency.

Learn more about the members of the Tempera Lab

EBV-induced malignancies have been challenging to target, in large part because EBV establishes a latent infection with complex and dynamic gene expression patterns. These patterns are referred to as “latency types” and can adapt to diverse host cell types and immunological responses. This dynamic gene expression allows EBV to escape eradication by immune surveillance and persist as a long-term, latent infection. In a series of studies, our group has explored the role of epigenetics in the regulation of EBV latency.

Although a role for epigenetic modifications in EBV has been appreciated for decades, our results over the past years have yielded surprising and important insights into its mechanism. We found that different EBV latency programs correlate with different epigenetic states of the viral episome, and we identified CTCF as the primary cellular factor that regulates these epigenetic patterns. Overall our work shows that:

• The epigenetic regulation of EBV is a dynamic process involving both histone modifications and DNA methylation;
• The CTCF cellular factor is critical for the maintenance of the viral chromatin state of EBV;
• CTCF regulates the viral promoters.

These findings defined the important function of CTCF as a chromatin organizer of the EBV viral genome.

Our team has explored the three-dimensional organization of the EBV genome during latency. Since CTCF promotes chromatin loops in the human genome, we tested the possibility that CTCF acts in a similar way on the EBV genome. By combining 3C assay, ChIP-seq and EBV genetic methods, our group has shown that:

• The EBV genome adopts alternative chromosome conformations during latency;
• CTCF is the critical cellular factor that mediates chromatin loop formation in EBV;
• The viral enhancer at the Ori P region of EBV serves as a “chromatin hub” regulating viral promoters through chromatin loops;
• The disruption of EBV three-dimensional organization impairs viral gene expression.

Our results have important biological implications since they demonstrate for the first time that viral genomes can also regulate their function by adopting different three-dimensional configurations.

We discovered that PARP1 can interact with the EBV genome. PARP1 is a host enzyme that post-translationally modifies proteins through the transfer of ADP-ribose from NAD+ onto acceptor proteins. The role of PARP1 in DNA damage and apoptosis is well characterized; however, in recent years, PARP1 has also been implicated in chromatin modification, transcriptional regulation and inflammation.

Evolutionary analyses have identified other PARP family proteins that likely have evolved a role in host-virus conflicts. Indeed, a body of evidence suggests that PARP1 may serve as a stress sensor — a function that would be especially relevant in regulating herpesvirus lytic reactivation. CTCF is also PARylated by PARP1, subsequently altering its insulator function.

Based on the established role of CTCF in EBV latency, the functional interactions of PARP1 and CTCF, and because CTCF and PARP1 are both implicated as viral restriction factors in other herpesviruses, our group has studied the role of PARP1 in regulating the EBV epigenome.

We have shown for the first time that LMP1 signaling affects important chromatin-modifying enzymes, specifically PARP1. PARP1 regulates global gene expression by relaxing the chromatin structure and inhibiting the accumulation of repressive histone marks.

We discovered that inhibiting PARP1 suppresses malignant transformation in vitro and represses the expression of previously identified LMP1 genetic targets. Thus, our team has explored the hypothesis that PARP1 activity plays an important role in EBV-induced oncogenesis. Current projects in our laboratory aim at establishing PARP inhibitors as a novel target for EBV-induced cancers and determining the pathogenic mechanisms involved in EBV-mediated tumor initiation.

Our group discovered that inhibition of PARP1 activity dramatically changes the expression levels of hundreds of genes, including genes involved in cancer. We found that increased levels of the Polycomb Repressive Complex 2 (PRC2) catalytic subunit EZH2 are responsible for some effects caused by PARP inhibition.

We reported for the first time that:

• PARP1 and EZH2 occupancy negatively correlate across the genome;
• PARP1 can directly modify EZH2;
• PARylation alters the enzymatic activity of EZH2.

Based on these data, our team has explored the hypothesis that PARP1 and PARylation play an important and underappreciated role in EZH2 activity and inhibitors of PARP can alter PRC2-mediated gene repression. We are working to establish PARP1 and PARylation as a novel mechanism of EZH2 regulation and determine mechanisms and functional relevance of PARP-mediated EZH2 inhibition.

Tang applies cutting-edge mass spectrometry-based proteomics to a wide range of biomedical projects to facilitate discoveries that will yield novel insights that are not biased by prior knowledge and have the potential to lead to new scientific directions.

Tang received his formal training in biochemistry and molecular biology through earning his Ph.D. from the Institute of Molecular and Cell Biology in Singapore. In 2000, Tang joined The Wistar Institute as a postdoctoral fellow in the laboratory of Dr. David Speicher and subsequently became the managing director of the Proteomics and Metabolomics Shared Resource. He was promoted to assistant professor in 2022.

The Tang Laboratory

Proteomics contributes to a better understanding of the molecular basis of diseases at the systems biology level, and has the potential to identify new therapeutic targets and potential diagnostic and prognostic biomarkers. The Tang laboratory collaborates with other researchers using state-of-the-art high-resolution mass spectrometry and related experimental strategies to investigate proteome changes and protein posttranslational modifications associated with cancers, such as melanoma, prostate, and ovarian cancers, and other diseases. For some studies, proteomics results are combined with other omics technologies – particularly metabolomics and lipidomics – to provide a more complete picture of the molecular contributors to diseases.

The Tang laboratory is actively involved in multiple collaborative projects that focus on defining disease-related cellular mechanisms and discovering therapeutic targets of diseases. These projects involve diverse experimental strategies that include global proteome profiling, quantification of disease biomarkers, characterization of protein post-translational modifications, identification of protein interactomes, and global polar metabolite and lipid profiling. Results from these analyses have provided insights into mechanisms underlying different cancers such as melanoma, prostate cancer, and ovarian cancer, as well as identified putative biomarkers for disease states.

The Tang laboratory is also involved in improving proteomics technologies in key areas including:

• Chemical crosslink-MS. Chemical crosslinking combined with mass spectrometry (MS) analysis is a powerful method to study protein-protein interaction networks and to obtain valuable structural information from protein complexes. Both traditional non-cleavable and MS-cleavable cross-linkers can be used for identification of protein-protein interaction sites, but MS-cleavable crosslinkers are advantageous because of their ability to generate distinguishing fragment ions during MS/MS that greatly improve identification of crosslinked peptides and crosslinked sites. These diagnostic fragment ions will also reduce the search space during data analysis, allowing the crosslinkers to be used in whole proteome labeling studies. We are interested in developing a robust and reliable workflow for efficient identification of crosslinked sites on proteins using MS-cleavable cross-linkers, such as DSSO and DSBU.
• MS-based glycomics and glycoproteomics. Glycosylation is one of the most abundant post-translational modifications (PTMs) in mammalian cells and is crucial for a wide range of biofunctions. Aberrant glycosylation of proteins has been linked to various diseases, including cancers. The major strength of MS-based analyses is the isolation and fragmentation of analytes to obtain structural information. MS-based glycomics typically consists of the following steps: glycan release by either PNGase F treatment (for N-linked glycans) or β-elimination (for O-linked glycans), glycan enrichment using solid phase separation techniques, glycan derivatization, and LC-MS/MS identification. Global profiling of released glycans has been used to distinguish healthy and disease states. However, information on the protein carriers of glycans and residue site localization is lost after glycan release. The more powerful MS-based glycoproteomics approach that we plan to focus on involves structural analysis of glycopeptides. Protein extracts are proteolytically digested followed by glycopeptide enrichment with subsequent LC-MS/MS analysis. Since the glycan is left intact on the peptide, this method allows the identification of the glycosylated proteins and quantitation of the glycan structures on the glycoproteins.

Shinde is an immunologist with interest in characterizing key factors in the tumor microenvironment and gut microbiome that contribute to the refractory nature of cancer and target them for therapies.

Shinde obtained his D.V.M. from Nagpur Veterinary College, India, and his Ph.D. in immunology from the Augusta University. Before joining Wistar as the first/inaugural Caspar Wistar Fellow, he trained as a postdoctoral fellow in the Tumor Immunotherapy Program at the Princess Margaret Cancer Center in Toronto, Canada.

The Shinde Laboratory

The tumor microenvironment (TME), consisting of stroma, immune cells and extracellular matrix, is a key determinant of cancer initiation, progression and resistance to therapies. Understanding the heterogeneity of the TME and the molecular mechanisms contributing to immune responses is critical to enhance immunotherapy and prevent/overcome resistance. Macrophages are major components of the TME and regulate inflammation, angiogenesis, extracellular matrix remodeling, and T-cell suppression. Alterations in the metabolism of macrophages affect their function. Research in the Shinde lab focuses on characterizing the molecular mechanisms underlying metabolic plasticity in macrophages during tumorigenesis.

Commensal microbiota residing in the gut can also modulate the TME and affect tumor progression and response to therapy. Host, dietary and environmental factors contribute to changes in the microbiome. The lab is also interested in characterizing the healthy/symbiotic or disease-modulating/dysbiotic microbiome and its crosstalk with immunometabolism during disease development.

The first project in our laboratory seeks to understand how host metabolism impacts disease progression and therapy resistance in pancreatic cancer. Tumor metabolism in pancreatic cancer is known to be dysregulated both in neoplastic and in tumor microenvironment (TME) cells, significantly altering immune responses. Metabolic profiling has identified increased plasma levels of branched-chain amino acids (BCAA) in a variety of disorders including pancreatic ductal adenocarcinoma (PDAC). Our new work shows that transcriptional regulators of BCAA oxidation, such as Krüppel-like factors (KLF), are linked to the phenotype of tumor-associated macrophages (TAMs). This project seeks to elucidate the functional implications of KLF biology and BCAA catabolism in TAMs for driving tumor progression and resistance to therapy.

The second project in our lab investigates the connections between gut microbial metabolic pathways and therapy response. Immune responses can be altered by metabolic processes occurring outside the TME, for example, by metabolites produced by gut bacteria. Recent studies show that particular species of gut bacteria influence PDAC outcomes and response to therapy and do so by altering innate and adaptive immunity; however, the specific mechanisms are not clear. This project seeks to identify the metabolic pathways by which the gut microbiome influences antitumor immune responses, impacting PDAC burden and therapy response.

Our studies will have potential clinical impact providing insights into previously unsuspected targets for cancer therapy. More broadly, we expect our findings to shed light on how diet, host metabolism and gut microbiome are linked in shaping immune function and therapy response.

Schug is interested in investigating metabolic adaptation in cancer cells through cell biology, biochemistry, liquid chromatography-mass spectrometry (LC-MS)-based lipidomics, and metabolomics.

After completing his B.S. in biology from Saint Joseph’s University, Schug continued his studies in Philadelphia and earned a Ph.D. in molecular cell biology from Thomas Jefferson University. In 2008, he began his postdoctoral studies at the Beatson Institute in Glasgow, U.K. Schug joined The Wistar Institute in 2016 as an assistant professor. He also holds adjunct faculty positions in the Department of Systems Pharmacology and Translational Therapeutics at the University of Pennsylvania and the Department of Biochemistry and Molecular Biology at Drexel University.

The Schug Laboratory

Alterations in the acquisition and metabolism of nutrients are now firmly recognized as hallmarks of cancer development. Many, if not all, oncogenes and tumor suppressor genes induce metabolic reprogramming in cancer cells through changes in the regulation of enzymes and transporters. These changes are necessary for cancer cells to meet the combined biomass and energy demands for growth and are only satisfied by increased capture and synthesis of cellular building blocks such as sugars, fats, and proteins. In addition, cancer cells often invade other tissues where the availability of certain nutrients is drastically different or grow so quickly that the blood supply, and the accessibility to oxygen and other nutrients that comes with it, becomes scarce. During these conditions of nutrient stress, many cancer cells will adapt and use alternative available resources to survive. As part of this process, we also study the interactions between cancer cells and tumor infiltrating immune cells. The lab seeks to better understand the competition for nutrients in the tumor microenvironment through the study of diet, immunometabolism, and tumor metabolism using LC-MS based approaches.

The Schug laboratory is interested in identifying and therapeutically targeting the metabolic changes that arise during the development of cancer and metastasis. They combine cell biology, biochemistry, metabolomics, lipidomics, and genomics to uncover novel metabolic vulnerabilities in cancer. These targets are then further developed for use as effective therapeutic strategies to improve cancer patient treatment.

Salvino is the first medicinal chemist to join Wistar’s staff, and his work to identify novel small molecule lead compounds provides a strong basis for collaboration with all Wistar researchers.

Salvino has more than 30 years of experience in drug discovery, including early stage hit-to-lead, lead optimization, and preclinical development where several drug candidates have successfully completed human clinical trials, including Entereg®, ADL-101, and Radezolid®. Prior to joining Wistar, Salvino was a professor in the Department of Pharmacology and Physiology at Drexel University College of Medicine. Before that, he held high level positions including vice president, senior director, and director in the biotechnology and pharmaceutical industries of Sterling Winthrop, Rhone-Poulenc Rorer, Aventis, Rib-X Pharmaceuticals, Adolor Corporation, and Cephalon.

Salvino received his Ph.D. in organic chemistry from Brown University and completed postdoctoral training in synthetic and medicinal chemistry at the University of Pennsylvania under the mentorship of K.C. Nicolaou and Ralph F. Hirschmann.

The Salvino Laboratory

Salvino’s research is directed at drug discovery and development. His laboratory focuses on early drug discovery and small molecule tool compounds for in vivo target validation to confirm the pharmacological relevance and “drugability” of a therapeutic target. His lab’s work in medicinal chemistry optimization is focused on the design and creation of new chemical analogs to understand structure activity relationships (SAR) critical for optimizing potency and in vivo efficacy for a lead series. This effort is important to help identify a potential preclinical drug candidate or future therapeutic agent against a new biological target.

Salvino is the Scientific Director of the Molecular Screening & Protein Expression Shared Resource which closely aligns screening capabilities for lead optimization and hit-to-lead activities that are ongoing in his laboratory.

Current projects include compounds blocking HIV and other antivirals, glutamate transporter (EAAT2) stimulators, ACSS2 Inhibitors, Proteolysis Targeting Chimeras (PROTACs) with a focus on CDK6, Mdm2, and Tert degraders, small molecules targeting protein-protein interactions, chemical probes for assay development, and cancer targeting and gram-negative bacteria targeting pro-drugs.

Patel researches next generation solutions for emerging infectious diseases, including DNA vaccines and DNA-encoded monoclonal antibodies.

Patel holds a B.Sc. in microbiology & immunology from McGill University, Canada, an M.Sc. in Medical Microbiology from London School of Hygiene & Tropical Medicine, University of London, U.K., and a Ph.D. in medical microbiology from the University of Manitoba, Canada. She received postdoctoral training at the San Raffaele Telethon Institute for Gene Therapy, Milan, Italy, the University of Pennsylvania and The Wistar Institute. She was promoted to research assistant professor at The Wistar Institute Vaccine & Immunotherapy Center; named a Caspar Wistar Fellow in 2020; and promoted to Assistant Professor in 2023.

The Patel Laboratory

The Patel laboratory focuses on vaccine and immunotherapy development against emerging infectious diseases, including study of immune mechanisms that contribute to protection from pathogens. Research in the lab employs non-viral DNA vectors for vaccine and antibody delivery. Patel’s most recent studies include DNA vaccine development against Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and multiple studies in the rapidly advancing field of DNA-encoded monoclonal antibodies (DMAbs). Her preclinical animal studies have led to the successful clinical translation of anti-Ebola virus GP DNA vaccine and anti-Zika virus DMAb candidates (NCT03831503). Patel is part of a team at the Wistar Vaccine & Immunotherapy Center leading preclinical immunological studies of a SARS-CoV-2/COVID-19 DNA vaccine candidate. This vaccine candidate entered the clinic in about 10 weeks from vaccine design to FDA approval and trial initiation (NCT04336410 and NCT04447781).

Patel’s most recent studies include DNA vaccine development against Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Emerging respiratory pathogens including influenza A/B viruses and seasonal coronaviruses, as well as antimicrobial-resistant bacteria are also of interest. In addition to vaccine development, the lab studies potential correlates of protection (antibodies and T cells) in non-human primate samples to improve vaccine development and efficacy and bridge results from animal studies with human clinical data.

Nucleic acid gene-encoded antibodies are a rapidly advancing field. Patel’s preclinical animal studies have led to the successful clinical translation of an anti-Zika virus DMAb candidate (NCT03831503). The lab’s research interests include approaches to improve DMAb protective efficacy through sequence engineering and strategies for effector function/immune cell recruitment. This includes understanding ways to modulate the early innate immune responses against DNA vectors to improve long-term duration in vivo. These studies could have interesting implications for both infectious diseases antibody delivery as well as different gene therapy approaches.

Nefedova’s research focuses on understanding molecular mechanisms by which the bone marrow microenvironment promotes tumor survival and progression.

Nefedova obtained her M.D. and Ph.D. degrees at the Pavlov State Medical University of St. Petersburg, Russia. She then pursued postdoctoral training at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, FL, where she began her research in multiple myeloma. In 2013, Nefedova joined The Wistar Institute as an assistant professor in the Tumor Microenvironment and Metastasis program, and was promoted to associate professor in the Immunology, Microenvironment and Metastasis Program in 2017. She joined the Molecular and Cellular Oncogenesis Program in 2024. 

The Nefedova Laboratory

The Nefedova laboratory focuses on understanding the role of the bone marrow microenvironment in regulating tumor progression and therapy resistance. The laboratory primarily studies multiple myeloma, a cancer of plasma cells that localizes in the bone marrow.

The laboratory is interested in mechanisms by which interactions between neutrophils in the bone marrow and multiple myeloma cells promote disease progression and chemoresistance. They are investigating the implication of neutrophil extracellular traps (NETs) — structures composed of chromatin and neutrophil proteins — in myeloma progression, and targeting a process of NET formation for treatment of multiple myeloma. The laboratory is also interested in the role of the S100A9 protein, highly expressed by neutrophils, in the pathogenesis of multiple myeloma.

Liu applies biostatistics, the statistical analysis of complex data generated through modern biological approaches and clinical information, to find correlations between biomarkers, disease and individual patient health.

Liu earned a medical degree and a master’s degree in health statistics at Shanxi Medical University in Taiyuan, China. She obtained a Ph.D. in biostatistics at Shanghai Medical University in Shanghai, China in 1998. She then completed a postdoctoral fellowship in biostatistics and epidemiology at the University of Massachusetts. While there, she earned a second master’s degree in public health and epidemiology. In 2005, Liu was appointed assistant professor in the Department of Cancer Biology at the University of Massachusetts Medical School (UMMS). Two years later, she joined the Biostatistical Research Group in the Division of Preventive and Behavioral Medicine and served as an assistant professor of Biostatistics in the Department of Medicine at UMMS. Liu joined The Wistar Institute in 2011 as an associate professor and was promoted to professor in 2017.

The Liu Laboratory

The Liu laboratory applies biostatistics to several areas of research, including: basic cancer research and clinical trials of cancer immunotherapy; infectious diseases; behavioral and educational intervention research; and research on health care outcomes.

The Biostatistics Unit supervised by Liu provides in-house biostatistics expertise to accommodate continuing growth in translational and pre-clinical cancer research. This Unit provides statistical support to biological laboratories at Wistar and its tasks include, but not limited to, large data management, experiment design, statistical data analysis, data presentation for manuscripts and grant proposal development. Liu has extensive experience working with basic and clinical investigators on statistical issues. Her strong statistical and biomedical backgrounds have enabled her to provide exceptionally high levels of scientific input to different projects. As a result, her effort has contributed to many published papers and funded grant proposals for clinical and basic science investigators. Within a short time after she joined The Wistar Institute, she engaged in a plethora of collaborative projects with Wistar Cancer Center members and obtained joint NIH funding with inside and outside Wistar investigators, including two P01 Program Project grants on novel molecular therapies of prostate cancer and melanoma targeted therapies. There is significant institutional support for collaborative efforts between the Biostatistics Unit and the investigators at Wistar.