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My research interests are in translational science. Specifically, I am interested in designing early-phase clinical trials based on an improved understanding of tumor immunobiology and host-tumor-microenvironment interactions. Additionally, I am interested in the mechanisms underlying non-response to checkpoint inhibition and novel approaches to overcome this non-response. My clinical interests are in the management of advanced melanoma and the development of early phase studies to test novel immunotherapeutic approaches singly and in combination in patients with advanced cancer.
Dr. Edwards' research interests include the treatementHPV-related and ovarian malignancies with immunotherapeutic approaches. He serves as principal investigator for a number of pharmaceutical-sponsored studies. He also serves on the Cancer Vaccine Committee, which experiments with novel therapeutic approaches to gynecologic malignancies and produces translational research.
Three specific targets of Dr. Edwards' research include: 1) vaccine therapies for cervical and ovarian cancer; 2) combining biologic and immunologic therapies with traditional therapies in the treatment of women's cancer; and 3) intraperitoneal therapy.
Dr. Falo is actively involved in a variety of research projects focused on the prevention and treatment of melanoma and skin cancers, and has research expertise in the areas of cutaneous drug delivery, radioprotection, immunobiology, vaccine design, antigen processing and presentation, dendritic cell biology, and molecular immunobiology and immunotherapy.
Dr. Ferris's laboratory is focused on understanding basic immunological mechanisms of the lymphocyte response to cancer,including T cells and natural killer (NK) cells, for the development of novel immunotherapeutic approaches to head and neck cancers (HNC). Tumor immunotherapy and vaccine clinical trials are currently underway and new strategies are in development, focused heavily on neoadjuvant “window of opportunity” trials. We are particularly interested in the immune response to a distinct subgroup of head and neck squamous cell carcinomas caused by human papillomavirus (HPV). Monitoring the successful immune effects of individuals treated with immunotherapy is a major effort, using single cell transcriptomic, proteomic, spatial technologies. We are also studying tumor induced immune evasion, such as defective antigen processing/presentation and alternative immune checkpoints to subvert T lymphocyte recognition of tumors. Our studies are funded by multiple NCI R01 and SPORE grants as well as extensive collaborations with biotech and pharma to investigate mechanisms of therapeutic activity or resistance to clinically available immune-oncology (I-O) agents currently in the clinic. Validation in animal models is a parallel effort once mechanism(s) are identified in clinical specimens of I-O treated patients.
As Director of the Solid Tumor Cell Therapy Program at UPMC Hillman Cancer Center, I oversee both clinical and research studies aimed at developing effective T cell-based immunotherapies for advanced cancer. We employ an integrated translational approach based upon preclinical in vitroexperimentation, in vivo murine models, and informative human clinical trials. The analysis of clinical results feeds further basic experimentation in an iterative process aimed at elucidating important immunologic principles for the successful treatment of human cancers.
Dr. Kirkwood’s research focuses upon melanoma immunobiology, therapy and prevention. His translational studies established the first effective adjuvant therapy of melanoma, and identified the immunological basis of this therapy, and are now probing the role of molecularly targeted agents (BRAF, MEK, and PI3Kdelta/gamma inhibitors) that may improve upon the efficacy of anti-PD1 immunotherapy, both in advanced melanoma and in the adjuvant operable high-risk melanoma settings. He has advanced the multimodal therapy of melanoma with surgery, stereotactic radiotherapy, and molecular antitumor agents, displacing chemotherapy in the management of melanoma. He is now pioneering novel clinical trial designs to assess the myriad potential combinations of recently-approved molecular and immunological therapies that are anticipated to be the focus of translational clinical research trials in melanoma for the next decade.
His laboratory is engaged in the molecular and immunohistological analysis of tissues obtained from local institutional, regional, national, and international trials of new therapy. Tumor tissues from patients participating in new modalities and combination therapies, neoadjuvant trials, and prevention interventions are probed using current immunopathological and molecular assessments of signaling pathways, and immune responses to melanoma. Dr. Kirkwood initiated the Biospecimen Repository of the Melanoma and Skin Cancer Program (1996-present, 7,000+ specimens) funded initially through his Specialized Program of Research Excellence 2008-2019, and more recently an endowment that have been promoted research by investigators within and outside the University of Pittsburgh, the Regional Melanoma Translational Research Consortium, the National Clinical Trials Network and the International Melanoma Working Group.
Jason J. Luke, MD, FACP, is an Associate Professor of Medicine at the University of Pittsburgh and UPMC Hillman Cancer Center where he is Associate Director for Clinical Research and the Director of the Immunotherapy and Drug Development Center (Phase I). Dr. Luke specializes in early phase drug development for solid tumors (particularly novel immunotherapeutics and biomarkers of immunotherapy activity) as well as the management of melanoma.
Dr. Luke is one of the foremost international investigators in the realm of immuno-oncology, having led clinical trials of immunotherapies including but not limited to anti-PD1/L1, CTLA4, many secondary checkpoints, bispecific approaches (checkpoint, CD3 and cytokine), metabolism modifiers (IDO, A2Ar/CD73/CD39 and arginase), innate agonists of STING, TLRs and oncolytic virus as well as solid tumor cellular therapies (TCRs and CART). In melanoma, Dr. Luke has designed and led two practice changing trials determining the role of anti-PD1 + CTLA4 after initial anti-PD1 failure (compendium listed in the NCCN) and altering the landscape of melanoma oncology practice across dermatology, surgery and medical oncology via establishment of modern adjuvant therapy with anti-PD1 for node negative stage IIB/C disease (leading to FDA/EMA approval). Dr. Luke has been a major contributor toward the investigation of radiation and the microbiome in relation to cancer immunotherapy. Dr. Luke’s major translational research focus leverages large scale informatics to advance cancer immunotherapy.
Dr. Luke received his MD from Rosalind Franklin University of Medicine and Science in Chicago. He then pursued internship and residency at the Boston University Medical Center followed by medicine and medical oncology fellowships at Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center in New York City. Following fellowship, Dr. Luke was a tenure-track, Type 1 Instructor in Medicine at Harvard Medical School as well as Staff Physician at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston. Thereafter Dr. Luke was an Assistant Professor at the University of Chicago.
Dr. Luke is currently Senior Editor at Clinical Cancer Research, Section Editor at the Journal for Immunotherapy of Cancer and Skin Cancer Section Editor for the American Cancer Society journal Cancer. Dr. Luke is actively involved in several professional societies including SITC (where he sits on the Board of Directors), AACR, ASCO, and the Society for Melanoma Research, having served on the scientific program committees for each. Dr. Luke leads an R01 funded laboratory, he is co-PI for the Pittsburgh UM1 LAO and is project 3 clinical co-leader of the Pittsburgh Skin Cancer P50 SPORE, in addition to multiple private and state awards. Dr. Luke has received several awards for research and clinical care including the Melanoma Research Foundation Humanitarian Award, Crain’s 40 under 40, DOD Career Development Award, Paul Calabresi Career Development in Clinical Oncology Award (K12), ASCO Merit Award as well as Young Investigator Awards from the Melanoma Research Alliance, the Cancer Research Foundation and the Conquer Cancer Foundation of ASCO.
Yana G. Najjar, MD is a translational investigator and cutaneous oncologist at the UPMC Hillman Cancer Center, where she is an Assistant Professor of Medicine and Director of the Clinical and Translational Research Center. Dr. Najjar specializes in the treatment of advanced melanoma, focusing on anti-PD1 resistant melanoma and rare melanoma subtypes. Using a bench-to-bedside approach, she has developed multiple investigator-initiated trials that aim to remodel melanoma tumor cell metabolism and hypoxia in the tumor microenvironment to overcome mechanisms of resistance to immunotherapy. Her lab is focused on various correlative analyses from investigator-initiated trials. Dr. Najjar's research is funded by the NIH, the Department of Defense and the Melanoma Research Alliance.
Prior to joining the faculty of the Department of Neurological Surgery at the University of Pittsburgh in 1992, Dr. Ian Pollack was awarded the 1991 Van Wagenen Traveling Fellowship, which afforded him a year of subspecialty training in the Department of Neurosurgery at the Hospital for Sick Children in Toronto, the Neuro-Oncology Laboratory of the University of Lausanne in Switzerland, and the Laboratory of Tumor Biology of the University of Uppsala in Sweden. Dr. Pollack graduated magna cum laude from Emory University in 1980, where he earned a BS degree in chemistry. He received his medical degree from the Johns Hopkins University School of Medicine in 1984, then completed a surgical internship and neurosurgical residency at the University of Pittsburgh School of Medicine. Dr. Pollack has published more than 400 papers in refereed journals, numerous book chapters and invited papers, and has edited two books on childhood brain tumors. He is co-editor of the recently published book Principles and Practice of Pediatric Neurosurgery and an accompanying atlas Operative Techniques In Pediatric Neurosurgery. He is currently a principal investigator on numerous NIH and foundation grants focusing on novel therapies for brain tumors and evaluating molecular markers of tumor resistance to therapy. He chaired the CNS Tumor Committee of the Children's Oncology Group from 2000 to 2009, co-chaired the National Cancer Institute Brain Malignancy Steering Committee from 2010-2017, is on the Executive Committee of the NCI-Funded Pediatric Brain Tumor Consortium, and is the immediate Past-Chair of the American Board of Pediatric Neurosurgery.
Our research focuses on various aspects of T cell regulation and function:
(1) Mechanistic Focus:
(a) Immune Regulation: Regulatory T cells (Tregs): Identification of novel Treg molecules and their function; mechanism of Treg function; regulation of Treg stability via Nrp1 and other pathways; IL-35 signaling and mechanism of action; novel Ebi3 binding partner; IL-10 & IFNy function; neuron-immune interactions.
(b) Immune Regulation: Inhibitory Molecules: Identification of novel inhibitory receptors (IR) and their mechanisms; immune modulation of T cell subsets by LAG3; PD1 and NRP1; PD1-LAG3 synergy; mechanism of CD8+ and CD4_ T cell exhaustion; protein engineering to develop novel therapeutics.
(c) Structure-function analysis of T cell receptor (TCR):CD3 complex and LAG3 signaling: Mechanism of TCR:CD3 signaling; modulation & control of TCR signaling by IRs.
(d) Systems Immunology: Single cell systems approaches (transcriptomic & epigenomic) to hypothesis test, hypthesis generate and discover; technology and algorithm development; multispectral imaging.
(2) Disease Focus:
(a) Cancer: Biology of LAG3/PD1, IL-35 and NRP1 in mouse models of cancer and also in samples from treatment-naive patients or immunotherapy recipients; primary focus on solid tumors – head & neck, melanoma, lung, ovarian, breast cancer, with some work on pancreatic, GI and glioma cancers, and pediatric solid malignancies; novel approaches for therapeutic translation; biomarker discovery.
(b) Autoimmune and Inflammatory Disease: Impact, function & insufficiency of Tregs and IRs in several autoimmune and inflammatory disease with emphasis on models of autoimmune diabetes (NOD), EAE and asthma; development of therapeutic approaches (enhance Treg stability; IR agonists.
Hassane Zarour, MD is a dermatologist and cancer immunologist whose research focuses on basic and translational human cancer immunology in the melanoma field. His work has led to the identification of novel melanoma MHC class II-presented epitopes that have been used in investigator-initiated trials at UPMC Hillman Cancer Center as well as in multi-center trials. Most recently, Dr. Zarour's work has contributed to elucidating the role of inhibitory receptors in promoting melanoma-induced T cell dysfunction in the tumor microenvironment. These findings led to the development of novel antibodies targeting inhibitory receptors for clinical trials. Dr. Zarour actively contributes to the design and the implementation of novel investigator-initiated trials based on laboratory findings, including two melanoma vaccine trials funded by the Cancer Research Institute and the National Cancer Institute, respectively. He is the lead scientific investigator on the Hillman Skin Cancer SPORE Project 3 that is testing the novel combination of BRAF inhibitor (BRAFi) therapy with high-dose interferon for metastatic V600E positive melanoma. He is also testing a novel combination of an anti-PD-1 antibody (MK 3475/Pembrolizumab) and PEG-interferon with grant support from an academic-industry award of the Melanoma Research Alliance.