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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 cervical and ovarian malignancies. He serves as principle investigator of the Gynecologic Oncology Group for the University of Pittsburgh and 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 T lymphocyte response to cancer, for the development of novel immunotherapeutic approaches to head and neck cancers (HNC). Tumor vaccine clinical trials are currently underway and new strategies are in development. We are particularly interested in the immune response to human papillomavirus (HPV)-associated head and neck cancer, which appears to be a distinct subgroup of head and neck squamous cell carcinomas. Monitoring the successful immune effects of individuals treated with immunotherapy is a major effort, in order to develop improved generations of vaccine approaches. We are also studying tumor induced immune evasion, such as defective antigen processing and presentation to subvert cytotoxic T lymphocyte recognition of tumors.
Another area of study involves the promotion of tumor metastasis by a family of molecules called chemokines. We are finding important roles for chemokine receptors in cancer metastasis. These chemokines are small, secreted molecules that mediate homing and recruitment of immune cells in response to inflammation, through a family of G-protein linked receptors. Overall, these studies are designed to identify the chemokines relevant to progression of HNC and to provide initial data on their possible clinical utility as components of future vaccination therapies for HNC. In addition, our group is interested in developing immune/inflammatory biomarkers present in the bloodstream for HNC detection, and monitoring in populations at risk for cancer recurrence and/or second primary tumors.
The Kirkwood laboratory is engaged in the study of melanoma immunobiology, and the assessment of multiple new immunomodulators in the context of trials conducted by the Hillman Melanoma Program, and the SPORE in Melanoma and Skin Cancer, as well as the International Melanoma Working Group. The study of predictive and prognostic biomarkers of melanoma complements the studies of molecular inhibitors of melanoma signaling and immunomodulatory agents given alone and in combination with one another.
I am Associate Professor of Medicine at the University of Pittsburgh Medical Center and Director of the Cancer Immunotherapeutics Center at Hillman Cancer Center who focuses on translational therapeutic advances for malignant melanoma and early phase drug development for advanced cancers. I have particular expertise in the immunotherapy of cancer, having been a lead investigator for immunotherapies such as anti-PD1/L1, CTLA4, LAG3, TIM3, GITR, OX40, CD137, CD40, inhibitors of indolamine-dioxygenase, adenosine A2a receptor & arginase as well as agonists of STING & oncolytic virus. I maintain an on-going interest in the molecular biology of cancer and particularly in the intersection between oncogene targeted small molecules and immunotherapy. I have pursued large scale biobanking efforts surrounding cancer immunotherapy and am interested in identifying tumor-intrinsic mechanisms of immune exclusion from patient samples by employing multi-omic bioinformatic approaches. I have been successful in obtaining independent support for clinical investigation from private, public and industry sources.
I aim to advance the treatment of melanoma by complementing clinical care with the principles of translational science. Specifically, my research focuses on immunotherapy in advanced melanoma and its impact on the tumor microenvironment and the peripheral immune system. My goal is to develop rational combinations of immunotherapy, targeted therapy and other agents that may potentially remodel the tumor microenvironment in order to render it less hostile to the host immune system.
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 250 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 grants focusing on novel therapies for brain tumors and evaluating molecular markers of tumor prognosis. He has co-chaired the National Cancer Institute Brain Malignancy Steering Committee since 2010.
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.