Investigators

Summary

Dr. Valerian E. Kagan is one of the world’s recognized leaders and one of the most prominent authorities in the field of Free Radical Biology and Medicine. Internationally known for his profound interdisciplinary studies of oxidative stress, antioxidants, tissue, and cell acute and chronic injury, he has founded a new field of research “Oxidative Lipidomics” and demonstrated its research power in investigations of cell death mechanisms. Free radicals, lipid peroxidation and oxidative stress have been long associated with tissue and cell damage through yet not well…

Summary

My research is focused on human cytomegalovirus (aka "CMV" or "HCMV"), a large, enveloped dsDNA virus in the herpesvirus family. Like all herpesviruses, CMV infects the host for life, and approximately 50% of Americans are infected. CMV is an expert modifier of cellular pathways relevant to cancer-- for instance, it encodes a protein serine-threonine kinase called UL97 that phosphorylates and inactivates the retinoblastoma tumor suppressor protein (pRB). CMV has been implicated in glioblastoma as well as pediatric acute lymphoblastic leukemia (ALL). Nonetheless, I am most excited about the…

Summary

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…

Summary

My lab’s cancer research is to determine if radioprotectants instilled in the urinary bladder prior to irradiation of pelvic or prostate tumors can protect against radiation cystitis without dampening treatment efficacy. We utilize a mouse model of prostate cancer using orthotopic injections of androgen resistant RM-1 and androgen sensitive MyC-CaP cells. Mitochondrial targeted free-radical scavengers are instilled into the bladders of these mice using novel infrared guidance method; assuring the instillate enters the bladder and not the prostate. Fractionated irradiation is used following…

Summary

My lab is currently pursuing several projects:1. The role of TIM-3 in CD8+ T cells This project currently involves the study of - TIM-3, a novel protein of the T cell immunoglobulin and mucin domain family in regulation of CD8+ T cell function during viral infection (using LCMV as a model system) and responses to syngeneic tumors. We are also interested in elucidating signaling pathways downstream of TIM-3.2. The role of TIM-3 in regulatory T cells (Treg)Work from our lab and others has shown that expression of TIM-3 is associated with acquisition of a more potent "effector" Treg (eTreg)…

Summary

As an assistant director of outcomes research, my mission is to assess the value(s) of various treatments and clinical outcomes for cancer care via these tasks below: 1. Establish the infrastructure by collaborating with multi departments for outcomes analyses for cancer treatments. 2. Perform Cost effectiveness analyses and health economics in cancer treatments. 3. Assess various treatment and planning techniques that increase quality and outcomes in cancer care. 4. Serve as NRG oncology physics subcommittee for national clinical…

Summary

Dr. Kinchington’ s research program focuses on the biology of the human alpha-herpesvirus Varicella Zoster Virus (VZV) and its interaction with human neurons and skin using novel model systems. VZV causes Chickenpox upon primary infection, but then remains with the host for life in a latent state in sensory neurons. When the Virus reactivates, it causes Herpes Zoster or Shingles, a painful and debilitating disease that causes significant human morbidity and long-term consequences. Chief among those is the development of long-term, intractable and debilitating chronic pain called…

Summary

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…

Summary

We are currently studying FR901464, a natural product that regulates cancer-related genes by modulating splicing factor 3B subunit 1 (SF3B1) and PHF5A. This compound inhibits cancer proliferation at concentrations as low as 1 nM. To study FR901464, we completed a chemical total synthesis of this natural product. Our synthetic analogs of FR901464, meayamycins, inhibit tumor growth at 10 pM. Additionally, we develop fluorescent probes to gain spatiotemporal insights into hydrogen peroxide, copper ions, and platinum…

Summary

How do different organs and tissues arise? What are the genetic and epigenetic mechanisms that drive this development? To address these questions, we design statistical methods and algorithms and apply them to large-scale, genome-wide data. Ultimately, our goal is to generate, test, and confirm hypotheses that are relevant to human health. Current projects include methods for biology at single cell resolution, disease-specific variant prioritization through non-coding regulator loci, and embryonic development of the heart and…