Investigators

Summary

To identify molecular differences between responders and non-responders in cancer immunotherapies, we develop data-science techniques, AI-driven tools, and statistical inference methods. Based on the models, we attempt to stratify patients that will likely benefit from immunotherapies and identify potential therapeutic agents in collaboration with Drs. Hassane Zarour, Kathy Shair, and Masa Shuda.

Summary

My current cancer-related research is focused on i) RB1 tumor suppressor and ii) nutrient interventions that may suppress tumor growth.

RB1 is a tumor suppressor gene that is inactivated in a significant proportion of all cancer cases. A therapeutic approach that specifically targets defects in this tumor suppressor is currently not available. A synthetic lethal (SL) interaction occurs between two genes when the inactivation of either gene alone is viable but the inactivation of both genes simultaneously results in the loss of viability. My lab uses a cross-species approach to identify evolutionarily conserved SL targets for RB1-deficient cells. Our focus is to translate our findings from Drosophila screening and from bioinformatics analysis of human cancer cell lines and human cancer patients into appropriate mouse cancer models and ultimately in a clinical trial in human cancer patients.

Summary

Prostate cancer and benign prostatic hyperplasia are two diseases which present a significant burden for older men in the US. Although BPH is not usually life-threatening, the mechanisms contributing to BPH are largely unknown which makes it difficult to develop successful BPH prevention and treatment strategies. My research focus is developing and characterizing animal models of BPH and prostate cancer as powerful tools for measuring efficacy of small molecules designed to inhibit androgen receptor function in prostate cancer and of 5ARI and COX-2 inhibitors to reduce prostatic inflammation and improve bladder function in BPH.

Summary

I am a physician-scientist in the Department of Radiation Oncology here at Hillman. The focus of my translational research lab is on the development of new combination radiation immunotherapy treatments. In particular, my current research focus is on the development of targeted radiopharmaceutical therapies to enhance efficacy of immune checkpoint blockade in a variety of cancer models. I currently serve as an Authorized User for the In Vivo Imaging Core Facility and have developed several collaborations with investigators in Hillman. Moreover as a clinician, I treat GU, breast, and cutaneous malignancies and I am involved in translational clinical trials. As a member of the cancer center, I hope to foster collaborations within my clinical department in Radiation Oncology with the greater Hillman community for translational research.

Summary

Dr. Perkins has been continually funded by NIH since 1986 to conduct research focused largely on two broad “themes”. One emphasizes translational studies, drawing on preclinical findings to examine acute effects of nicotine (and cigarette smoking) that may explain persistence of tobacco dependence in humans. That work was recognized in 2020 by American Psychological Assoc’s (APA) Med-Associates Brady-Schuster Award for outstanding behavioral research in psychopharmacology or substance abuse. The second theme aims to improve clinical treatments for smoking cessation. His recent focus has been on development, validation, and extension of an efficient crossover study design procedure to evaluate whether new medications are, or are not, efficacious for helping smokers quit, thereby informing subsequent large and formal randomized trials to confirm such efficacy. Relatedly, he co-authored a smoking cessation treatment guide for health care providers, “Cognitive-behavioral therapy for smoking cessation: a practical guide to the most effective treatments.”  For this work, he was named by the Society for Research on Nicotine and Tobacco (SRNT) as 2022 recipient of the triennial Ove Ferno award for groundbreaking advances in clinical research on nicotine and tobacco use. Today, Dr. Perkins is author of nearly 300 publications, with a citation index (h) above 75 and nearly 20,000 total citations.  He was also elected SRNT president in 2001 and a Fellow of APA, SRNT, and the Society of Behavioral Medicine (SBM).  Finally, he has contributed to the missions of the Univ of Pittsburgh medical school and Psychology department by teaching and mentoring graduate students and medical students. 

Summary

My research focuses on understanding how immune cells integrate signals encountered in the environment to drive functional outcomes at the molecular and epigenetic level in both health and disease. The tumor microenvironment plays important roles in limiting T cell function and anti-tumor immunity. Our lab is exploring how the tumor microenvironment drives T cell dysfunction by altering the T cell epigenome and transcriptome. We use cutting-edge Next-generation sequencing technologies to interrogate the epigenome of T cells in murine models and patient samples. We aim to engineer the T cell epigenome to create better T cell therapies for cancer.

Summary

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.

Summary

I have conducted behavioral research in a variety of cancer populations including breast, gynecologic, head and neck, and hematological malignancies. I currently hold an NCI K23 Career Development Award examining adherence to the medical regimen for hematological cancer patients who are post allogeneic hematopoietic cell transplantation (HCT) and their family caregivers. Allogeneic HCT is a potentially curative therapy for hematologic disease, but is associated with multiple complications and significant stress to patients and family caregivers (CGs). To enhance outcomes and minimize risks, patients and CGs must work together as a team to carefully adhere to the multi-component post-HCT medical regimen, consisting of multiple daily medications, frequent clinic visits, strict catheter care, health monitoring, and dietary and lifestyle restrictions. Despite the clinical importance of adherence to the post-HCT regimen, particularly during the critical first 100 days post HCT, little research has examined rates or risk factors for nonadherence in this population, or how HCT patients and family caregivers manage each component of the post-HCT regimen together. Further, it is important to develop strategies to help patients and family caregivers better adhere to the regimen. Problem-Solving Therapy (PST), an evidenced-based clinical intervention to enhance coping strategies, will be the basis to build a novel patient-caregiver dyadic intervention for the HCT population.

Summary

My current research is in the field of exercise oncology. My focus is the development, use, and implementation of exercise for cancer prevention, control, and survivorship. I am also interested in using dissemination and implementation science to expand exercise services in clinical care. I have largely focused on developing and evaluating exercise interventions for their impact on functional and patient-centered outcomes in adults with cancer. I have worked on several clinical trials that have explored the effect of exercise during different time points along the cancer care continuum. Specifically, I have worked with women with breast cancer prior to surgery and adults with hematologic malignancies scheduled for hematopoietic stem cell transplant. I have also worked with a large variety of solid tumor patients during active chemotherapy and chemoradiation therapy. Currently, I am working to expand my research portfolio by concentrating on developing pre-surgical exercise interventions, or “prehab”, that integrate into the clinical workflow to help ensure patient adherence and healthcare provider support.

Summary

Glioblastomas are highly invasive primary tumors with poor prognosis despite current therapies. Individual targeted therapies have failed to offer long-term survival benefits, although combinations of rationally selected inhibitors may have significant therapeutic applicability for these tumors. Studies by our group and others have also shown aberrant, constitutive activation of NF-kB and Akt as common features of malignant gliomas, supporting their functional role in contributing to apoptosis resistance and refractory growth despite cytotoxic chemotherapy, irradiation, and molecularly targeted therapies. This activation may in part reflect deletions of NF-kB inhibitor-alpha, a common alteration in malignant gliomas, dysregulated stimulation by cell surface tyrosine kinases, such as EGFR and PDGFR-alpha, which are amplified in molecular subsets of malignant gliomas, and mutations in PTEN and other molecular targets that drive Akt and NF-kB activation. Thus, new therapeutic approaches are urgently needed. We have demonstrated that inhibition of NF-kB, Akt, and Bcl-2 may constitute a promising strategy to enhance the efficacy of conventional therapies, such as irradiation and cytotoxic chemotherapy, and potentiate the activity of agents targeted against growth signaling mediators.

Summary

 Dr. Prochownik is interested in cancers resulting from the de-regulated expression of the c-Myc oncoprotein. He is using animal models of pediatric and adult liver cancer (hepatoblastoma and hepatocellular carcinoma) to ascertain the molecular, biochemical and metabolic changes that accompany tumor progression, regression and recurrence. He is utilizing over-expression and knockout models to determine how genes that cooperate with or are affected by Myc such as ChREBP and pyruvate dehydrogenase specifically contribute to the metabolic and molecular landscapes of these tumors.

Summary

My research emphasis is on developing novel artificial and intelligence (AI) tools for enabling non-invasive, quantitative, and accurate assessment of pathological conditions, ultimately advancing a deeper understanding of the underlying mechanism of diseases and facilitating the development of efficacious therapy methods.