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An NCI-designated Comprehensive Cancer Center, affiliated with the University of Pittsburgh School of Medicine
Research
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Radiation therapy and many chemotherapies induce DNA damage. These therapies work because cancer cells divide more rapidly than normal cells and cancer cells acquire mutations that change their DNA damage responses and DNA repair mechanisms. Nevertheless, radiation and DNA damaging chemotherapies may not generate long-term responses as the dose of DNA damage required to kill all cancer cells may kill too many normal cells – dose limiting toxicity. The Bakkenist Lab studies how pharmacologic DNA damage response inhibitors can be used to increase the damage induced in cancer cells and potentiate anti-tumor immune responses. Our long-term goals are to develop new therapeutic approaches to manage human cancer.
Visit the Bakkenist Lab Website to learn more.
Research in the Brieno-Enriquez lab focuses on the regulation of gametogenesis in human and mouse and, more specifically, the fundamental mechanisms that are required to produce viable germ cells. Our studies include the analysis of all the different stages of germs cells including primordial germ cells (PGCs), spermatocytes, oocytes, as well as how age affects them. Our long-term goal is to test our overarching hypothesis that gene expression, epigenetic clock, and chromatin structure in the naked mole-rat can be hijacked for use in other species, allowing us to regulate the establishment and maintenance of the ovarian reserve, oocyte quality, and reproductive longevity.
Dr. Greenberger is examining the use of manganese superoxide dismutase (MnSOD) plasmid liposome gene therapy and GS-nitroxides, and other new second generation probiotics LR-IL22 and LR-IFN-B as agents to protect the normal tissues in the esophagus and lung from damage during radiation therapy. Damage to normal tissues during radiation therapy has been a major limitation to the effective treatment of lung cancer. The goal of his research is to improve the quality of life for cancer patients by potentially allowing the use of higher doses of radiation or chemotherapy to effectively treat lung cancer without the damaging side effects.
The O’Sullivan lab at UPMC Hillman Cancer Center conducts research into proteins that alter the structural and epigenetic functions of human telomeres. Telomeres are structures at the ends of chromosomes – the integrity of telomeres is an important factor in maintaining genome stability to prevent cancer and accelerated aging. Current efforts in the lab relate to: (i) deciphering the relationship between the regulation between chromatin structure and telomere function and (ii) new aspects of ADP-ribosylation in genome stability.
My lab studies DNA damage and repair at telomeres. Telomeres are the caps at chromosome ends that are essential for preserving the genome. When chromosomes lose their telomere caps the cells age and this contributes to the onset of degenerative diseases with aging. If chromosomes lose their telomere caps in pre-cancerous cells, then this causes genetic alterations that hasten the progression to cancer. Understanding mechanisms of telomere damage and repair should lead to new intervention strategies aimed at preserving these regions of the genome that are so critical for protecting our chromosomes and maintaining youthful cells. Conversely, we aim to leverage new findings to develop therapeutic strategies that deplete telomeres in cancer cells to prevent them from dividing.
Heath D. Skinner, MD, PhD, is a Professor in as well as the Chair of the Department of Radiation Oncology at the University of Pittsburgh and UPMC Hillman Cancer Center. In addition to his leadership and clinical duties, Dr. Skinner maintains an active, translational research laboratory focused upon identifying novel, clinically targetable biomarkers of resistance to radiation. His group utilizes "big data" approaches to clinical specimens as well as in vivo screening techniques to generate novel targets for study. These targets are then further investigated in vitro, to elicit insights regarding mechanisms of radioresistance. Dr. Skinner's research is designed to generate insights that led to the rational design of clinical trials using agents that are currently under investigation to minimize the time from bench to bedside. In addition to several current R01 grants, he is PI (along with Dr. Robert Ferris) of the UPMC Hillman Cancer Center Head and Neck SPORE.
Dr. St. Croix is a tenured Professor of Cell Biology and an Associate Director of the CBI. She has been a PI or co-I on NIH-funded R01s, P01s and R21s, and has been continuously funded by the NIH since 2005. A major focus of the St. Croix laboratory is the use of advanced optical imaging technologies to dissect molecular signaling pathways controlling vascular function in rodent and zebrafish model systems of disease. Within the CBI, Dr. St Croix manages and directs the use and application of fluorescence-based optical microscopy with an emphasis on advanced tools multiparametric live cell microscopy, focused light intravital small animal imaging, super-resolution microscopy methods and complex image processing.
Dr. Donna Beer Stolz is the Associate Director of the Center for Biologic Imaging, University of Pittsburgh School of Medicine, and Professor in the Departments of Cell Biology and Pathology at the University of Pittsburgh. She has been the director of the Electron Microscopy arm if the CBI since 1997. Prior to arriving at the university, Dr. Stolz received her BS in Biochemistry in 1986 and a PhD in Molecular and Cellular Biology in 1991 from the University of Massachusetts, Amherst.
Dr. Stolz is the author/coauthor of over 370 publications from her work at the Center for Biologic Imaging as well as from her own research efforts. Her primary interests lie in coordinating imaging studies with investigators using transmission and scanning electron microscopy approaches and integrating a wide variety of optical and electron imaging technologies in cell biology. She is actively involved in medical and graduate student teaching.
Some of Dr. Stolz’s cancer-related outreach activities include:
Our laboratory studies the formation and repair of DNA damage in nuclear and mitochondrial genomes. We are particularly interested in the structure and function of proteins that mediate DNA repair and the role of oxidative stress in human disease. We use state-of-the-art single molecule, biochemical and cell biology tools.
Dr. Wang’s primary areas of research interest include design and statistical analysis of clinical trials and pre-clinical studies, and correlated survival analysis. Other areas of interest include microbiome data analysis, statistical analysis of Multiplex Immunofluorescence (mIF) data, and in vitro and in vivo radiation survival analysis.
As a Research Associate Professor in the Department of Biostatistics, and Biostatistician and former Interim Director of UPMC Hillman Cancer Center (HCC) Biostatistics Facility, Dr. Wang has been collaborating with HCC medical investigators since 2004 by leading the statistical support of the Skin Cancer, Radiation Oncology, and Prostate/GU program. He has designed over 70 clinical trials. He has been working as a statistical reviewer for UPMC HCC PRC since 2006. He is the Co-Director of Biostatistics/Bioinformatics Core for Melanoma SPORE, and lead statistician for the NCI ETCTN trials Pittsburgh consortium. He has mentored 3 GSRs and advised 2 MS students.
Optical Microscopy has formed the core of my research career since my graduate training in England. In the CBI which I founded and direct, we build, test, and use cutting edge optical tools for all types of research microscopic imaging in cells, tissues and animals from the single molecule to the whole animal, the goal being to build highly flexible, maximally effective imaging solutions, to be used by academic researchers. In fact a major focus of my career and of the Center is to develop, train and imbue researchers at all levels (undergraduate, student, post-doc and faculty) with a solid understanding (both theoretical and practical) of the power of microscopy. As a professor of Cell Biology a major focus of my research has been to develop, build, and apply computer aided microscopes and analysis tools for imaging subcellular events at all levels of resolution within fixed and living systems. These include high speed Total internal Reflection Fluorescence microscopes able to image at 100 frames/second, high speed confocal systems able to collect multicolor 3D stacks in the second timeframe and other prototype confocal systems able to scan very large tissue sections with submicron resolution at very high speed. Most recently we have been developing very high speed deep tissue imaging solutions to collect quantitative images at the diffraction limit of entire tissues including brain, and building automated multi-spectral upright solutions combined with deep learning methods to dissect spectrally complex multiplex samples, including novel approaches for studying collagen organization in large tissue volumes.
