Investigators

Summary

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.

Summary

The main interest of Dr. Oesterreich's laboratory is to further our understanding of hormone action in women's cancers (including both breast and ovarian cancers), with the ultimate goal to use this knowledge for improved diagnosis and endocrine treatment. These studies include many aspects of translational breast cancer research utilizing basic biochemistry, molecular and cell biology, and cell lines, mouse models and clinical samples. Over the last few years, Dr. Oesterreich has developed a strong research interest in in situ and invasive lobular disease, the second most common yet understudied histological subtype of breast cancer. In her role as Director of Education at the Women's Cancer Research Center, Dr. Oesterreich is also very interested in providing outstanding training opportunities to the next generation of women's cancer researchers.

Summary

I am a clinical scientist in the department of Radiation Oncology whose academic career is focused on the rational use of radiation therapy in the context of multidisciplinary cancer therapeutics, specifically focusing on the role of radiation therapy with immunotherapy. I have active collaborations with Drs. Jason Luke and Riyue Bao in the TIIL lab to leverage complex datasets to identify optimal patients for whom radiation therapy might be most beneficial. I am committed to an investigative career at UPMC HCC and foresee an important role as a primary investigator in biomarker driven clinical trials as well as a collaborator with medical and surgical oncology to provide quality radiation oncology input and support for multimodality trials.

Summary

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. 

Summary

Research in the Orwig laboratory focuses on stem cells, germ lineage development, fertility, and infertility. Our progress investigating reproductive function in fertile individuals provides a basis for understanding the mechanisms of infertility caused by disease, medical treatments, genetic defects, or aging.  Infertility impacts one in seven couples in the United States and can have a devastating impact on relationships and emotional well-being.  The Orwig lab is ideally located in Magee-Womens Research Institute and Magee-Womens Hospital and is committed to translating lab bench discoveries to the clinic for diagnosis, prevention, and treatment of infertility. 

Summary

Our group's primary focus is on developing integrative machine learning approaches for extracting therapeutic and biological insights from highly heterogeneous omic datasets, clinical and drug response data, with the purpose of advancing precision medicine. Our projects span across the following areas: 

• Cancer Genomics: Leveraging machine learning techniques to analyze genomic data from cancer patients, identifying genetic mutations, biomarkers, and potential therapeutic targets for personalized cancer treatment.
• Single Cell and Spatial Omics: Developing statistical methods for single-cell multi-omics integration, integrating data from different omic layers (such as genomics, proteomics, transcriptomics, epigenomics) to gain a comprehensive understanding of cellular processes and disease mechanisms.
• Epigenetics: Studying how epigenetic modifications influence an individual's response to different drugs, integrating epigenetic data with clinical information to develop predictive models for personalized drug selection.

Our projects are executed through multi-disciplinary collaborations, recognizing that precision medicine requires expertise from various domains. By leveraging machine learning and integrating diverse datasets, our aim is to contribute to the advancement of precision medicine, ultimately leading to more targeted and effective treatments for patients.

Summary

My broad research program will address the following question: How can the microbiome-specific immune response be modified or targeted to improve cancer patient response to immunotherapy? I will utilize the expertise and tools I have developed throughout my training to track and modify tumor- and microbiota-specific T cells in hopes of identifying current immunotherapeutic hurdles and developing targeting strategies for these unique cell populations. In addition, I will assess how previous therapies or other external changes to the gut microbiome impact response to immunotherapy in both mouse models and patient samples. Ultimately, I will define the interplay between the immune responses to the ever-changing gut microbiome during tumorigenesis. These studies have the potential to not only improve our understanding of resistance to immunotherapy in cancer, but also to identify novel means of enhancing anti-tumor responses through modulation of the microbiota or its products.

My previous work as a Damon Runyon postdoctoral fellow in the Hand lab focused on the study of bacteria-specific CD4+ T cells in colorectal cancer (CRC) after microbiome modulation with a single bacteria, Helicobacter hepaticus (Hhep). We found that bacteria-specific CD4+ T cells were sufficient to drive anti-tumor immunity and lead to an increase in organized tertiary lymphoid structures and tumor immune infiltration. Interestingly, tumor clearance was dependent on CD4+ T cells but not CD8+ T cells, the latter of which is the primary target population for most immunotherapies. These observations were published in Immunity (2021) and suggested for the first time that CD4+ T cells that are specific to the microbiome directly support the anti-tumor immune response and may represent a new therapeutic target in tumors that occur at barrier surfaces such as CRC. In addition, I have recently found that modulation of the colon microbiome through colonization with Hhep can have beneficial impacts on tumors located in distant barrier sites as well, such as the skin. I have combined a number of innovative tools and techniques with tumor lines that contain controlled and tunable neoantigens to track tumor- and bacteria-specific immune responses. I believe that these models will provide tremendous and unique tools that will aid my overarching research program of study.