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An NCI-designated Comprehensive Cancer Center, affiliated with the University of Pittsburgh School of Medicine
Research
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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.
The goals of my research program include: (1) define the cellular and molecular mechanisms of immune evasion during cancer development; (2) develop more effective cancer immunotherapy, with a focus on head and neck squamous cell carcinomas (HNSCCs) and B cell lymphomas; (3) elucidate the basic mechanisms of antibody gene diversification and B cell lymphomagenesis. We employ mouse models, human samples, and novel methodologies to elucidate mechanisms underlying the heterogeneous responses to immune checkpoint inhibitors in HNSCCs.
The Cancer Genome Project Initiatives have generated a daunting amount of genomic and deep sequencing data for tens of thousands of human tumors. An overarching challenge of this post-genomic era is to identify and recognize the cancer drivers and targets from these big genomic data, especially those that can be therapeutically targeted to improve the clinical outcome. The mission of our lab is to apply a multiple disciplinary approach inclusive of integrative bioinformatics, cancer genetics, molecular cancer biology, and translational studies to identify driving genetic aberrations and appropriate cancer targets on the basis of deep sequencing and genomic profiling datasets. Our research projects are composed of both computational and laboratory components. Our dry lab researches focus on developing innovative and integrative computational technologies to discover causal genetic and epigenetic alternations, viable therapeutic targets, and predictive biomarkers in cancer. In particular, we have innovated a concept signature (ConSig) analysis that employs molecular fingerprints for high-throughput interpretation of the biological function of candidate targets in cancer (Nature biotech 2009). In addition, we have formulated a 'fusion breakpoint principle' that describes the intragenic copy number aberrations characteristic of recurrent gene fusions, thus enabling genome-wide detection of copy number breakpoints generating gene fusions. Based on these principles we further developed a powerful bioinformatics tool called 'Fusion Zoom' that identifies recurrent pathological gene fusions via integrative analyses of RNA sequencing, copy number, and gene concept datasets (Nature Commun 2014). Further, we have discovered the crucial application of ConSig analysis in revealing the primary oncogenes targeted by genomic amplifications, and developed a new integrative genomic analysis called 'ConSig-Amp' to detect viable cancer targets. Moreover we also developed an integrated computational-experimental approach called HEPA-PARSE for the genome-wide detection of clinically important tumor specific antigen (TSA) targets (Cancer Research 2012). Our wet lab researches focus on experimentally characterizing individual genetic and epigenetic aberrations in breast cancer such as recurrent gene fusions, genomic amplifications, and epimutations, as well as qualifying viable cancer targets and predictive biomarkers for the development of precision therapeutics in breast cancer. Our current disease focus is clinically intractable breast cancers, such as luminal B or basal-like tumors. In particular, by applying the FusionZoom analysis to the RNAseq and copy number data from The Cancer Genome Atlas, we have discovered a novel recurrent gene fusion involving the estrogen receptor gene in a subset of breast cancers. This fusion called ESR1-CCDC170 is preferentially present in 6-8% of luminal B tumors -- a more aggressive subtype of estrogen receptor positive breast cancer. To date, this is the first and most frequent gene fusion yet reported in this tumor entity (Nature Commun. 2014). We are now assessing the druggability of this fusion with the goal of developing effective targeted therapy against this genomic target. We expect that our new discoveries will yield novel insights into the recurring genetic abnormalities leading to breast cancer initiation, progression, and therapeutic resistance, and establish viable targets for effective intervention.
My research focuses on clinical natural language processing, digital phenotyping, clinical data infrastructure, cohort identification for clinical and translational research. My primary focus lies in leveraging electronic health records (EHRs), with a particular emphasis on unstructured EHR data, including, but not limited to, clinical notes, radiology reports, and pathology reports. I have expertise in developing natural language processing (NLP) algorithms to extract valuable information from these sources, such as cancer stage, histology, tumor grade, cancer subtypes, and treatment outcomes. Furthermore, I've designed cohort exploration tools to facilitate feasibility studies for clinical trials and streamline patient recruitment by harnessing the power of EHRs.
I am doing cancer research related to molecular biology, genetics, data mining with bioinformatics and immunology. According to immune relationship with cancers, there are hot tumors and cold tumors including immune cells exclusion and immune cell deserts to influence the progress of cancer patients, the "hot" tumors with immune infiltration has more chance for the carriers to get complete response to ICI therapy and chemotherapy. Our T cell migration test followed by flowcytometry showed the TNBC (Triple negative breast cancer) which has gene fusions of BCL2L14ETV6 has more resistant to T cells migration (especially CD8) through different cytokine/chemokine "talk" with T cells. The preliminary data also shows BCL2L14-ETV6 fusions orchestrate immunosuppressive and protumor cytokines contexture and impair immune cell infiltration. In addition, it modulates the target genes of NFkb, a central mediator of inflammation, endows epithelial mesenchymal transition, confers paclitaxel resistance.
In addition, Low-cost multi-omics sequencing is expected to become clinical routine and transform precision oncology. Viable computational methods that can facilitate tailored intervention while tolerating sequencing biases are in high demand. Here we propose a class of transparent and interpretable computational methods called integral genomic signature (iGenSig) analyses, that address the challenges of cross-dataset modeling through leveraging information redundancies within high-dimensional genomic features, averaging feature weights to prevent overweighing, and extracting unbiased genomic information from large tumor cohorts.we develop a battery of iGenSig models for predicting cancer drug responses, and validate the models using independent cell-line and clinical datasets. The iGenSig models for five drugs demonstrate predictive values in six clinical studies, among which the Erlotinib and 5-FU models significantly predict therapeutic responses in three studies, offering clinically relevant insights into their inverse predictive signature pathways. Together, iGenSig provides a computational framework to facilitate tailored cancer therapy based on multi-omics data. (Nature Communication 2022)
In addition, I am culturing different kinds of T cells and look into potential T cell therapies for cancers in the future. I did T cell repertoire analysis on PBMC from pancreatic cancer patients, which showed the more versatile of T cell repertoire system the better potential response rate from chemotherapy and other therapies. Also, I got some certifications from Lifestyle Medicine which includes 6 pillars of nutrition science, exercise physiology, sleep science, stress management, positive psychology, removal dictation, which can demonstrate to have the potential to reverse some chronic diseases.
One focus of my lab is to investigate the mechanisms regulating androgen receptor (AR) nuclear localization, particularly androgen-independent AR nuclear localization in castration-resistant prostate cancer (CRPC) which is the second leading cause of cancer death in American men. AR remains to be the key driver in majority of CRPC tumors resistant to the current AR targeting agents. AR nuclear localization is necessary for its function as a transcription factor. According to the classical model of AR nucleocytoplasmic trafficking, AR is present in the cytoplasm in the absence of androgens, which can be imported into the nucleus in the presence of androgens, and the imported AR will be exported upon androgen withdrawal. However, this model is not supported by our recent discovery that imported nuclear AR is degraded, but not exported, upon androgen withdrawal and that unliganded AR can be also imported and rapidly degraded in the nucleus. These findings promoted us to investigate the mechanism of nuclear-specific AR degradation. Identification and characterization of factors responsible for nuclear-specific AR degradation will allow us to investigate if and how these factors are dysregulated in CRPC cells. In addition, we will continue developing novel AR antagonists, with collaborations with experts in medicinal chemistry and structural biology, to identify and characterize small molecules that can inhibit androgen-independent AR nuclear localization in CRPC.
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.
In addition to specializing in pediatric and adult orthopaedic oncology, Dr. Weiss directs a basic science laboratory dedicated to the study of sarcomas ' cancerous tumors that arise in musculoskeletal tissues. As a bone cancer survivor himself, Dr. Weiss brings passion and enthusiasm to the laboratory, clinic, and operating room.
The Wells Laboratory research program, in close collaboration with its research partners, aims to understand cell migration in terms of how motility processes are regulated, and understand how this regulation of migration plays a role in physiologic and pathologic situations. We are integrating the knowledge gained from our biochemical and biophysical mechanistic studies into our investigations concerning conditions of dysregulated (tumor invasion) and orchestrated (wound healing and organogenesis) cell motility. As part of understanding the motility response, we are investigating both how this particular integrated cell response is selected from among others and the metabolic consequences of motility. This integrative approach provides reinforcing insights and novel avenues for exploration into the basic signaling pathways as well as functioning of whole organism. As a model system, we explore motility signaling from the epidermal growth factor receptor (EGFR) in adherent cells. EGFR plays a central role in the functioning in a wide variety of both stromal and epithelial tissues, and is the prototype for other receptors with intrinsic tyrosine kinase activity. Thus, these studies should have widespread implications.
The two central foci are tumor progression and wound repair. In tumor progression, we examine breast and prostate carcinoma invasion and metastases in terms of molecular signals and the special micro-environments. For this, the laboratory uses human tissues, animal models, and a unique 4-dimensional liver microtissue. In would repair, the current model system is skin wound healing, in which the communications between the epidermis, dermis, and blood vessels is parsed at the molecular levels. The role of stem cells in the natural repair process and as a rationale therapeutic is also being investigated. These two areas are re-inforcing as many of the key molecules and cellular processes are part of the generalizable onco-fetal-wound program.
The focus of my research is the genetics of postoperative symptoms. Specifically, I am studying the association of several genes and postoperative and post-discharge nausea and vomiting in women following surgery for breast and ovarian cancer. We would like to be able to understand why some women do not respond to antiemetic medications, and to predict who is at greatest risk.
Dr. Whiteside’s research interests are in tumor Immunology and immunotherapy with special focus on mechanisms of tumor-induced immunosuppression, extracellular vesicles, cytokine networks, immunology of human head and neck cancer, melanoma, acute myelogenous leukemia and breast cancer. Her research is focused on mechanisms of tumor escape from the host immune system and the development of therapies designed to eliminate tumor escape. She studies the role of check point inhibitors in cancer progression. Currently she is investigating contributions tumor derived small extracellular vesicles or exosomes (TEX) to promotion of cancer progression. Specifically, mechanisms of TEX-induced apoptosis of CD8+ effector T cells and activation of regulatory T cells are investigated. Also, studies are evaluating the potential of TEX in the body fluids of cancer patients to serve as “liquid cancer biopsy” in predicting cancer progression, response to therapy and survival. Studies of TEX as well as subsets of EVs produced by immune cells in re-programming of the tumor microenvironment are performed using human specimens and mouse models of tumor growth.
Despite high prevalence and mortality rates, few research programs focus on breast cancer liver metastasis and little is known about the impact of metastatic breast cancer cells on the liver microenvironment. My research program will fill these gaps in knowledge by testing the impact of breast cancer cell secreted factors on the liver metastatic microenvironment with the overall goal of identifying targetable pathways to enhance immune cell presence and activation at this deadly metastatic site.
Current research in my lab builds on my postdoctoral fellowship at the University of Colorado where I demonstrated that metabolites of tumor cell heme degradation are immune modulatory in breast cancer lung and lymph node metastasis. These projects are supported by an NIH/NCI-R00 that tests the impact of tumor cell heme metabolism on recruited and tissue resident immune cells in the metastatic liver. This work will also follow-up on preliminary evidence that suggests heme metabolism may support a global metabolic re-programming in metastatic breast cancer cells that allows survival in the metabolically active liver microenvironment. These studies will serve as a launchpad for my independent program that will continue to assess the effects of breast tumor cell signaling on the metastatic microenvironment.
Hillman Cancer Center (HCC) provides an exceptional environment for the development of my research program. I plan to take advantage of the expertise of HCC researchers in fields such as immunometabolism, tumor metabolism, breast cancer biology and treatment, and tumor immunology. Since my research bridges the focus of several HCC programs, I will accomplish this goal by participating in events hosted by and building collaborations with scientists from multiple programs such as the Cancer Biology, Cancer Immunology and Immunotherapeutic, Genome Stability, and Cancer Therapeutics Programs. I also hope to develop strong working relationships with clinical breast cancer researchers, such as Drs. Julia Foldi and Adam Brufsky, and members of the Immunotherapy and Drug Development Center that can provide insight and assistance as promising laboratory findings are developed for translation to the clinic. The outstanding HCC Shared Resources, including the Animal Facility, Biostatistics Facility, Cytometry Facility, Translational Pathology Imaging Laboratory, and Translational Oncologic Pathology Services will be instrumental as I address my research aims.
Dr. Wilson's research interests include: lung cancer screening and early detection, biomarker development and implementation, chemoprevention, diagnosis, staging and treatment of lung cancer; COPD, especially as it relates to lung cancer; occupational lung diseases; and general pulmonary medicine.
The Wipf group develops tools of synthetic organic chemistry in the search for innovative new therapies and therapeutics. We identify original synthetic methods, strategies and molecular mechanisms, and we apply them in medicinal chemistry and chemical biology, total synthesis, and natural products chemistry. We select target molecules on the basis of their unique architectures and biological activities, as well as for showcasing our synthetic methods. We employ insights from flow and photochemistry, material science and nanoparticle research to improve synthetic access and modify the properties of our target compounds. Most significantly, we are committed to collaborative drug discovery and development in diverse therapeutic areas, including oncology, neurodegeneration, fibrosis, neuromuscular diseases, inflammation, and immunology.
Norman Wolmark, MD, has spent decades conducting groundbreaking research and early clinical trials in the treatment of breast and bowel cancers. Many of his early studies were conducted at the University of Pittsburgh alongside the late Dr. Bernard Fisher. Dr. Wolmark serves as Chairman of the NSABP Foundation and as Group Chair and Contact Principal Investigator of the NCI-funded NRG Oncology research organization, which combined the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG). Dr. Wolmark is a member of a number of professional associations and organizations, including the American Society of Clinical Oncology, the American Association of Cancer Research, and the American Surgical Association. He has authored more than 400 scientific publications and has served on the editorial boards of publications such as the Journal of Clinical Oncology, the Journal of Surgical Oncology, and Clinical Breast Cancer, as well as having served as a reviewer for journals such as the Annals of Internal Medicine, Breast Cancer Research and Treatment, Cancer Research, and the New England Journal of Medicine. Dr. Wolmark lectures internationally and has been recognized for his invaluable contributions to practice-changing research.
I am a medical oncologist specializing in genitourinary cancers. My research interests are in symptom management and quality of life for patients with genitourinary cancers, particularly for patients with prostate cancer undergoing androgen deprivation therapy.
My research interfaces a broad range of interdisciplinary in computational science and medicine for translational and clinical applications. My main research areas include computational biomedical imaging analysis, big (health) data coupled with machine/deep learning, imaging-based clinical studies, radiomics/radiogenomics, and artificial intelligence in clinical informatics/workflows. Current research interests center on computational breast imaging and clinical studies for investigating quantitative imaging-derived biomarkers, models, and systems for breast cancer screening, risk assessment, diagnosis, prognosis, and treatment, towards improving individualized clinical decision-making and precision medicine. My research also covers other diseases/organs, such as pancreatic cancer, liver cancer, gastric cancer, traumatic brain injury, cardiac arrest, intestinalis, orthopedics, obesity, organoid, etc.
My lab received the prestigious "RSNA (Radiological Society of North America) Trainee Research Award" twice in 2017 and 2019, and the Natus Resident/Fellow Award for Traumatic Brain Injury by 2021 AANS (American Association of Neurological Surgeons). My lab's research is supported by NIH/NCI/NIBIB, NSF, RSNA, UPMC Enterprise, Pittsburgh Health Data Alliance, Pittsburgh Foundation, Stanley Marks Research Foundation, Amazon AWS, Nvidia, and many internal funding sources. I have published over 150 journal papers and conference papers/abstracts in both the computing and clinical fields, including in Nature Cancer, Nature Communications, Radiology, Clinical Cancer Research, Breast Cancer Research, Surgery, Resuscitation, IEEE Journal of Biomedical and Health Informatics, Pattern Recognition, AI in Medicine, IEEE Transactions on Cybernetics, CVPR, MICCAI, ICCV, IJCAI, ICRA, etc. My research has been featured in hundreds of scientific news reports and media outlets in the world. I founded and currently lead the Pittsburgh Center for AI Innovation in Medical Imaging (CAIIMI).
