Guocan Wang
Assistant Professor
The University of Texas MD Anderson Cancer Center
Department of Genitourinary Medical Oncology-Research
My research interests focus on understanding how the genetic makeup of cancer and the heterogeneity in the tumor microenvironment (TME) influences cancer progression, metastasis, and therapy resistance at the molecular and cellular levels. Our long-term goal is to translate the basic findings in the laboratory into drug discovery and patient care.
We use a multi-disciplinary approach that includes unbiased computational analyses of multi-OMICS data (transcriptomics, epigenomics, proteomics, and metabolomics), genetically engineered mouse models (GEMMs), and cross-species and integrative analyses of human and mouse OMICS data. Importantly, we employ cutting-edge single-cell technologies in our research, including CyTOF, single-cell RNA-seq, single-cell ATAC-seq, and imaging mass cytometry.
Our current work largely focuses on three major areas:
(1) The role of myeloid-derived suppressor cells in cancer progression, metastasis, and therapeutic resistance. Previously, we demonstrated that targeting the Yap1- dependent infiltration of myeloid-derived suppressor cells (MDSCs) into tumors can be an effective therapeutic approach in advanced prostate cancer. Part of our ongoing work is to (a) investigate the role of MDSCs in the development of castration resistant prostate cancer, (b) elucidate the molecular mechanisms by which MDSCs suppress anti-tumor immunity, (c) identify novel therapeutic targets in MDSCs and develop inhibitors, and (d) identify effective combination therapy using MDSCs targeting agent and immune checkpoint inhibitors.
(2) The role of epigenetic regulators in driving cancer progression cells, metastasis, and therapeutic resistance, with a focus on histone lysine demethylases, histone lysine methyltransferases, and chromatin remodelers. We recently identified histone lysine demethylase KDM4A as an epigenetic driver of tumor progression in neuroendocrine prostate cancer (NEPC), one of the most lethal subtypes of advanced prostate cancer that lack effective therapy. We continue to study the functions of KDM4A in NEPC and examine the efficacy of KDM4A targeting agents as monotherapy and combination therapy.
(3) The role of immunometabolism dysregulation in cancer progression, metastasis, and therapeutic resistance. Immunometabolism refers to the intricate interplay between immune and metabolic pathways that plays a crucial role in health and disease, including cancer. Recent studies have shown that metabolic reprogramming, a hallmark of cancer, results in metabolic stress in T cells, leading to a cold immune tumor microenvironment (TME) that severely limits the efficacy of T cell–based immunotherapy. Thus, targeting dysregulated metabolic pathways has emerged as a promising therapeutic strategy in cancer, potentially enhancing the response of patients to immunotherapy, including patients with prostate cancer (PCa). We will focus on metabolic reprogramming in neuroendocrine prostate cancer (NEPC) and MDSCs.
Education & Training
PhD, Cornell University, 2011
MD, Sun Yat-Sen University, 2001