Dean Tang, PhD, was trained as a Pathologist and is currently Professor & Chair in Department of Pharmacology & Therapeutics at Roswell Park Comprehensive Cancer Center. He also acts as a Co-Leader of the CCSG Developmental Therapeutics (DT) Program and Director of the Experimental Therapeutics (ET) Graduate Program. Dean’s Master of Science research (1986-1989), conducted in Dr. Hong-Shen Tian’s laboratory in Wuhan University School of Medicine, focused on establishing lung cancer metastasis models. To continue his research on cancer metastasis, Dean joined Dr. Ken Honn’s lab at Wayne State University (WSU, Detroit, MI, USA) in 1989 to study the roles of integrin receptors and eicosanoids in mediating and regulating tumor cell-extracellular matrix interactions, and tumor cell invasion and dissemination. He obtained his PhD in Cancer Biology in 1994.
In 1998, Dean was awarded a Burroughs-Wellcome Hitchings-Elion post-doctoral fellowship to study oligodendrocyte precursor cell (OPC) development in Dr. Martin Raff’s lab in Medical Research Council (MRC) Laboratory for Molecular & Cellular Biology (LMCB) of University College London (UCL, UK). Dr. Tang returned to the States in June of 2000 to join as a faculty in Department of Epigenetics and Molecular Carcinogenesis at the University of Texas M.D Anderson Cancer Center (MDACC) till end of May in 2016, when he moved to Roswell Park.
Since 2002, Dean and his colleagues have been applying normal stem cell biology knowledge to elucidate the fundamental biological principles that govern the generation of tumor cell heterogeneity via cancer stem cells (CSCs) and epigenetic mechanisms. By focusing on prostate cancer (PCa), the lab has characterized the biological, molecular, and tumorigenic properties of prostate CSCs (PCSCs). Their recent work has shown that PCa cell heterogeneity, especially heterogeneity in AR expression and status, has a great impact on PCa cell responses to clinical therapies. One line of the lab research has been translated into a phase I/IIb clinical trial (NCT03751436) that treats mCRPC patients with a combination of enzalutamide and the only FDA-approved BCL-2 specific inhibitor Venetoclax.
Our lab research aims to elucidate the fundamental biological principles that govern the generation of tumor cell heterogeneity via cancer stem cells (CSCs) and epigenetic mechanisms, and to take our newly gained knowledge to translate to the clinic. By focusing on prostate cancer (PCa), we have characterized the biological, molecular, and tumorigenic properties, of prostate CSCs (PCSCs). We have recently shown that PCa cell heterogeneity, especially heterogeneity in AR expression, has a great impact on PCa cell responses to clinical therapies. One line of our research has been translated into a phase I/IIb clinical trial (NCT03751436) that treats mCRPC patients with a combination of enzalutamide and the only FDA-approved BCL-2 specific inhibitor venetoclax. The lab has several inter-connected research projects encompassing: 1) elucidating normal prostate cell heterogeneity and hierarchy and investigating cell-of-origin of PCa subtypes; 2) dissecting PCa cell heterogeneity and plasticity and linking them to therapy response and tumor recurrence; 3) uncovering novel molecular regulators of PCSCs; and 4) developing novel therapeutics and therapeutic combinations to tackle PCa cell heterogeneity and plasticity.
Listed below are several representative publications. For a complete list of publications, please visit: https://www.ncbi.nlm.nih.gov/pubmed/?term=tang+dg
Li Q, Deng Q, Chao H, Liu X, Lu Y, Lin K, Liu B, Tang G, Zhang D, Tracz A, Jeter C, Rycaj K, Calhoun-Davis T, Huang J, Rubin M, Beltran H, Shen J, Chatta G, Puzanov I, Mohler J, Wang J, Zhao R, Kirk J, Chen X, Tang DG. Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nat. Commun. 9(1):3600. 2018. PMCID: PMC6127155; https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC6127155
Zhang D, Jeter C, Gong S, Tracz A, Lu Y, Shen J, Tang DG. Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration. Stem Cell Reports 10(1):228-42. 2018. PMCID: PMC5768933; https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC5768933
Liu C, Liu R, Deng Q, Liu B, Chao H.P., Rycaj K, Takata Y, Lin K, Lu Y, Zhong Y, Krolewski J, Shen J, Tang, DG. MicroRNA-141 Suppresses Prostate Cancer Stem Cells and Metastasis by Targeting a Cohort of Pro-Metastasis Genes Including CD44, Rho GTPases, and EZH2. Nat Commun. 8:14270, 2017. PMCID: PMC5264244; https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC5264244
Chen X, Li Q, Liu X, Liu C, Liu R, Rycaj K, Zhang D, Liu B, Jeter C, Calhoun-Davis T, Lin K, Lu Y, Chao HP, Shen J, Tang DG. Defining a population of stem-like human prostate cancer cells that can generate and propagate castration-resistant prostate cancer (CRPC). Clin Cancer Res. 22:4505-4516, 2016. PMCID: PMC5010458; https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC5010458
Zhang D, Park D, Zhong Y, Lu Y, Rycaj K, Gong S, Chen X, Liu X, Chao HP, Whitney P, Calhoun-Davis T, Takata Y, Shen J, Iyer VR, Tang DG. Stem cell and neurogenic gene expression profiles link prostate basal cells to aggressive prostate cancer. Nat Commun 7:10798, 2016. PMCID: PMC4773505; https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC4773505
Qin J, Liu X, Laffin B, Chen X, Choy G, Jeter CR, Calhoun-Davis T, Li H, Palapattu GS, Pang S, Lin K, Huang J, Ivanov I, Li W, Suraneni MV, and Tang DG. The PSA-/lo prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 10: 556-569, 2012. PMCID: PMC3348510; https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC3348510
Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, and Tang DG. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nature Med. 17: 211-215, 2011. PMCID: PMC3076220; https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC3076220
Laffin B, Tang DG. An old player on a new playground: Bmi-1 as a regulator of prostate stem cells. Cell Stem Cell 7: 639-40, 2010. PMID: 21112554; https://www.ncbi.nlm.nih.gov/pubmed/?term=21112554
Chandra D, Bratton SB, Person MD, Tian Y, Martin AG, Ayers M, Fearnhead HO, Gandhi V, and Tang DG. Intracellular nucleotides act as critical prosurvival factors by binding to cytochrome c and inhibiting apoptosome. Cell 125: 1333-1346, 2006. PMID: 16814719; https://www.ncbi.nlm.nih.gov/pubmed/?term=16814719
Tang DG, Tokumoto YM, Apperly JA, Lloyd AC, Raff MC. Lack of replicative senescence in cultured rat oligodendrocyte precursor cells. Science 291:868-871, 2001. PMID: 11157165; https://www.ncbi.nlm.nih.gov/pubmed/?term=11157165