Research Interests:
Stem cell development Cancer stem cells Cancer cell heterogeneity Prostate cancer Non-coding RNAs and Epigenetics Experimental therapeuticsAbout Dean Tang
Biography:
Dean Tang, PhD, was trained as a Pathologist and is currently Professor & Chair in Department of Pharmacology & Therapeutics at Roswell Park Comprehensive Cancer Center. I am also the Co-Leader of the CCSG Developmental Therapeutics (DT) Program and Chair of the Experimental Therapeutics (ET) Graduate Program. I also hold the George Decker Endowed Chair in Developmental Therapeutics. My Master of Science research (1986-1989), conducted in Dr. Hong-Shen Tian’s laboratory in Wuhan University School of Medicine (China), focused on establishing lung cancer metastasis models. To continue my research on cancer metastasis, I pursued my PhD Thesis Research in Dr. Kenneth V. 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. I obtained my PhD in Cancer Biology in May of 1994.
In 1998, I 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). I returned to the U.S 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 I was recruited to Roswell Park as the Chair of Department of Pharmacology & Therapeutics.
For the past 20 years (since 2002), my colleagues and I have been applying the knowledge of normal stem cell biology to elucidate the fundamental biological principles that govern the generation of tumor cell heterogeneity via cancer stem cells (CSCs) and of cancer cell plasticity via epigenetic mechanisms. By focusing on prostate cancer (PCa), the lab has characterized the biological and tumorigenic properties and identified novel molecular regulators of prostate CSCs (PCSCs). Our recent work on PCa cell AR heterogeneity has been translated into a phase I/IIb clinical trial (NCT03751436; Chatta, PI) that treats mCRPC patients with a combination of enzalutamide and the FDA-approved BCL-2 specific inhibitor Venetoclax.
Positions
Roswell Park Comprehensive Cancer Center
- Professor of Oncology
- George Decker Endowed Chair in Developmental Therapeutics
- Chair, Department of Pharmacology & Therapeutics
- Co-Leader, CCSG Developmental Therapeutics Program
- Director, Experimental Therapeutics PhD Track
Background
Education and Training:
- 1994 - PhD - Cancer Biology - Wayne State University Medical School, Detroit, MI
- 1986-1989 - MS - Cancer Biology - Wuhan University School of Medicine, Wuhan, China
Residency:
- Oncological Pathology - Wuhan, China
Fellowship:
- 1998-2000 – Postdoctoral Fellow – MRC Laboratory for Molecular Cell Biology, London
Professional Experience:
- 2016 - present - Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY
- 2000-2016 - Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D Anderson Cancer Center, Houston, TX
Honors & Awards:
- 2021 - George Decker Endowed Chair in Developmental Therapeutics, Roswell Park Comprehensive Cancer Center
- 2021 - Co-organizer, the Keystone eSymposia, ‘Stem Cells and Cancer’
- 2016 - Fellow of AAAS (American Association of Advancement of Science)
- 2014 - The Spandidos Publications Award for Outstanding Scientific Achievement
- 2013 - Keynote Speaker, “Cancer Stem Cells: The Mechanisms of Radioresistance and Biomarker Discover Symposium,” Dresden, Germany
- 2012 - Sanofi - Cell Research Outstanding Review Paper Award
- 2007 - The Robert M. Chamberlain Distinguished Mentor Award, The University of Texas M.D. Anderson Cancer Center
- 2003-2007 - American Cancer Society (ACS) Research Scholar
- 1998-2002 - Burroughs Wellcome Fund Hitchings-Elion Award
Research
Research Overview:
Our lab research aims to elucidate the fundamental biological principles that govern the generation of tumor cell heterogeneity via cancer stem cells (CSCs) and cancer cell plasticity via 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 and tumorigenic properties and identified novel molecular regulators of prostate cancer stem cells (PCSCs). We have recently shown that PCa cell heterogeneity, especially heterogeneity in AR expression, has a great impact on PCa cell response to clinical therapies. This line of research has been translated to a phase I/IIb clinical trial (NCT03751436; Chatta, PI) 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.
1. Investigate normal prostate epithelial cell heterogeneity & hierarchy and PCa cell(s)-of-origin
2. Elucidate PCa cell heterogeneity and plasticity: Roles in therapy resistance, relapse & metastasis
3. Uncover molecular regulators and therapeutic targets of PCSCs and CRPC
4. Dissect PCa cell heterogeneity and immunity & PCa cell coevolution with the TME
5. Develop novel therapeutics and therapeutic combinations to tackle PCa heterogeneity and plasticity
Pharmacology and Therapeutics Lab Members:
- Rahul Kumar
- Jason Kirk
- Amanda Tracz
- Wen (Jess) Li
- Anmbreen Jamroze
- Xiaozhuo(Dalton) Liu
- Ruifang(Nancy) Liu
- Moyi Wang
- Shan Wu
- Emily Dougherty
Publications
Representative Publications:
- Dingxiao Zhang, Qiang Hu, Xiaozhuo Liu, Yibing Ji, Hsueh-Ping Chao, Yan Liu, Amanda Tracz, Jason Kirk, Silvia Buonamici, Ping Zhu, Jianmin Wang, Song Liu, Dean G. Tang. Intron retention is a hallmark and spliceosome represents a therapeutic vulnerability in aggressive prostate cancer. Nat Commun 11, 2089 (2020). PMID: 32350277
- Li Q, Liu B, Chao HP, Ji Y, Lu Y, Mehmood R, Jeter C, Chen T, Moore JR, Li W, Liu C, Rycaj K, Tracz A, Kirk J, Calhoun-Davis T, Xiong J, Deng Q, Huang J, Foster BA, Gokhale A, Chen X, Tang DG. LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer. Nat Commun. 2019 Dec 2;10(1):5494. doi: 10.1038/s41467-019-13532-4. PMID: 31792211; PMCID: PMC6889295.
- Li Q, Deng Q, Chao HP, Liu X, Lu Y, Lin K, Liu B, Tang GW, Zhang D, Tracz A, Jeter C, Rycaj K, Calhoun-Davis T, Huang J, Rubin MA, Beltran H, Shen J, Chatta G, Puzanov I, Mohler JL, Wang J, Zhao R, Kirk J, Chen X, Tang DG. Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nat Commun. 2018 Sep 6;9(1):3600. doi: 10.1038/s41467-018-06067-7. PMID: 30190514; PMCID: 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. 2018 Jan 9;10(1):228-242. doi: 10.1016/j.stemcr.2017.11.016. Epub 2017 Dec 21. PMID: 29276153; PMCID: PMC5768933.
- Liu C, Liu R, Zhang D, Deng Q, Liu B, Chao HP, 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. Nat Commun. 2017 Jan 23;8:14270. doi: 10.1038/ncomms14270. PMID: 28112170; PMCID: 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. Clin Cancer Res. 2016 Sep 1;22(17):4505-16. doi: 10.1158/1078-0432.CCR-15-2956. Epub 2016 Apr 8. PMID: 27060154; PMCID: 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. 2016 Feb 29;7:10798. doi: 10.1038/ncomms10798. PMID: 26924072; PMCID: 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, Tang DG. The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell. 2012 May 4;10(5):556-69. doi: 10.1016/j.stem.2012.03.009. PMID: 22560078; PMCID: 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, Tang DG. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011 Feb;17(2):211-5. doi: 10.1038/nm.2284. Epub 2011 Jan 16. PMID: 21240262; PMCID: PMC3076220.
- Laffin B, Tang DG. An Old Player on a New Playground: Bmi-1 as a Regulator of Prostate Stem Cells. Cell Stem Cell. 2010 Dec 3;7(6):639-40. doi: 10.1016/j.stem.2010.11.019. PMID:21112554.
- Chandra D, Bratton SB, Person MD, Tian Y, Martin AG, Ayres M, Fearnhead HO, Gandhi V, Tang DG. Intracellular nucleotides act as critical prosurvival factors by binding to cytochrome C and inhibiting apoptosome. Cell. 2006 Jun 30;125(7):1333-46. doi: 10.1016/j.cell.2006.05.026. PMID: 16814719.
- Tang DG, Tokumoto YM, Apperly JA, Lloyd AC, Raff MC. Lack of replicative senescence in cultured rat oligodendrocyte precursor cells. Science. 2001 Feb 2;291(5505):868-71. doi: 10.1126/science.1056780. Epub 2001 Jan 18. PMID: 11157165.