University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Thea D. Tlsty, PhD

Thea D. Tlsty, PhD

Professor, Department of Pathology and Director of the Center for Translational Research in the Molecular Genetics of Cancer, UCSF; Director for the Program in Cell Cycling and Signaling, UCSF Helen Diller Family Comprehensive Cancer Center

Cancer Center Program Memberships

Breast Oncology

Research Summary

Dr. Tlsty has over 25 years of experience in studying human cells and the earliest responses to injury. She has lead multi-disciplinary groups that address both the epithelial and stromal contributions to wound healing and malignancy. The model systems the Tlsty laboratory has developed and the applied translational insights obtained have great potential to contribute to clinical utility.

Our work was the first to develop biomarkers for risk stratification of ductal carcinoma in situ, a pre-malignant lesion of breast cancer. Our recent work has identified molecular aspects of stromal-epithelial stress responses and the interactions that facilitate tumor progression in breast, prostate and other cancers. These analyses have enabled us to identify cell-extrinsic consequences of epithelial stress that lead to the activation of pro-tumorigenic stromal phenotypes. One of the most profound phenotypes involves the activation of a multicellular stromal program shared by high mammographic density and desmoplastic tumor tissues, characterized by repression of CD36. While studying these interactions we unexpectedly found a rare population of cells within disease-free tissue that has the potential to attain pluripotency. These cells have the ability to create functional tissues of all three germ layers which we hypothesize may be involved in metaplasia and inflammatory diseases. A single pluripotent cell can generate beating cardiomyocytes, lactating breast, bone, cartilage, vasculature, adipocytes, pancreas, and intestinal cells. We hypothesize that these cells may be the cell-of-origin for metaplastic cancers and provide insights for the identification of novel therapeutic targets. Similarly, these cells may be responsible for a wide collection of phenotypes that are initiated by chronic stress and defective in a wide spectrum of cancers. Our current studies, couched in a large multi-disciplinary, multi-investigator grant, are aimed at investigating the role of chronic inflammation in increased cancer incidence with the intent of developing preventive and therapeutic solutions.

Education

University of South Florida, Tampa, FL, B.S., 1973, Zoology
Washington University, St. Louis, MO, Ph.D., 1980, Molecular Biology
Washington University, St. Louis, MO, 1976-1980, Predoctoral Fellow
Stanford University, Stanford, CA, 1981-1984, Postdoctoral Fellow
Stanford University, Stanford, CA, 1984-1985, Senior Research Associate


Professional Experience

  • 1974-1976
    Ph.D. Candidate, Dept. of Pathology, University of North Carolina, Chapel Hill (transferred)
  • 1976-1980
    Pre-doctoral Fellow in Program for Cellular & Molecular Biology, Washington University, St. Louis, Missouri (advisor, Dr. M. Lieberman)
  • 1980-1981
    Postdoctoral Fellow in Dept. of Microbiology & Immunology, Washington Univ., St. Louis, MO
  • 1981-1985
    Postdoctoral Fellow/Senior Research Associate in Department of Biological Sciences, Stanford University, Stanford, California (advisor, Dr. R.T. Schimke)
  • 1985-1994
    Assistant/Associate Professor of Pathology and Member: UNC Lineberger Comprehensive Cancer Center; University of North Carolina at Chapel Hill, North Carolina
  • 1994-Present
    Professor of Pathology, Director of the Center for Translational Research in the Molecular Genetics of Cancer, Member: UCSF Comprehensive Cancer Center – Director for the Program in Cell Cycling and Signaling; Program in Biological Sciences (PIBS); Program in Biomedical Sciences (BMS), University of California at San Francisco, CA

Selected Publications

  1. Tlsty TD, Gascard P. Stromal directives can control cancer. Science. 2019 07 12; 365(6449):122-123.
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  2. Blagoev KB, Ting DT, Levine H, Saenger Y, Tlsty TD, Sun B. Introducing cancer convergence. Cancer Converg. 2017; 1(1):3.
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  3. Fuhrmann A, Banisadr A, Beri P, Tlsty TD, Engler AJ. Metastatic State of Cancer Cells May Be Indicated by Adhesion Strength. Biophys J. 2017 Feb 28; 112(4):736-745.
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  4. Pan D, Roy S, Gascard P, Zhao J, Chen-Tanyolac C, Tlsty TD. SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic cells requires CD73. Cell Signal. 2016 12; 28(12):1923-1932.
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  5. Molinaro AM, Sison JD, Ljung BM, Tlsty TD, Kerlikowske K. Risk prediction for local versus regional/metastatic tumors after initial ductal carcinoma in situ diagnosis treated by lumpectomy. Breast Cancer Res Treat. 2016 06; 157(2):351-361.
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  6. Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev. 2016 05 01; 30(9):1002-19.
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  7. Kurup A, Ravindranath S, Tran T, Keating M, Gascard P, Valdevit L, Tlsty TD, Botvinick EL. Novel insights from 3D models: the pivotal role of physical symmetry in epithelial organization. Sci Rep. 2015 Oct 16; 5:15153.
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  8. Drake CR, Estévez-Salmerón L, Gascard P, Shen Y, Tlsty TD, Jones EF. Towards aspirin-inspired self-immolating molecules which target the cyclooxygenases. Org Biomol Chem. 2015 Dec 07; 13(45):11078-86.
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  9. Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu YC, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh KH, Feizi S, Karlic R, Kim AR, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Neph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJ, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai LH, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M. Integrative analysis of 111 reference human epigenomes. Nature. 2015 Feb 19; 518(7539):317-30.
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  10. Gascard P, Bilenky M, Sigaroudinia M, Zhao J, Li L, Carles A, Delaney A, Tam A, Kamoh B, Cho S, Griffith M, Chu A, Robertson G, Cheung D, Li I, Heravi-Moussavi A, Moksa M, Mingay M, Hussainkhel A, Davis B, Nagarajan RP, Hong C, Echipare L, O'Geen H, Hangauer MJ, Cheng JB, Neel D, Hu D, McManus MT, Moore R, Mungall A, Ma Y, Plettner P, Ziv E, Wang T, Farnham PJ, Jones SJ, Marra MA, Tlsty TD, Costello JF, Hirst M. Epigenetic and transcriptional determinants of the human breast. Nat Commun. 2015 Feb 18; 6:6351.
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  11. Elliott G, Hong C, Xing X, Zhou X, Li D, Coarfa C, Bell RJ, Maire CL, Ligon KL, Sigaroudinia M, Gascard P, Tlsty TD, Harris RA, Schalkwyk LC, Bilenky M, Mill J, Farnham PJ, Kellis M, Marra MA, Milosavljevic A, Hirst M, Stormo GD, Wang T, Costello JF. Intermediate DNA methylation is a conserved signature of genome regulation. Nat Commun. 2015 Feb 18; 6:6363.
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  12. Lowdon RF, Zhang B, Bilenky M, Mauro T, Li D, Gascard P, Sigaroudinia M, Farnham PJ, Bastian BC, Tlsty TD, Marra MA, Hirst M, Costello JF, Wang T, Cheng JB. Regulatory network decoded from epigenomes of surface ectoderm-derived cell types. Nat Commun. 2014 Nov 25; 5:5442.
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  13. DeFilippis RA, Fordyce C, Patten K, Chang H, Zhao J, Fontenay GV, Kerlikowske K, Parvin B, Tlsty TD. Stress signaling from human mammary epithelial cells contributes to phenotypes of mammographic density. Cancer Res. 2014 Sep 15; 74(18):5032-5044.
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  14. Liao D, Tlsty TD. Evolutionary game theory for physical and biological scientists. I. Training and validating population dynamics equations. Interface Focus. 2014 Aug 06; 4(4):20140037.
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  15. Liao D, Tlsty TD. Evolutionary game theory for physical and biological scientists. II. Population dynamics equations can be associated with interpretations. Interface Focus. 2014 Aug 06; 4(4):20140038.
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  16. Wu A, Liao D, Tlsty TD, Sturm JC, Austin RH. Game theory in the death galaxy: interaction of cancer and stromal cells in tumour microenvironment. Interface Focus. 2014 Aug 06; 4(4):20140028.
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  17. Wu A, Loutherback K, Lambert G, Estévez-Salmerón L, Tlsty TD, Austin RH, Sturm JC. Cell motility and drug gradients in the emergence of resistance to chemotherapy. Proc Natl Acad Sci U S A. 2013 Oct 01; 110(40):16103-8.
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  18. Zhang B, Zhou Y, Lin N, Lowdon RF, Hong C, Nagarajan RP, Cheng JB, Li D, Stevens M, Lee HJ, Xing X, Zhou J, Sundaram V, Elliott G, Gu J, Shi T, Gascard P, Sigaroudinia M, Tlsty TD, Kadlecek T, Weiss A, O'Geen H, Farnham PJ, Maire CL, Ligon KL, Madden PA, Tam A, Moore R, Hirst M, Marra MA, Zhang B, Costello JF, Wang T. Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm. Genome Res. 2013 Sep; 23(9):1522-40.
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  19. Xie M, Hong C, Zhang B, Lowdon RF, Xing X, Li D, Zhou X, Lee HJ, Maire CL, Ligon KL, Gascard P, Sigaroudinia M, Tlsty TD, Kadlecek T, Weiss A, O'Geen H, Farnham PJ, Madden PA, Mungall AJ, Tam A, Kamoh B, Cho S, Moore R, Hirst M, Marra MA, Costello JF, Wang T. DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. Nat Genet. 2013 Jul; 45(7):836-41.
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  20. López-Díaz FJ, Gascard P, Balakrishnan SK, Zhao J, Del Rincon SV, Spruck C, Tlsty TD, Emerson BM. Coordinate transcriptional and translational repression of p53 by TGF-ß1 impairs the stress response. Mol Cell. 2013 May 23; 50(4):552-64.
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