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.

Research Funding

  • January 19, 2016 - December 31, 2022 - Plastic States Associated with Cellular Stress and Malignancy: Insights for Prevention and Treatment of Lethal Metaplastic Cancers, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R35CA197694
  • July 1, 2015 - June 30, 2020 - CD36-dependent stromal signaling orchestrates acquisition of pro-tumorigenic phenotypes, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA197977
  • April 1, 2015 - March 31, 2020 - Using Stromal Markers to Improve Risk Stratification of Ductal Carcinoma in Situ, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA187800
  • September 28, 2009 - July 31, 2014 - Explosive Evolution Under Stress: The Driving Forces of Cancer Dynamics (Main), Co-Investigator. Sponsor: NIH, Sponsor Award ID: U54CA143803

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

Selected Publications

  1. Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, Fearon D, Greten FR, Hingorani SR, Hunter T, Hynes RO, Jain RK, Janowitz T, Jorgensen C, Kimmelman AC, Kolonin MG, Maki RG, Powers RS, Puré E, Ramirez DC, Scherz-Shouval R, Sherman MH, Stewart S, Tlsty TD, Tuveson DA, Watt FM, Weaver V, Weeraratna AT, Werb Z A framework for advancing our understanding of cancer-associated fibroblasts.  View on PubMed
  2. Tlsty TD, Gascard P Stromal directives can control cancer.  View on PubMed
  3. Blagoev KB, Ting DT, Levine H, Saenger Y, Tlsty TD, Sun B Introducing cancer convergence.  View on PubMed
  4. Fuhrmann A, Banisadr A, Beri P, Tlsty TD, Engler AJ Metastatic State of Cancer Cells May Be Indicated by Adhesion Strength.  View on PubMed
  5. 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.  View on PubMed
  6. 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.  View on PubMed
  7. Gascard P, Tlsty TD Carcinoma-associated fibroblasts: orchestrating the composition of malignancy.  View on PubMed
  8. 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.  View on PubMed
  9. Drake CR, Estévez-Salmerón L, Gascard P, Shen Y, Tlsty TD, Jones EF Towards aspirin-inspired self-immolating molecules which target the cyclooxygenases.  View on PubMed
  10. , 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.  View on PubMed
  11. 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.  View on PubMed
  12. 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.  View on PubMed
  13. 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.  View on PubMed
  14. 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.  View on PubMed
  15. Liao D, Tlsty TD Evolutionary game theory for physical and biological scientists. I. Training and validating population dynamics equations.  View on PubMed
  16. Liao D, Tlsty TD Evolutionary game theory for physical and biological scientists. II. Population dynamics equations can be associated with interpretations.  View on PubMed
  17. 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.  View on PubMed
  18. 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.  View on PubMed
  19. 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.  View on PubMed
  20. 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.  View on PubMed

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