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

  • August 5, 1999 - May 31, 2023 - Cancer Center Support Grant , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P30CA082103
  • 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, Sponsor Award ID: R35CA197694
  • July 1, 2015 - December 31, 2015 - CD36-dependent stromal signaling orchestrates acquisition of pro-tumorigenic phenotypes , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA197977
  • April 1, 2015 - December 31, 2015 - Using Stromal Markers to Improve Risk Stratification of Ductal Carcinoma in Situ , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA187800

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

Honors & Awards

  • 2021 Blaffer Distinguished Lecture, MD Anderson Cancer Center
  • 2019 Winner of the “Grand Challenge” competition sponsored by Cancer Research UK (CRUK), an ambitious international funding initiative that aims to answer some of the biggest open questions in cancer. Tlsty’s international team will receive £20 Million (U.S. $26 million) to uncover how chronic inflammation causes cancer.
  • 2015 Outstanding Investigator Award from National Cancer Institute  
  • 2014 Blaffer Distinguished Lecture, MD Anderson Cancer Center
  • 2012 Nakahara Award (Princess Takamatsu Cancer Research Foundation)
  • 2011 KOMEN Scholar
  • 2003 NCI Knudson Award
  • 2001 Elected Fellow of AAAS
  • 2001 AVON scholar

Selected Publications

  1. Strasser MK, Gibbs DL, Gascard P, Bons J, Hickey JW, Schürch CM, Tan Y, Black S, Chu P, Ozkan A, Basisty N, Sangwan V, Rose J, Shah S, Camilleri-Broet S, Fiset PO, Bertos N, Berube J, Djambazian H, Li R, Oikonomopoulos S, Fels-Elliott DR, Vernovsky S, Shimshoni E, Collyar D, Russell A, Ragoussis I, Stachler M, Goldenring JR, McDonald S, Ingber DE, Schilling B, Nolan GP, Tlsty TD, Huang S, Ferri LE. Concerted epithelial and stromal changes during progression of Barrett's Esophagus to invasive adenocarcinoma exposed by multi-scale, multi-omics analysis. bioRxiv. 2023 Jun 11.  View on PubMed
  2. Lee SH, Contreras Panta EW, Gibbs D, Won Y, Min J, Zhang C, Roland JT, Hong SH, Sohn Y, Krystofiak E, Jang B, Ferri L, Sangwan V, Ragoussis J, Camilleri-Broët S, Caruso J, Chen-Tanyolac C, Strasser M, Gascard P, Tlsty TD, Huang S, Choi E, Goldenring JR. Apposition of Fibroblasts With Metaplastic Gastric Cells Promotes Dysplastic Transition. Gastroenterology. 2023 08; 165(2):374-390.  View on PubMed
  3. Bons J, Pan D, Shah S, Bai R, Chen-Tanyolac C, Wang X, Elliott DRF, Urisman A, O'Broin A, Basisty N, Rose J, Sangwan V, Camilleri-Broët S, Tankel J, Gascard P, Ferri L, Tlsty TD, Schilling B. Data-independent acquisition and quantification of extracellular matrix from human lung in chronic inflammation-associated carcinomas. Proteomics. 2023 04; 23(7-8):e2200021.  View on PubMed
  4. Shin J, Parker MFL, Zhu I, Alanizi A, Rodriguez CI, Liu R, Watchmaker PB, Kalita M, Blecha J, Luu J, Wright B, Lapi SE, Flavell RR, Okada H, Tlsty TD, Roybal KT, Wilson DM. Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma. J Nucl Med. 2023 01; 64(1):137-144.  View on PubMed
  5. Murrow LM, Weber RJ, Caruso JA, McGinnis CS, Phong K, Gascard P, Rabadam G, Borowsky AD, Desai TA, Thomson M, Tlsty T, Gartner ZJ. Mapping hormone-regulated cell-cell interaction networks in the human breast at single-cell resolution. Cell Syst. 2022 08 17; 13(8):644-664.e8.  View on PubMed
  6. Caruso JA, Tlsty TD. Remaining true to one's identity. Nat Aging. 2021 09; 1(9):757-759.  View on PubMed
  7. 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. Nat Rev Cancer. 2020 03; 20(3):174-186.  View on PubMed
  8. Tlsty TD, Gascard P. Stromal directives can control cancer. Science. 2019 07 12; 365(6449):122-123.  View on PubMed
  9. Blagoev KB, Ting DT, Levine H, Saenger Y, Tlsty TD, Sun B. Introducing cancer convergence. Cancer Converg. 2017; 1(1):3.  View on PubMed
  10. 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.  View on PubMed
  11. 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.  View on PubMed
  12. 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.  View on PubMed
  13. Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev. 2016 05 01; 30(9):1002-19.  View on PubMed
  14. 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.  View on PubMed
  15. 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.  View on PubMed
  16. Roadmap Epigenomics Consortium, 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.  View on PubMed
  17. 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.  View on PubMed
  18. 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.  View on PubMed
  19. 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.  View on PubMed
  20. 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.  View on PubMed

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