Thea Tlsty, PhD

Professor
M_Path-Anatomic Path
[email protected]
+1 415 502-6116

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.

Publications

Concerted changes in Epithelium and Stroma: a multi-scale, multi-omics analysis of progression from Barrett's Esophagus to adenocarcinoma.

Developmental cell

Strasser MK, Gibbs DL, Gascard P, Bons J, Hickey JW, Pan D, Caruso JA, Wang X, Chen-Tanyolac C, Bai R, Schürch CM, Tan Y, Black S, Chu P, Ozkan A, Basisty N, Sangwan V, Rose J, Shah S, Burton JB, Camilleri-Broet S, Fiset PO, Bertos N, Berube J, Djambazian H, Li R, Oikonomopoulos S, Elliott DRF, Vernovsky S, Shimshoni E, Collyar D, Russell A, Ragoussis J, Stachler MD, Goldenring JR, McDonald SAC, Ingber DE, Schilling B, Nolan GP, Tlsty TD, Huang S, Ferri LE

Defining precancer: a grand challenge for the cancer community.

Nature reviews. Cancer

Faupel-Badger J, Kohaar I, Bahl M, Chan AT, Campbell JD, Ding L, De Marzo AM, Maitra A, Merrick DT, Hawk ET, Wistuba II, Ghobrial IM, Lippman SM, Lu KH, Lawler M, Kay NE, Tlsty TD, Rebbeck TR, Srivastava S, Precancer Think Tank Team

Concerted epithelial and stromal changes during progression of Barrett's Esophagus to invasive adenocarcinoma exposed by multi-scale, multi-omics analysis.

bioRxiv : the preprint server for biology

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

A framework for advancing our understanding of cancer-associated fibroblasts.

Nature reviews. Cancer

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

Integrative analysis of 111 reference human epigenomes.

Nature

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

Epigenetic and transcriptional determinants of the human breast.

Nature communications

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

A physical sciences network characterization of non-tumorigenic and metastatic cells.

Scientific reports

Agus DB, Alexander JF, Arap W, Ashili S, Aslan JE, Austin RH, Backman V, Bethel KJ, Bonneau R, Chen WC, Chen-Tanyolac C, Choi NC, Curley SA, Dallas M, Damania D, Davies PC, Decuzzi P, Dickinson L, Estevez-Salmeron L, Estrella V, Ferrari M, Fischbach C, Foo J, Fraley SI, Frantz C, Fuhrmann A, Gascard P, Gatenby RA, Geng Y, Gerecht S, Gillies RJ, Godin B, Grady WM, Greenfield A, Hemphill C, Hempstead BL, Hielscher A, Hillis WD, Holland EC, Ibrahim-Hashim A, Jacks T, Johnson RH, Joo A, Katz JE, Kelbauskas L, Kesselman C, King MR, Konstantopoulos K, Kraning-Rush CM, Kuhn P, Kung K, Kwee B, Lakins JN, Lambert G, Liao D, Licht JD, Liphardt JT, Liu L, Lloyd MC, Lyubimova A, Mallick P, Marko J, McCarty OJ, Meldrum DR, Michor F, Mumenthaler SM, Nandakumar V, O'Halloran TV, Oh S, Pasqualini R, Paszek MJ, Philips KG, Poultney CS, Rana K, Reinhart-King CA, Ros R, Semenza GL, Senechal P, Shuler ML, Srinivasan S, Staunton JR, Stypula Y, Subramanian H, Tlsty TD, Tormoen GW, Tseng Y, van Oudenaarden A, Verbridge SS, Wan JC, Weaver VM, Widom J, Will C, Wirtz D, Wojtkowiak J, Wu PH

The clonal and mutational evolution spectrum of primary triple-negative breast cancers.

Nature

Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, Griffith M, Moradian A, Cheng SW, Morin GB, Watson P, Gelmon K, Chia S, Chin SF, Curtis C, Rueda OM, Pharoah PD, Damaraju S, Mackey J, Hoon K, Harkins T, Tadigotla V, Sigaroudinia M, Gascard P, Tlsty T, Costello JF, Meyer IM, Eaves CJ, Wasserman WW, Jones S, Huntsman D, Hirst M, Caldas C, Marra MA, Aparicio S

Benign breast disease and the risk of breast cancer.

The New England journal of medicine

Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, Vierkant RA, Maloney SD, Pankratz VS, Hillman DW, Suman VJ, Johnson J, Blake C, Tlsty T, Vachon CM, Melton LJ, Visscher DW