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Thea Tlsty, PhD

Research and Clinical Interests

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.

Selected Publications

  • 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, 28: 1923-1932, 2016
  • Gascard P, Tlsty TD. “Carcinoma-associated fibroblasts: orchestrating the composition of malignancy“ Genes Dev 30: 1002-1019, 2016
  • 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 157: 351-361, 2016
  • 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 74: 5032-5044, 2014
  • Roy S, Gascard P, Dumont N, Zhao J, Pan D, Petrie S, Margeta M, Tlsty TD. “Rare somatic cells from human breast tissue exhibit extensive lineage plasticity“ Proc Natl Acad Sci U S A 110: 4598-4603, 2013
  • Dumont N, Liu B, Defilippis RA, Chang H, Rabban JT, Karnezis AN, Tjoe JA, Marx J, Parvin B, Tlsty TD. “Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics“ Neoplasia 15: 249-262, 2013
  • Liao D, Estévez-Salmerón L, Tlsty TD. “Conceptualizing a tool to optimize therapy based on dynamic heterogeneity“ Phys Biol. 9: 065005, 2012
  • DeFilippis RA, Chang H, Dumont N, Rabban JT, Chen YY, Fontenay GV, Berman HK, Gauthier ML, Zhao J, Hu D, Marx JJ, Tjoe JA, Ziv E, Febbraio M, Kerlikowske K, Parvin B, Tlsty TD. “CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues“ Cancer Discov 2: 826-839, 2012
  • Fordyce CA, Patten KT, Fessenden TB, DeFilippis R, Hwang ES, Zhao J, Tlsty TD. “Cell-extrinsic consequences of epithelial stress: activation of protumorigenic tissue phenotypes“ Breast Cancer Res 14:R155, 2012
  • Dvorak HF, Weaver VM, Tlsty TD, Bergers G.“Tumor microenvironment and progression“ J Surg Oncol 103: 468-474, 2011
  • Lambert G, Estévez-Salmeron L, Oh S, Liao D, Emerson BM, Tlsty TD, Austin RH. “An analogy between the evolution of drug resistance in bacterial communities and malignant tissues“ Nat Rev Cancer 11: 375-382, 2011
  • Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K, Ljung BM, Tlsty TD. “Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis“ J Natl Cancer Inst 102: 627-637, 2010
  • Dumont N, Wilson MB, Crawford YG, Reynolds PA, Sigaroudinia M, Tlsty TD. “Sustained induction of epithelial to mesenchymal transition activates DNA methylation of genes silenced in basal-like breast cancers“ Proc Natl Acad Sci U S A 105: 14867-14872, 2008
  • Tlsty T. “Cancer: whispering sweet somethings“ Nature 453: 604-605, 2008
  • Gauthier ML, Berman HK, Miller C, Kozakeiwicz K, Chew K, Moore D, Rabban J, Chen YY, Kerlikowske K, Tlsty TD. “Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors“ Cancer Cell 12: 479-491, 2007
  • Tlsty TD, Coussens LM. “Tumor stroma and regulation of cancer development“ Annu Rev Pathol 1:119-150, 2006
  • Crawford YP, Gauthier M, Joubel A, Mantei K, Kozakiewicz BK, Afshari C, Tlsty TD. “Histologically normal human mammary epithelia with silenced p16INK4a overexpress COX-2, promoting a premalignant program” Cancer Cell 5: 263-73, 2004
  • Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. “Carcinoma-associated Fibroblasts Direct Tumor Progression of Initiated Human Prostatic Epithelium” Cancer Research, 61: 5002-5011, 1999

Selected Awards

  • Fellow of the American Association for the Advancement of Science 2003
  • National Cancer Institute Knudson Award 2003
  • National Cancer Institute, Board of Scientific Advisors

Additional Information

  • Professor
  • Pathology

Specialty Area

Cancer Research

Contact Information

Mailing/Shipping Address:

  • UCSF
  • Thea Tlsty, PhD
  • Pathology, Box 0511
  • 513 Parnassus Avenue, Room HSW-513
  • San Francisco, CA 94143
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