Thea Tlsty, PhD

Professor
Department of Pathology
+1 415 502-6115

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.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Research Summary: 
Regulation of Genomic Instability in Mammalian Cells

Websites

Featured Publications: 

SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic cells requires CD73.

Cellular signalling

Pan D, Roy S, Gascard P, Zhao J, Chen-Tanyolac C, Tlsty TD

Risk prediction for local versus regional/metastatic tumors after initial ductal carcinoma in situ diagnosis treated by lumpectomy.

Breast cancer research and treatment

Molinaro AM, Sison JD, Ljung BM, Tlsty TD, Kerlikowske K

Stress signaling from human mammary epithelial cells contributes to phenotypes of mammographic density.

Cancer research

DeFilippis RA, Fordyce C, Patten K, Chang H, Zhao J, Fontenay GV, Kerlikowske K, Parvin B, Tlsty TD

Rare somatic cells from human breast tissue exhibit extensive lineage plasticity.

Proceedings of the National Academy of Sciences of the United States of America

Roy S, Gascard P, Dumont N, Zhao J, Pan D, Petrie S, Margeta M, Tlsty TD

Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics.

Neoplasia (New York, N.Y.)

Dumont N, Liu B, Defilippis RA, Chang H, Rabban JT, Karnezis AN, Tjoe JA, Marx J, Parvin B, Tlsty TD

Conceptualizing a tool to optimize therapy based on dynamic heterogeneity.

Physical biology

Liao D, Estévez-Salmerón L, Tlsty TD

CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues.

Cancer discovery

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

Cell-extrinsic consequences of epithelial stress: activation of protumorigenic tissue phenotypes.

Breast cancer research : BCR

Fordyce CA, Patten KT, Fessenden TB, DeFilippis R, Hwang ES, Zhao J, Tlsty TD

Tumor microenvironment and progression.

Journal of surgical oncology

Dvorak HF, Weaver VM, Tlsty TD, Bergers G

An analogy between the evolution of drug resistance in bacterial communities and malignant tissues.

Nature reviews. Cancer

Lambert G, Estévez-Salmeron L, Oh S, Liao D, Emerson BM, Tlsty TD, Austin RH

Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis.

Journal of the National Cancer Institute

Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K, Ljung BM, Tlsty TD

Sustained induction of epithelial to mesenchymal transition activates DNA methylation of genes silenced in basal-like breast cancers.

Proceedings of the National Academy of Sciences of the United States of America

Dumont N, Wilson MB, Crawford YG, Reynolds PA, Sigaroudinia M, Tlsty TD

Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors.

Cancer cell

Gauthier ML, Berman HK, Miller C, Kozakeiwicz K, Chew K, Moore D, Rabban J, Chen YY, Kerlikowske K, Tlsty TD

Tumor stroma and regulation of cancer development.

Annual review of pathology

Tlsty TD, Coussens LM

Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program.

Cancer cell

Crawford YG, Gauthier ML, Joubel A, Mantei K, Kozakiewicz K, Afshari CA, Tlsty TD

Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium.

Cancer research

Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR