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
  • July 1, 2002 - April 30, 2015 - Regulation of Genomic Instability in Early Breast Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA097214
  • 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
  • August 10, 2006 - February 28, 2013 - Biological Basis of Breast Density and Cancer Risk , Principal Investigator . Sponsor: NIH, Sponsor Award ID: P01CA107584
  • September 18, 2008 - August 31, 2011 - Characterizing the Evolution of Pre-malignant Tissues at High Risk for Malignancy , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA135626
  • July 1, 2006 - June 30, 2010 - Regulation of DNA hypermethylation in human mammary cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA122024
  • February 1, 2000 - January 31, 2004 - FIBROBLAST REGULATION OF HUMAN PROSTATIC CARCINOGENESIS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA083812
  • September 30, 1997 - September 29, 2002 - MECHANISMS OF RADIATION--INDUCED GENOMIC INSTABILITY , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA073952
  • April 1, 1988 - April 30, 2001 - CYCLE-DEPENDENT MECHANISMS OF CHEMICAL CARCINOGENESIS , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01CA042765
  • March 1, 2000 - February 28, 2001 - 10TH INTERNATIONAL P53 WORKSHOP , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13CA085309
  • December 1, 1990 - November 30, 1998 - GENE AMPLIFICATION TO STUDY NEOPLASIA , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA051912
  • March 1, 1993 - January 31, 1997 - CONTROL OF GENOMIC FLUIDITY IN CANCER CELLS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA058413
  • July 1, 1987 - December 31, 1990 - CELLULAR ADAPTATION AND ENVIRONMENTAL CARCINOGENESIS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA043110

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. Moutin EB, Chang L, Giavara G, Mehmed S, Colombé M, Lourenço FC, Skoufou-Papoutsaki MN, Kemp R, Gascard P, Tlsty T, Tourigny DS, Winton DJ. Paired mutation calling and spatial transcriptomics identify cellular neighbourhoods dictating the neoplastic outcome of colitis. Res Sq. 2025 May 08.  View on PubMed
  2. Burton JB, Gascard P, Pan D, Bons J, Bai R, Chen-Tanyolac C, Caruso JA, Hunter CL, Schilling B, Tlsty TD. Proteomic Analysis of Breast Cancer Subtypes Identifies Stromal Contributions that Dictate Aggressive Malignant Behavior. bioRxiv. 2025 Jan 24.  View on PubMed
  3. Caruso JA, Chen-Tanyolac C, Tlsty TD. A hybrid epithelial-mesenchymal transition program enables basal epithelial cells to bypass stress-induced stasis and contributes to a metaplastic breast cancer progenitor state. Breast Cancer Res. 2024 Dec 18; 26(1):184.  View on PubMed
  4. 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. Defining precancer: a grand challenge for the cancer community. Nat Rev Cancer. 2024 Nov; 24(11):792-809.  View on PubMed
  5. Caruso JA, Tlsty TD. An adaptive Epithelial-Mesenchymal Transition Program Enables Basal Epithelial Cells to Bypass Stress-Induced Stasis and Contributes to Metaplastic Breast Cancer Progenitor State. Res Sq. 2024 Sep 27.  View on PubMed
  6. Gascard PD, Wang X, Nosrati M, Kim KB, Kashani-Sabet M, Tlsty TD, Leong SP, Hendrix MJC. Higher Nodal expression is often associated with poorer survival in patients diagnosed with melanoma and treated with anti-PD1 therapy. Pathol Oncol Res. 2024; 30:1611889.  View on PubMed
  7. Moutin EB, Bons J, Giavara G, Lourenco F, Pan D, Burton JB, Shah S, Colombé M, Gascard P, Tlsty T, Schilling B, Winton DJ. Extracellular Matrix Orchestration of Tissue Remodeling in the Chronically Inflamed Mouse Colon. Cell Mol Gastroenterol Hepatol. 2024; 17(4):639-656.  View on PubMed
  8. Caruso JA, Wang X, Murrow LM, Rodriguez CI, Chen-Tanyolac C, Vu L, Chen YY, Gascard P, Gartner ZJ, Kerlikowske K, Tlsty TD. Loss of PPARγ activity characterizes early protumorigenic stromal reprogramming and dictates the therapeutic window of opportunity. Proc Natl Acad Sci U S A. 2023 10 17; 120(42):e2303774120.  View on PubMed
  9. 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
  10. 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
  11. Shimshoni E, Merry GE, Milot ZD, Oh CY, Horvath V, Gould RA, Caruso JA, Chen-Tanyolac C, Gascard P, Sangwan V, Bérubé J, Bailey SD, Hall S, Stachler MD, Ferri L, Tlsty TD, Ingber DE. Epithelial-Stromal Interactions in Barrett's Esophagus Modeled in Human Organ Chips. Gastro Hep Adv. 2023; 2(5):676-680.  View on PubMed
  12. 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
  13. 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
  14. 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
  15. Caruso JA, Tlsty TD. Remaining true to one's identity. Nat Aging. 2021 09; 1(9):757-759.  View on PubMed
  16. 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
  17. Tlsty TD, Gascard P. Stromal directives can control cancer. Science. 2019 07 12; 365(6449):122-123.  View on PubMed
  18. Blagoev KB, Ting DT, Levine H, Saenger Y, Tlsty TD, Sun B. Introducing cancer convergence. Cancer Converg. 2017; 1(1):3.  View on PubMed
  19. 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
  20. 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

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