Photo of David T. Breault,  MD, PhD

David T. Breault, MD, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2863
Fax: (617) 730-0244


david.breault@childrens.harvard.edu

David T. Breault, MD, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Pediatrics, Harvard Medical School
  • Associate, Medicine, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are pursuing the hypothesis that slowly cycling and rapidly cycling intestinal stem cells exhibit distinctly different responses to tumor initiating signals. Preliminary results indicate that adenoma formation does not arise from slowly cycling (quiescent) stem cells. Ongoing work is focused on defining the mechanism underlying this tumor suppressor state, including analysis of gene expression and microRNA signatures.

Comparative analysis of rapidly and slowly cycling stem cells will provide unique insight into the mechanisms regulating the initial steps of cancer initiation.

Publications from Harvard Catalyst Profiles

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  • Sebastian C, Ferrer C, Serra M, Choi JE, Ducano N, Mira A, Shah MS, Stopka SA, Perciaccante AJ, Isella C, Moya-Rull D, Vara-Messler M, Giordano S, Maldi E, Desai N, Capen DE, Medico E, Cetinbas M, Sadreyev RI, Brown D, Rivera MN, Sapino A, Breault DT, Agar NYR, Mostoslavsky R. A non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine. Nat Commun 2022; 13:1503. PubMed
  • Cambra HM, Tallapragada NP, Mannam P, Breault DT, Klein AM. Triple-Decker Sandwich Cultures of Intestinal Organoids for Long-Term Live Imaging, Uniform Perturbation, and Statistical Sampling. Curr Protoc 2022; 2:e330. PubMed
  • Zeve D, Stas E, de Sousa Casal J, Mannam P, Qi W, Yin X, Dubois S, Shah MS, Syverson EP, Hafner S, Karp JM, Carlone DL, Ordovas-Montanes J, Breault DT. Robust differentiation of human enteroendocrine cells from intestinal stem cells. Nat Commun 2022; 13:261. PubMed
  • Zhang J, Hernandez-Gordillo V, Trapecar M, Wright C, Taketani M, Schneider K, Chen WLK, Stas E, Breault DT, Carrier RL, Voigt CA, Griffith LG. Coculture of primary human colon monolayer with human gut bacteria. Nat Protoc 2021; 16:3874-3900. PubMed
  • Leng S, Carlone DL, Guagliardo NA, Barrett PQ, Breault DT. Rosette morphology in zona glomerulosa formation and function. Mol Cell Endocrinol 2021; 530:111287. PubMed
  • Carlone DL, Riba-Wolman RD, Deary LT, Tovaglieri A, Jiang L, Ambruzs DM, Mead BE, Shah MS, Lengner CJ, Jaenisch R, Breault DT. Telomerase expression marks transitional growth-associated skeletal progenitor/stem cells. Stem Cells 2021; 39:296-305. PubMed
  • Zhang J, Huang YJ, Yoon JY, Kemmitt J, Wright C, Schneider K, Sphabmixay P, Hernandez-Gordillo V, Holcomb SJ, Bhushan B, Rohatgi G, Benton K, Carpenter D, Kester JC, Eng G, Breault DT, Yilmaz O, Taketani M, Voigt CA, Carrier RL, Trumper DL, Griffith LG. Primary human colonic mucosal barrier crosstalk with super oxygen-sensitive in continuous culture. 2021; 2:74-98.e9. PubMed
  • He A, Huang Y, Cheng W, Zhang D, He W, Bai Y, Gu C, Ma Z, He Z, Si G, Chen B, Breault DT, Dong M, Xiang D. Organoid culture system for patient-derived lung metastatic osteosarcoma. Med Oncol 2020; 37:105. PubMed
  • Hernandez-Gordillo V, Kassis T, Lampejo A, Choi G, Gamboa ME, Gnecco JS, Brown A, Breault DT, Carrier R, Griffith LG. Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids. Biomaterials 2020; 254:120125. PubMed
  • Borges KS, Pignatti E, Leng S, Kariyawasam D, Ruiz-Babot G, Ramalho FS, Taketo MM, Carlone DL, Breault DT. Wnt/β-catenin activation cooperates with loss of p53 to cause adrenocortical carcinoma in mice. Oncogene 2020. PubMed
  • Pignatti E, Leng S, Yuchi Y, Borges KS, Guagliardo NA, Shah MS, Ruiz-Babot G, Kariyawasam D, Taketo MM, Miao J, Barrett PQ, Carlone DL, Breault DT. Beta-Catenin Causes Adrenal Hyperplasia by Blocking Zonal Transdifferentiation. Cell Rep 2020; 31:107524. PubMed
  • Leng S, Pignatti E, Khetani RS, Shah MS, Xu S, Miao J, Taketo MM, Beuschlein F, Barrett PQ, Carlone DL, Breault DT. β-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis. Nat Commun 2020; 11:1680. PubMed
  • Guagliardo NA, Klein PM, Gancayco CA, Lu A, Leng S, Makarem RR, Cho C, Rusin CG, Breault DT, Barrett PQ, Beenhakker MP. Angiotensin II induces coordinated calcium bursts in aldosterone-producing adrenal rosettes. Nat Commun 2020; 11:1679. PubMed
  • Sontheimer-Phelps A, Chou DB, Tovaglieri A, Ferrante TC, Duckworth T, Fadel C, Frismantas V, Sutherland AD, Jalili-Firoozinezhad S, Kasendra M, Stas E, Weaver JC, Richmond CA, Levy O, Prantil-Baun R, Breault DT, Ingber DE. Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology. Cell Mol Gastroenterol Hepatol 2019. PubMed
  • Jalili-Firoozinezhad S, Gazzaniga FS, Calamari EL, Camacho DM, Fadel CW, Bein A, Swenor B, Nestor B, Cronce MJ, Tovaglieri A, Levy O, Gregory KE, Breault DT, Cabral JMS, Kasper DL, Novak R, Ingber DE. A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip. Nat Biomed Eng 2019. PubMed
  • Basham KJ, Rodriguez S, Turcu AF, Lerario AM, Logan CY, Rysztak MR, Gomez-Sanchez CE, Breault DT, Koo BK, Clevers H, Nusse R, Val P, Hammer GD. A ZNRF3-dependent Wnt/β-catenin signaling gradient is required for adrenal homeostasis. Genes Dev 2019; 33:209-220. PubMed
  • Konnikova L, Boschetti G, Rahman A, Mitsialis V, Lord J, Richmond C, Tomov VT, Gordon W, Jelinsky S, Canavan J, Liss A, Wall S, Field M, Zhou F, Goldsmith JD, Bewtra M, Breault DT, Merad M, Snapper SB. High-dimensional immune phenotyping and transcriptional analyses reveal robust recovery of viable human immune and epithelial cells from frozen gastrointestinal tissue. Mucosal Immunol 2018. PubMed
  • Richardson G, Sage A, Bennaceur K, Al Zhrany N, Coelho-Lima J, Dookun E, Draganova L, Saretzki G, Breault DT, Mallat Z, Spyridopoulos I. Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells. Arterioscler Thromb Vasc Biol 2018. PubMed
  • Lyons J, Ghazi PC, Starchenko A, Tovaglieri A, Baldwin KR, Poulin EJ, Gierut JJ, Genetti C, Yajnik V, Breault DT, Lauffenburger DA, Haigis KM. The colonic epithelium plays an active role in promoting colitis by shaping the tissue cytokine profile. PLoS Biol. 2018; 16:e2002417. PubMed
  • Kasendra M, Tovaglieri A, Sontheimer-Phelps A, Jalili-Firoozinezhad S, Bein A, Chalkiadaki A, Scholl W, Zhang C, Rickner H, Richmond CA, Li H, Breault DT, Ingber DE. Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids. Sci Rep 2018; 8:2871. PubMed
  • Richmond CA, Rickner H, Shah MS, Ediger T, Deary L, Zhou F, Tovaglieri A, Carlone DL, Breault DT. JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation. Stem Cell Reports 2018; 10:17-26. PubMed
  • Richmond CA, Breault DT. Move Over Caco-2 Cells: Human-Induced Organoids Meet Gut-on-a-Chip. Cell Mol Gastroenterol Hepatol 2018; 5:634-635. PubMed
  • Ong YR, Cousins FL, Yang X, Mushafi AAAA, Breault DT, Gargett CE, Deane JA. Bone Marrow Stem Cells Do Not Contribute to Endometrial Cell Lineages in Chimeric Mouse Models. Stem Cells 2017. PubMed
  • Yan KS, Gevaert O, Zheng GXY, Anchang B, Probert CS, Larkin KA, Davies PS, Cheng ZF, Kaddis JS, Han A, Roelf K, Calderon RI, Cynn E, Hu X, Mandleywala K, Wilhelmy J, Grimes SM, Corney DC, Boutet SC, Terry JM, Belgrader P, Ziraldo SB, Mikkelsen TS, Wang F, von Furstenberg RJ, Smith NR, Chandrakesan P, May R, Chrissy MAS, Jain R, Cartwright CA, Niland JC, Hong YK, Carrington J, Breault DT, Epstein J, Houchen CW, Lynch JP, Martin MG, Plevritis SK, Curtis C, Ji HP, Li L, Henning SJ, Wong MH, Kuo CJ. Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity. Cell Stem Cell 2017; 21:78-90.e6. PubMed
  • Stokes K, Cooke A, Chang H, Weaver DR, Breault DT, Karpowicz P. The Circadian Clock Gene BMAL1 Coordinates Intestinal Regeneration. Cell Mol Gastroenterol Hepatol 2017; 4:95-114. PubMed
  • Tao L, Zhang J, Meraner P, Tovaglieri A, Wu X, Gerhard R, Zhang X, Stallcup WB, Miao J, He X, Hurdle JG, Breault DT, Brass AL, Dong M. Frizzled proteins are colonic epithelial receptors for C. difficile toxin B. Nature 2016. PubMed
  • Richmond CA, Shah MS, Carlone DL, Breault DT. An enduring role for quiescent stem cells. Dev Dyn 2016; 245:718-26. PubMed
  • Deane JA, Ong YR, Cain JE, Jayasekara WS, Tiwari A, Carlone DL, Watkins DN, Breault DT, Gargett CE. The mouse endometrium contains epithelial, endothelial and leucocyte populations expressing the stem cell marker telomerase reverse transcriptase. 2016; 22:272-84. PubMed
  • Ariyachet C, Tovaglieri A, Xiang G, Lu J, Shah MS, Richmond CA, Verbeke C, Melton DA, Stanger BZ, Mooney D, Shivdasani RA, Mahony S, Xia Q, Breault DT, Zhou Q. Reprogrammed Stomach Tissue as a Renewable Source of Functional β Cells for Blood Glucose Regulation. Cell Stem Cell 2016; 18:410-21. PubMed
  • Barrett PQ, Guagliardo NA, Klein PM, Hu C, Breault DT, Beenhakker MP. Role of voltage-gated calcium channels in the regulation of aldosterone production from zona glomerulosa cells of the adrenal cortex. J Physiol 2016. PubMed
  • Richmond CA, Shah MS, Deary LT, Trotier DC, Thomas H, Ambruzs DM, Jiang L, Whiles BB, Rickner HD, Montgomery RK, Tovaglieri A, Carlone DL, Breault DT. Dormant Intestinal Stem Cells Are Regulated by PTEN and Nutritional Status. Cell Rep 2015; 13:2403-11. PubMed
  • Richmond CA, Shah MS, Carlone DL, Breault DT. Factors regulating quiescent stem cells: Insights from the intestine and other self-renewing tissues. J Physiol 2015. PubMed
  • San Roman AK, Tovaglieri A, Breault DT, Shivdasani RA. Distinct Processes and Transcriptional Targets Underlie CDX2 Requirements in Intestinal Stem Cells and Differentiated Villus Cells. Stem Cell Reports 2015; 5:673-81. PubMed
  • Gierut JJ, Lyons J, Shah MS, Genetti C, Breault DT, Haigis KM. Oncogenic K-Ras promotes proliferation in quiescent intestinal stem cells. 2015; 15:165-71. PubMed
  • Bennaceur K, Atwill M, Al Zhrany N, Hoffmann J, Keavney B, Breault D, Richardson G, von Zglinicki T, Saretzki G, Spyridopoulos I. Atorvastatin induces T cell proliferation by a telomerase reverse transcriptase (TERT) mediated mechanism. Atherosclerosis 2014; 236:312-20. PubMed
  • Meeson A, Fuller A, Breault DT, Owens WA, Richardson GD. Optimised protocols for the identification of the murine cardiac side population. Stem Cell Rev 2013. PubMed
  • Freedman BD, Kempna PB, Carlone DL, Shah MS, Guagliardo NA, Barrett PQ, Gomez-Sanchez CE, Majzoub JA, Breault DT. Adrenocortical zonation results from lineage conversion of differentiated zona glomerulosa cells. Dev Cell 2013; 26:666-73. PubMed
  • Richardson GD, Breault D, Horrocks G, Cormack S, Hole N, Owens WA. Telomerase expression in the mammalian heart. FASEB J. 2012. PubMed
  • Kodama Y, Noda A, Booth C, Breault D, Suda T, Hendry J, Shinohara T, Rübe C, Nishimura EK, Mitani H, Nakamura N, Niwa O. International workshop: radiation effects on mutation in somatic and germline stem cells. Int J Radiat Biol 2012; 88:501-6. PubMed
  • Carlone DL, Breault DT. Tales from the crypt: the expanding role of slow cycling intestinal stem cells. Cell Stem Cell 2012; 10:2-4. PubMed
  • Song J, Czerniak S, Wang T, Ying W, Carlone DL, Breault DT, Humphreys BD. Characterization and fate of telomerase-expressing epithelia during kidney repair. J Am Soc Nephrol 2011; 22:2256-65. PubMed
  • Carlone DL, Breault DT. Slowly cycling versus rapidly cycling intestinal stem cells: distinct roles or redundancy. Cell Cycle 2011; 10:723-4. PubMed
  • Montgomery RK, Carlone DL, Richmond CA, Farilla L, Kranendonk ME, Henderson DE, Baffour-Awuah NY, Ambruzs DM, Fogli LK, Algra S, Breault DT. Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc Natl Acad Sci U S A 2011; 108:179-84. PubMed
  • Richmond CA, Breault DT. Regulation of gene expression in the intestinal epithelium. 2010; 96:207-29. PubMed
  • Breault DT,Min IM,Carlone DL,Farilla LG,Ambruzs DM,Henderson DE,Algra S,Montgomery RK,Wagers AJ,Hole N. Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells. Proc Natl Acad Sci U S A 2008; 105:10420-5. PubMed
  • Stadtfeld M, Maherali N, Breault DT, Hochedlinger K. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2008; 2:230-40. PubMed
  • Nelms BD, Waldron L, Barrera LA, Weflen AW, Goettel JA, Guo G, Montgomery RK, Neutra MR, Breault DT, Snapper SB, Orkin SH, Bulyk ML, Huttenhower C, Lencer WI. CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell types. Genome Biol ; 17:201. PubMed
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