Purushothama Rao Tata, Ph.D. (University of Ulm, Ulm, Germany)
Associate Professor of Cell Biology
Email: purushothamarao.tata@duke.edu
308 Nanaline Duke Bldg., Box 3709
Duke University School of Medicine
Durham, NC 27710
Telephone: 919-684-0624
Fax: 919-684-8090
Tata Lab Website
Genetic and epigenetic basis of cell identity and plasticity in regeneration and tumorigenesis
Many human diseases are a result of either a deficit or surfeit in the quantity or functionality of particular cell types. Although the principles of cell fate specification during embryogenesis are rather well documented, it is unclear what mechanisms are used to maintain cell identity and appropriate cell numbers in adult tissues. While the cell autonomous molecular processes defining cell states in both physiological and pathological conditions are being defined with increasing precision using genome-wide inventories, the question of when and how individual cell types interact with one another to maintain their identity remains largely unresolved. In this context Tata lab studies:
i) Defining the cellular heterogeneity and the lineage hierarchies in epithelial tissues
ii) How do individual cells maintain their identity under steady state conditions and in the context of regeneration?
iii) The genetic and epigenetic basis of tissue plasticity associated with regeneration and tumorigenesis
Tata lab focuses on understanding the ensemble properties of tissues in the context of development, homeostasis, regeneration and tumorigenesis in diverse epithelial tissues including lung. We use mouse models of disease that recapitulates the human disease pathology. We utilize genetic, live imaging, cell biological and next generation sequencing technologies including single-cell RNA sequencing to study the behavior of tissues at single cell level.
PUBLICATIONS
Katsura H*, Sontake V*, Tata A*, Kobayashi Y*, Edwards CE*, Heaton BE, Konkimalla A, Asakura T, Mikami Y, Fritch EJ, Lee PJ, Heaton NS, Boucher RC, Randell SH, Baric RS, Tata PR. Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction. Cell Stem Cell. 2020 Oct 21; PMCID: PMC7577733 (* equal contribution).
Kobayashi Y*, Tata A*, Konkimalla A, Katsura H, Lee RF, Ou J, Banovich NE, Kropski JA, Tata PR. Persistence of a novel regeneration-associated transitional cell state in pulmonary fibrosis. Nat Cell Biol. 2020 Jul 13; PMCID: PMC7461628. (* equal contribution)
Hou YJ, Okuda K, Edwards CE, Martinez DR, Asakura T, Dinnon KH, Kato T, Lee RE, Yount BL, Mascenik TM, Chen G, Olivier KN, Ghio A, Tse LV, Leist SR, Gralinski LE, Schäfer A, Dang H, Gilmore R, Nakano S, Sun L, Fulcher ML, Livraghi-Butrico A, Nicely NI, Cameron M, Cameron C, Kelvin DJ, de Silva A, Margolis DM, Markmann A, Bartelt L, Zumwalt R, Martinez FJ, Salvatore SP, Borczuk A, Tata PR, Sontake V, Kimple A, Jaspers I, O’Neal WK, Randell SH, Boucher RC, Baric RS. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell. 2020 May 27; PMCID: PMC7250779
Uezu A, Hisey E, Kobayashi Y, Gao Y, Bradshaw TW, Devlin P, Rodriguiz R, Tata PR, Soderling S. Essential role for InSyn1 in dystroglycan complex integrity and cognitive behaviors in mice. eLife. 2019 Dec 12;8. PMCID: PMC6944460.
Katsura H, Kobayashi Y, Tata PR*, Hogan BLM*. IL-1 and TNFα Contribute to the Inflammatory Niche to Enhance Alveolar Regeneration. Stem Cell Reports. 2019 Apr 9;12(4):657-666; PMCID: PMC6450459. (* Co-corresponding autor).
Khatri A, Kraft BD, Tata PR, Randell SH, Piantadosi CA, Pendergast AM. ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia. Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1603-1612. PMCID: PMC6358689.
Tata A, Kobayashi Y, Chow RD, Tran J, Desai A, Massri AJ, McCord TJ, Gunn MD, Tata PR. Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury. Cell Stem Cell. 2018 May 3;22(5):668-683.e6. PMCID: PMC5935539.
Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, Yuan F, Chen S, Leung HM, Villoria J, Rogel N, Burgin G, Tsankov AM, Waghray A, Slyper M, Waldman J, Nguyen L, Dionne D, Rozenblatt-Rosen O, Tata PR, Mou H, Shivaraju M, Bihler H, Mense M, Tearney GJ, Rowe SM, Engelhardt JF, Regev A, Rajagopal J. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature. 2018 Aug;560(7718):319–324. PMCID: PMC6295155.
Saladi SV, Ross K, Karaayvaz M, Tata PR, Mou H, Rajagopal J, Ramaswamy S, Ellisen LW. ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis. Cancer Cell. 2017 09;31(1):35–49. PMCID: PMC5225026.
Tata PR* §, Chow RDz§, Saladi SV, Tata A, Konkimalla A, Bara A, Montoro D, Hariri LP, Shih AR, Mino-Kenudson M, Mou H, Kimura S, Ellisen LW, Rajagopal J. Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity. Developmental Cell. 2018 26;44(6):679-693.e5. PMCID: PMC5875457 (*Corresponding author; § equal contribution).
Taylor MS, Chivukula RR, Myers LC, Jeck WR, Tata PR, O’Donnell WJ, Farver CF, Thompson BT, Rajagopal J, Kradin RL. Delayed Alveolar Epithelialization: A Distinct Pathology in Diffuse Acute Lung Injury. Am J Respir Crit Care Med. 2018 Feb 15;197(4):522–524. PMCID: PMC5821904.
Taylor MS, Chivukula RR, Myers LC, Jeck WR, Waghray A, Tata PR, Selig MK, O’Donnell WJ, Farver CF, Thompson BT, Rajagopal J, Kradin RL. A Conserved Distal Lung Regenerative Pathway in Acute Lung Injury. American Journal of Pathology. 2018 May;188(5):1149–1160. PMCID: PMC5906746.
Hempel A, Kühl SJ, Rothe M, Tata PR, Sirbu IO, Vainio SJ, Kühl M. The CapZ interacting protein Rcsd1 is required for cardiogenesis downstream of Wnt11a in Xenopus laevis. Developmental Biology. 2017 01;424(1):28–39. PMID: 28237811.
Mou H, Vinarsky V, Tata PR, Brazauskas K, Choi SH, Crooke AK, Zhang B, Solomon GM, Turner B, Bihler H, Harrington J, Lapey A, Channick C, Keyes C, Freund A, Artandi S, Mense M, Rowe S, Engelhardt JF, Hsu Y-C, Rajagopal J. Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells. Cell Stem Cell. 2016 04;19(2):217–231. PMCID: PMC4975684.
Pardo-Saganta A, Law BM, Tata PR, Villoria J, Saez B, Mou H, Zhao R, Rajagopal J. Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations. Cell Stem Cell. 2015 Feb 5;16(2):184–197. PMCID: PMC4334442.
Pardo-Saganta A§, Tata PR§, Law BM, Saez B, Chow RD-W, Prabhu M, Gridley T, Rajagopal J. Parent stem cells can serve as niches for their daughter cells. Nature. 2015 Jul 30;523(7562):597–601. PMCID: PMC4521991 (§ equal contribution).
Tata PR, Mou H, Pardo-Saganta A, Zhao R, Prabhu M, Law BM, Vinarsky V, Cho JL, Breton S, Sahay A, Medoff BD, Rajagopal J. Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature. 2013 Nov 14; 503(7475):218-23. PMCID: PMC4035230.
Tata PR, Pardo-Saganta A, Prabhu M, Vinarsky V, Law BM, Fontaine BA, Tager AM, Rajagopal J. Airway-specific inducible transgene expression using aerosolized doxycycline. Am J Respir Cell Mol Biol. 2013 Dec;49(6):1048–1056. PMCID: PMC3931107.
Watanabe H, Francis JM, Woo MS, Etemad B, Lin W, Fries DF, Peng S, Snyder EL, Tata PR, Izzo F, Schinzel AC, Cho J, Hammerman PS, Verhaak RG, Hahn WC, Rajagopal J, Jacks T, Meyerson M. Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target. Genes & Development. 2013 Jan 15;27(2):197–210. PMCID: PMC3566312.
Weidgang CE§, Russell R§, Tata PR§, Kühl SJ, Illing A, Müller M, Lin Q, Brunner C, Boeckers TM, Bauer K, Kartikasari AER, Guo Y, Radenz M, Bernemann C, Weiß M, Seufferlein T, Zenke M, Iacovino M, Kyba M, Schöler HR, Kühl M, Liebau S, Kleger A. TBX3 Directs Cell-Fate Decision toward Mesendoderm. Stem Cell Reports. 2013;1(3):248–265. PMCID: PMC3849240 (§ equal contribution).
Tata PR, Tata NR, Kühl M, Sirbu IO. Identification of a novel epigenetic regulatory region within the pluripotency associated microRNA cluster, EEmiRC. Nucleic Acids Research. 2011 May;39(9):3574–3581. PMCID: PMC3089473
Complete List of Published Work In My Bibliography:
https://www.ncbi.nlm.nih.gov/myncbi/purushothama%20rao.tata.2/bibliography/public/