Purushothama Rao Tata

Overview:

Lung regeneration
Lung stem cells
Cell plasticity
Organoid models
Lung Fibrosis
Single Cell Biology

Positions:

Assistant Professor of Cell Biology

Cell Biology
School of Medicine

Assistant Professor in Medicine

Medicine, Pulmonary, Allergy, and Critical Care Medicine
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Duke Regeneration Center

Regeneration Next Initiative
School of Medicine

Education:

Ph.D. 2011

University of Ulm (Germany)

Grants:

Mechanisms of submucosal gland cell mediated airway regeneration

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

SOX9 Expression Identifies A Novel Alveolar Stem Cell Population

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Systematic identification of AEC2 cell niche components and the conversion of basal stem cells into AEC2 cells ex vivo

Administered By
Basic Science Departments
Awarded By
United Therapeutics Corporation
Role
Principal Investigator
Start Date
End Date

Image-Seq: A high-density microfluidic trap array for single cell transcriptome analysis coupled with image based phenotyping

Administered By
Mechanical Engineering and Materials Science
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

To define the role of Sox9 and Sox9+ Cells in Alveolar Homeostasis and Regeneration

Administered By
Basic Science Departments
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Epithelial cell plasticity: breaking boundaries and changing landscapes.

Epithelial tissues respond to a wide variety of environmental and genotoxic stresses. As an adaptive mechanism, cells can deviate from their natural paths to acquire new identities, both within and across lineages. Under extreme conditions, epithelial tissues can utilize "shape-shifting" mechanisms whereby they alter their form and function at a tissue-wide scale. Mounting evidence suggests that in order to acquire these alternate tissue identities, cells follow a core set of "tissue logic" principles based on developmental paradigms. Here, we review the terminology and the concepts that have been put forward to describe cell plasticity. We also provide insights into various cell intrinsic and extrinsic factors, including genetic mutations, inflammation, microbiota, and therapeutic agents that contribute to cell plasticity. Additionally, we discuss recent studies that have sought to decode the "syntax" of plasticity-i.e., the cellular and molecular principles through which cells acquire new identities in both homeostatic and malignant epithelial tissues-and how these processes can be manipulated for developing novel cancer therapeutics.
Authors
Tata, A; Chow, RD; Tata, PR
MLA Citation
Tata, Aleksandra, et al. “Epithelial cell plasticity: breaking boundaries and changing landscapes.Embo Reports, vol. 22, no. 7, July 2021, p. e51921. Epmc, doi:10.15252/embr.202051921.
URI
https://scholars.duke.edu/individual/pub1484488
PMID
34096150
Source
epmc
Published In
Embo Reports
Volume
22
Published Date
Start Page
e51921
DOI
10.15252/embr.202051921

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.
Authors
Muus, C; Luecken, MD; Eraslan, G; Sikkema, L; Waghray, A; Heimberg, G; Kobayashi, Y; Vaishnav, ED; Subramanian, A; Smillie, C; Jagadeesh, KA; Duong, ET; Fiskin, E; Triglia, ET; Ansari, M; Cai, P; Lin, B; Buchanan, J; Chen, S; Shu, J; Haber, AL; Chung, H; Montoro, DT; Adams, T; Aliee, H; Allon, SJ; Andrusivova, Z; Angelidis, I; Ashenberg, O; Bassler, K; Bécavin, C; Benhar, I; Bergenstråhle, J; Bergenstråhle, L; Bolt, L; Braun, E; Bui, LT; Callori, S; Chaffin, M; Chichelnitskiy, E; Chiou, J; Conlon, TM; Cuoco, MS; Cuomo, ASE; Deprez, M; Duclos, G; Fine, D; Fischer, DS; Ghazanfar, S; Gillich, A; Giotti, B; Gould, J; Guo, M; Gutierrez, AJ; Habermann, AC; Harvey, T; He, P; Hou, X; Hu, L; Hu, Y; Jaiswal, A; Ji, L; Jiang, P; Kapellos, TS; Kuo, CS; Larsson, L; Leney-Greene, MA; Lim, K; Litviňuková, M; Ludwig, LS; Lukassen, S; Luo, W; Maatz, H; Madissoon, E; Mamanova, L; Manakongtreecheep, K; Leroy, S; Mayr, CH; Mbano, IM; McAdams, AM; Nabhan, AN; Nyquist, SK; Penland, L; Poirion, OB; Poli, S; Qi, C; Queen, R; Reichart, D; Rosas, I; Schupp, JC; Shea, CV; Shi, X; Sinha, R; Sit, RV; Slowikowski, K; Slyper, M; Smith, NP; Sountoulidis, A; Strunz, M; Sullivan, TB; Sun, D; Talavera-López, C; Tan, P; Tantivit, J; Travaglini, KJ; Tucker, NR; Vernon, KA; Wadsworth, MH; Waldman, J; Wang, X; Xu, K; Yan, W; Zhao, W; Ziegler, CGK; NHLBI LungMap Consortium,; Human Cell Atlas Lung Biological Network,
MLA Citation
Muus, Christoph, et al. “Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.Nat Med, vol. 27, no. 3, Mar. 2021, pp. 546–59. Pubmed, doi:10.1038/s41591-020-01227-z.
URI
https://scholars.duke.edu/individual/pub1475731
PMID
33654293
Source
pubmed
Published In
Nat Med
Volume
27
Published Date
Start Page
546
End Page
559
DOI
10.1038/s41591-020-01227-z

Lung Regeneration: Cells, Models, and Mechanisms.

Lung epithelium, the lining that covers the inner surface of the respiratory tract, is directly exposed to the environment and thus susceptible to airborne toxins, irritants, and pathogen-induced damages. In adult mammalian lungs, epithelial cells are generally quiescent but can respond rapidly to repair of damaged tissues. Evidence from experimental injury models in rodents and human clinical samples has led to the identification of these regenerative cells, as well as pathological metaplastic states specifically associated with different forms of damages. Here, we provide a compendium of cells and cell states that exist during homeostasis in normal lungs and the lineage relationships between them. Additionally, we discuss various experimental injury models currently being used to probe the cellular sources-both resident and recruited-that contribute to repair, regeneration, and remodeling following acute and chronic injuries. Finally, we discuss certain maladaptive regeneration-associated cell states and their role in disease pathogenesis.
Authors
Konkimalla, A; Tata, A; Tata, PR
MLA Citation
Konkimalla, Arvind, et al. “Lung Regeneration: Cells, Models, and Mechanisms.Cold Spring Harb Perspect Biol, Nov. 2021. Pubmed, doi:10.1101/cshperspect.a040873.
URI
https://scholars.duke.edu/individual/pub1500604
PMID
34750172
Source
pubmed
Published In
Cold Spring Harbor Perspectives in Biology
Published Date
DOI
10.1101/cshperspect.a040873

Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF-PU.1-DPP4 Axis.

Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1-remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment-induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis.
Authors
Wang, L; Wang, E; Prado Balcazar, J; Wu, Z; Xiang, K; Wang, Y; Huang, Q; Negrete, M; Chen, K-Y; Li, W; Fu, Y; Dohlman, A; Mines, R; Zhang, L; Kobayashi, Y; Chen, T; Shi, G; Shen, JP; Kopetz, S; Tata, PR; Moreno, V; Gersbach, C; Crawford, G; Hsu, D; Huang, E; Bu, P; Shen, X
MLA Citation
Wang, Lihua, et al. “Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF-PU.1-DPP4 Axis.Adv Sci (Weinh), vol. 8, no. 19, Oct. 2021, p. e2004673. Pubmed, doi:10.1002/advs.202004673.
URI
https://scholars.duke.edu/individual/pub1493278
PMID
34378358
Source
pubmed
Published In
Advanced Science (Weinheim, Baden Wurttemberg, Germany)
Volume
8
Published Date
Start Page
e2004673
DOI
10.1002/advs.202004673

Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair.

Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, we show that proximal tubular (PT) cells develop a molecularly distinct, pro-inflammatory state following injury. While these inflammatory PT cells transiently appear after mild injury and return to their original state without inducing fibrosis, after severe injury they accumulate and contribute to persistent inflammation. This transient inflammatory PT state significantly downregulates glutathione metabolism genes, making the cells vulnerable to ferroptotic stress. Genetic induction of high ferroptotic stress in these cells after mild injury leads to the accumulation of the inflammatory PT cells, enhancing inflammation and fibrosis. Our study broadens the roles of ferroptotic stress from being a trigger of regulated cell death to include the promotion and accumulation of proinflammatory cells that underlie maladaptive repair.
Authors
Ide, S; Kobayashi, Y; Ide, K; Strausser, SA; Abe, K; Herbek, S; O'Brien, LL; Crowley, SD; Barisoni, L; Tata, A; Tata, PR; Souma, T
MLA Citation
Ide, Shintaro, et al. “Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair.Elife, vol. 10, July 2021. Pubmed, doi:10.7554/eLife.68603.
URI
https://scholars.duke.edu/individual/pub1488661
PMID
34279220
Source
pubmed
Published In
Elife
Volume
10
Published Date
DOI
10.7554/eLife.68603

Research Areas:

Organoids
Pulmonary Fibrosis
Regeneration