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

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2011

University of Ulm (Germany)

Grants:

Mapping Epigenetic Memory of Exposure New To Observe (MEMENTO)

Administered By
Biomedical Engineering
Awarded By
Defense Advanced Research Projects Agency
Role
Co Investigator
Start Date
End Date

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
Cell Biology
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

Publications:

COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.

COVID-19, caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple-organ failure1-4, but little is known about its pathophysiology. Here, we generated single-cell atlases of 23 lung, 16 kidney, 16 liver and 19 heart COVID-19 autopsy donor tissue samples, and spatial atlases of 14 lung donors. Integrated computational analysis uncovered substantial remodeling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in COVID-19 donor heart tissue, and mapped cell types and genes implicated with disease severity based on COVID-19 GWAS. Our foundational dataset elucidates the biological impact of severe SARS-CoV-2 infection across the body, a key step towards new treatments.
Authors
Delorey, TM; Ziegler, CGK; Heimberg, G; Normand, R; Yang, Y; Segerstolpe, Å; Abbondanza, D; Fleming, SJ; Subramanian, A; Montoro, DT; Jagadeesh, KA; Dey, KK; Sen, P; Slyper, M; Pita-Juárez, YH; Phillips, D; Biermann, J; Bloom-Ackermann, Z; Barkas, N; Ganna, A; Gomez, J; Melms, JC; Katsyv, I; Normandin, E; Naderi, P; Popov, YV; Raju, SS; Niezen, S; Tsai, LT-Y; Siddle, KJ; Sud, M; Tran, VM; Vellarikkal, SK; Wang, Y; Amir-Zilberstein, L; Atri, DS; Beechem, J; Brook, OR; Chen, J; Divakar, P; Dorceus, P; Engreitz, JM; Essene, A; Fitzgerald, DM; Fropf, R; Gazal, S; Gould, J; Grzyb, J; Harvey, T; Hecht, J; Hether, T; Jané-Valbuena, J; Leney-Greene, M; Ma, H; McCabe, C; McLoughlin, DE; Miller, EM; Muus, C; Niemi, M; Padera, R; Pan, L; Pant, D; Pe'er, C; Pfiffner-Borges, J; Pinto, CJ; Plaisted, J; Reeves, J; Ross, M; Rudy, M; Rueckert, EH; Siciliano, M; Sturm, A; Todres, E; Waghray, A; Warren, S; Zhang, S; Zollinger, DR; Cosimi, L; Gupta, RM; Hacohen, N; Hibshoosh, H; Hide, W; Price, AL; Rajagopal, J; Tata, PR; Riedel, S; Szabo, G; Tickle, TL; Ellinor, PT; Hung, D; Sabeti, PC; Novak, R; Rogers, R; Ingber, DE; Jiang, ZG; Juric, D; Babadi, M; Farhi, SL; Izar, B; Stone, JR; Vlachos, IS; Solomon, IH; Ashenberg, O; Porter, CBM; Li, B; Shalek, AK; Villani, A-C; Rozenblatt-Rosen, O; Regev, A
MLA Citation
Delorey, Toni M., et al. “COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.Nature, Apr. 2021. Pubmed, doi:10.1038/s41586-021-03570-8.
URI
https://scholars.duke.edu/individual/pub1481186
PMID
33915569
Source
pubmed
Published In
Nature
Published Date
DOI
10.1038/s41586-021-03570-8

Versatile, High-Resolution, and Large Field-of-View Single-Molecule Imaging by Oblique Plane Microscopy

Authors
Brown, P; Kruithoff, R; Zhou, L; Kobayashi, Y; Tata, PR; Millet-Sikking, A; York, AG; Dean, KM; Fiolka, RP; Shepherd, DP
MLA Citation
Brown, Peter, et al. “Versatile, High-Resolution, and Large Field-of-View Single-Molecule Imaging by Oblique Plane Microscopy.” Biophysical Journal, vol. 120, no. 3, 2021, pp. 179A-179A.
URI
https://scholars.duke.edu/individual/pub1481025
Source
wos-lite
Published In
Biophysical Journal
Volume
120
Published Date
Start Page
179A
End Page
179A

YAP1/Hippo pathway and SWI/SNF as critical players in squamous cancers and normal development.

Authors
Ellisen, L; Tata, PR; Zhao, R; Rajagopal, J; Saladi, SV
MLA Citation
Ellisen, Leif, et al. “YAP1/Hippo pathway and SWI/SNF as critical players in squamous cancers and normal development.Molecular Cancer Research, vol. 18, no. 8, 2020, pp. 61–61.
URI
https://scholars.duke.edu/individual/pub1457330
Source
wos-lite
Published In
Molecular Cancer Research : Mcr
Volume
18
Published Date
Start Page
61
End Page
61

A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2.

The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellular responses associated with COVID-19 infection, symptoms, and lethality. To address this, we collected tissues from 11 organs during the clinical autopsy of 17 individuals who succumbed to COVID-19, resulting in a tissue bank of approximately 420 specimens. We generated comprehensive cellular maps capturing COVID-19 biology related to patients' demise through single-cell and single-nucleus RNA-Seq of lung, kidney, liver and heart tissues, and further contextualized our findings through spatial RNA profiling of distinct lung regions. We developed a computational framework that incorporates removal of ambient RNA and automated cell type annotation to facilitate comparison with other healthy and diseased tissue atlases. In the lung, we uncovered significantly altered transcriptional programs within the epithelial, immune, and stromal compartments and cell intrinsic changes in multiple cell types relative to lung tissue from healthy controls. We observed evidence of: alveolar type 2 (AT2) differentiation replacing depleted alveolar type 1 (AT1) lung epithelial cells, as previously seen in fibrosis; a concomitant increase in myofibroblasts reflective of defective tissue repair; and, putative TP63 + intrapulmonary basal-like progenitor (IPBLP) cells, similar to cells identified in H1N1 influenza, that may serve as an emergency cellular reserve for severely damaged alveoli. Together, these findings suggest the activation and failure of multiple avenues for regeneration of the epithelium in these terminal lungs. SARS-CoV-2 RNA reads were enriched in lung mononuclear phagocytic cells and endothelial cells, and these cells expressed distinct host response transcriptional programs. We corroborated the compositional and transcriptional changes in lung tissue through spatial analysis of RNA profiles in situ and distinguished unique tissue host responses between regions with and without viral RNA, and in COVID-19 donor tissues relative to healthy lung. Finally, we analyzed genetic regions implicated in COVID-19 GWAS with transcriptomic data to implicate specific cell types and genes associated with disease severity. Overall, our COVID-19 cell atlas is a foundational dataset to better understand the biological impact of SARS-CoV-2 infection across the human body and empowers the identification of new therapeutic interventions and prevention strategies.
Authors
Delorey, TM; Ziegler, CGK; Heimberg, G; Normand, R; Yang, Y; Segerstolpe, A; Abbondanza, D; Fleming, SJ; Subramanian, A; Montoro, DT; Jagadeesh, KA; Dey, KK; Sen, P; Slyper, M; Pita-Juárez, YH; Phillips, D; Bloom-Ackerman, Z; Barkas, N; Ganna, A; Gomez, J; Normandin, E; Naderi, P; Popov, YV; Raju, SS; Niezen, S; Tsai, LT-Y; Siddle, KJ; Sud, M; Tran, VM; Vellarikkal, SK; Amir-Zilberstein, L; Atri, DS; Beechem, J; Brook, OR; Chen, J; Divakar, P; Dorceus, P; Engreitz, JM; Essene, A; Fitzgerald, DM; Fropf, R; Gazal, S; Gould, J; Grzyb, J; Harvey, T; Hecht, J; Hether, T; Jane-Valbuena, J; Leney-Greene, M; Ma, H; McCabe, C; McLoughlin, DE; Miller, EM; Muus, C; Niemi, M; Padera, R; Pan, L; Pant, D; Pe'er, C; Pfiffner-Borges, J; Pinto, CJ; Plaisted, J; Reeves, J; Ross, M; Rudy, M; Rueckert, EH; Siciliano, M; Sturm, A; Todres, E; Waghray, A; Warren, S; Zhang, S; Zollinger, DR; Cosimi, L; Gupta, RM; Hacohen, N; Hide, W; Price, AL; Rajagopal, J; Tata, PR; Riedel, S; Szabo, G; Tickle, TL; Hung, D; Sabeti, PC; Novak, R; Rogers, R; Ingber, DE; Gordon Jiang, Z; Juric, D; Babadi, M; Farhi, SL; Stone, JR; Vlachos, IS; Solomon, IH; Ashenberg, O; Porter, CBM; Li, B; Shalek, AK; Villani, A-C; Rozenblatt-Rosen, O; Regev, A
MLA Citation
Delorey, Toni M., et al. “A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2.Biorxiv, Feb. 2021. Pubmed, doi:10.1101/2021.02.25.430130.
URI
https://scholars.duke.edu/individual/pub1476053
PMID
33655247
Source
pubmed
Published In
Biorxiv
Published Date
DOI
10.1101/2021.02.25.430130

Identification of a Repair-Supportive Mesenchymal Cell Population during Airway Epithelial Regeneration.

Tissue regeneration requires coordinated and dynamic remodeling of stem and progenitor cells and the surrounding niche. Although the plasticity of epithelial cells has been well explored in many tissues, the dynamic changes occurring in niche cells remain elusive. Here, we show that, during lung repair after naphthalene injury, a population of PDGFRα+ cells emerges in the non-cartilaginous conducting airway niche, which is normally populated by airway smooth muscle cells (ASMCs). This cell population, which we term "repair-supportive mesenchymal cells" (RSMCs), is distinct from conventional ASMCs, which have previously been shown to contribute to epithelial repair. Gene expression analysis on sorted lineage-labeled cells shows that RSMCs express low levels of ASMC markers, but high levels of the pro-regenerative marker Fgf10. Organoid co-cultures demonstrate an enhanced ability for RSMCs in supporting club-cell growth. Our study highlights the dynamics of mesenchymal cells in the airway niche and has implications for chronic airway-injury-associated diseases.
Authors
Moiseenko, A; Vazquez-Armendariz, AI; Kheirollahi, V; Chu, X; Tata, A; Rivetti, S; Günther, S; Lebrigand, K; Herold, S; Braun, T; Mari, B; De Langhe, S; Kwapiszewska, G; Günther, A; Chen, C; Seeger, W; Tata, PR; Zhang, J-S; Bellusci, S; El Agha, E
MLA Citation
Moiseenko, Alena, et al. “Identification of a Repair-Supportive Mesenchymal Cell Population during Airway Epithelial Regeneration.Cell Rep, vol. 33, no. 12, Dec. 2020, p. 108549. Pubmed, doi:10.1016/j.celrep.2020.108549.
URI
https://scholars.duke.edu/individual/pub1470181
PMID
33357434
Source
pubmed
Published In
Cell Reports
Volume
33
Published Date
Start Page
108549
DOI
10.1016/j.celrep.2020.108549

Research Areas:

Organoids
Pulmonary Fibrosis
Regeneration