About

Purushothama Rao Tata is an Associate Professor of Cell Biology at Duke University and serves as the Director of the Duke Regeneration Center. He is also an Associate Professor in Medicine and a member of the Duke Cancer Institute, with an affiliation to the Duke Regeneration Center. His research focuses on regenerative biology and related biomedical sciences, contributing to the understanding of cellular regeneration processes. He is based at the Duke Department of Biostatistics and Bioinformatics, located at 303 Research Dr, Sands Bldg/Room 451, Durham, NC 27710, and can be contacted via purushothamarao.tata@duke.edu.

Research topics

• Biology
• Pathology
• Immunology
• Medicine
• Virology
• Genetics
• Internal medicine
• Computational biology
• Pharmacology
• Chemistry
• Cell biology
• Cancer research

Selected publications

• New approaches to uncover COPD pathobiology and develop therapies

  JCI Insight · 2026-02-23

  articleOpen access

  Chronic obstructive pulmonary disease (COPD) was the third leading cause of global mortality in 2011 but receives limited attention and research funding. This Review describes the current knowledge on COPD risk factors, including genetic and epigenetic determinants and their interactions with the microbiome and environmental exposures. Preclinical models are being refined and single-cell transcriptomic, metabolomic, and proteomic technologies are being implemented to investigate the molecular mechanisms of disease progression. Patient cohorts to define biomarkers of early disease and the latest approaches to diagnose pre-COPD are essential to accelerate the development of novel and effective therapeutic interventions and translate new findings into clinical trials. This Review is a summary of topics covered by a symposium organized by the COPD-iNET consortium, an international network of researchers who have established a platform that facilitates collaboration of this multidisciplinary group of preclinical, translational, and clinical researchers.

  PublisherOA PDFDOI

• TP53/TAU axis regulates microtubule bundling to control alveolar stem cell–mediated regeneration

  Journal of Clinical Investigation · 2026-02-05 · 1 citations

  articleOpen accessSenior author

  Cells exhibit diverse sizes and shapes, tailored for functional needs of tissues. Lung alveoli are lined by large, extremely thin epithelial alveolar type 1 cells (AT1s). Their characteristic morphology is essential for lung function and must be restored after injury. The mechanisms underlying small, cuboidal alveolar type 2 cell (AT2) differentiation into thin AT1s remain elusive. Here, we demonstrated that AT2s undergo a stepwise morphological transformation characterized by the development of a unique thick microtubule (MT) bundle organization, critical for AT1 morphology. Using AT2 cultures and in vivo genetic loss-of-function models, we found that MT bundling occurred in a transitional cell state during AT2 differentiation and was regulated by the TP53/TAU (encoded by the microtubule-associated protein tau [MAPT] gene) signaling axis. Notably, TAU underwent a linear clustering process, forming beads-on-a-string-like pattern that preceded thick MT bundle formation. Genetic gain or loss of function of TAU in mouse or human models prevented the formation of thick MT bundles, highlighting the critical role of precise TAU levels in generating ultrathin AT1s. This defect was associated with increased tissue fibrosis following bleomycin-induced injury in vivo. GWAS analysis revealed risk variants in the MAPT locus in lung diseases. Moreover, TP53 controlled TAU expression and its loss phenocopied TAU deficiency. This work revealed an unexpected role for TAU in organizing MT bundles during AT2 differentiation.

  PublisherOA PDFDOI

• Stem cell migration drives lung repair in living mice

  Developmental Cell · 2026-02-24

  articleOpen access
  PublisherDOI

• Spatially resolved proteomics identifies dysregulation of signalling pathways in terminal and respiratory bronchioles of patients with mild COPD

  2026-03-19

  article

  <bold>Introduction:</bold> Chronic obstructive pulmonary disease is a major disease burden across the world, and is characterized by chronic inflammation and emphysema. Micro-ct imaging has revealed that a loss of the smallest airways, consisting of the terminal and respiratory bronchioles, are remodeled during the earliest stages of COPD. However, the underlying mechanisms of this remodeling are not well understood. <bold>Methods:</bold> <fig><object-id>erjor;12/suppl_18/PS228/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <bold>Results:</bold> The proteomes of both the respiratory bronchiole and the terminal bronchiole of patients with mild COPD are substantially altered, showing an enrichment of keratinization and interferon signaling in the RB. Cell deconvolutions shows that a loss of TRB-secretory cells in RBs of patients with mild COPD coincided with higher proportions of AT2 cells, which was confirmed by single nuclear RNA sequencing. Lastly, data driven gene program analysis identified several gene programs enriched in TRB-SCs from patients with mild COPD, which were also dysregulated in the proteome. <bold>Conclusion:</bold> Using a data-driven gene program analytical pipeline, we uncovered dysregulation of multiple signaling pathways in the terminal and respiratory bronchioles of patients with mild COPD. These findings provide new insights into the molecular mechanisms underlying small airway loss and may support the identification of novel therapeutic targets for early disease intervention.

  PublisherDOI

• An integrated single-cell and spatial proteotranscriptomics atlas of fibroblast-driven immunoregulation within the human adult oral cavity

  Cell Press Blue · 2026-03-23

  articleOpen access
  PublisherOA PDFDOI

• CFTR-Mediated Ion and Fluid Transport by Primary Ferret AT2 Epithelia

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  article

  Abstract Rationale: Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR channel. While the involvement of CFTR in regulating salt and fluid movement by conducting airway epithelia has been well-studied, its role in alveolar epithelial type II (AT2) cells remains poorly understood. Given that ferrets are excellent models of CF disease, we investigated CFTR-mediated transepithelial ion and fluid transport of ferret primary AT2 epithelia in air-liquid interface (ALI) and organoid cultures. Methods: Primary AT2 cells were isolated from wild-type (WT) and CFTR-G551D/G551D ferret lungs by FACS and propagated in organoid cultures. CFTR-mediated transepithelial chloride transport was assessed in ALI cultures by measuring short-circuit current (Isc), while fluid transport was evaluated using organoid swelling assays. Results: Primary ferret AT2 cells retained their phenotype in proliferative culture conditions as assessed by immunostaining and qRT-PCR for AT2 and AT1 markers (SFTPC, AGER, HOXP1). Following forskolin induction of cAMP to stimulate CFTR, WT AT2 organoid swelled by 18.8 ± 3.8% of their starting volume, while G551D AT2 organoids shrunk in volume by 20.8 ± 5.9% of their initial volumes. These findings suggest that under cAMP stimulatory conditions, CFTR facilitates fluid secretion by AT2 cells and in its absence fluid absorption dominates. In the presence of amiloride and DIDS to inhibit ENaC and non-CFTR anion channels, respectively, IBMX/forskolin induced chloride currents by WT AT2 ALI cultures (ΔIsc 33.57 ± 9.65 µA/cm2), but not G551D cultures (ΔIsc 0.13 ± 0.69 µA/cm2). Conclusion: We demonstrate the ability to propagate ferret AT2 cells and maintain them as undifferentiated epithelia in ALI and organoid cultures. chloride movement by AT2 cells facilitates salt-mediated fluid movement, which counterbalances CFTR-independent fluid absorption. The mechanisms by which these processes interact in native mixed epithelial populations containing both AT2 and AT1 cells remain to be determined. These findings highlight the crucial role of CFTR in sustaining fluid homeostasis in the alveoli.

  PublisherDOI

• Modeling functional responses to pollutant exposure using modular hydrogel supported vascularized alveolosphere-on-a-chip

  Biomaterials Science · 2025-01-01

  articleOpen access

  Alveolar type 2 (AT2) cells play a pivotal role in maintaining lung homeostasis, and the generation of three-dimensional cultures, such as alveolospheres, provides a valuable model for studying lung development, pathologies, and drug responses. Here, we investigate the critical extracellular matrix (ECM) characteristics that influence AT2 alveolosphere formation and growth. By encapsulating AT2 cells in different extracellular matrix-based hydrogels, we identified laminin as a key ECM protein supporting robust alveolosphere formation akin to Matrigel. Our results show that laminin-rich hydrogels support alveolosphere formation across murine and human primary AT2 cells as well as induced human pluripotent stem cell derived AT2 cells (iAT2 cells). Notably, matrix stiffness strongly influenced alveolosphere formation. Hydrogels with a low Young's modulus and high compliance supported a greater number of alveolospheres, exhibiting a broader size distribution and a higher proportion of larger alveolospheres. Moreover, inhibition of matrix degradation and cellular contractility disrupted alveolosphere formation. Leveraging these insights, we developed a multicellular vascularized alveolosphere-on-a-chip model by integrating alveolospheres with endothelial cells and lung fibroblasts within a microfluidic device. Application of this model to assess the inflammatory effects of menthol, a common e-cigarette flavor, demonstrates its utility in evaluating the pulmonary effects of chemical exposures on alveolar cells. Our findings highlight the critical role of matrix physicochemical properties on alveolosphere formation and establish a versatile platform for advancing the study of lung biology, disease mechanisms, and drug discovery.

  PublisherOA PDFDOI

• USHER: Guiding Foundation Model Representations through Distribution Shifts

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-21

  preprintOpen access

  Abstract Foundation models pre-trained on certain biological data modalities exhibit systematic representational biases when encountering out-of-distribution (OOD) data from new assays. The embedding drift largely arises from instrumentation and protocol-related artifacts rather than true biological variation in cell states or tissue morphology. These drifts are distinct from conventional batch effects and cannot be remedied by retraining as sample sizes are often insufficient, and modifying existing embeddings breaks downstream tools that depend on stable representations. We introduce USHER, an adaptable framework to learn simple transforms that return OOD embeddings to a foundation model’s reference space. USHER enables embedding transformation via an expectation maximization-style procedure. Given a reference in-distribution sample, USHER first estimates a Fused Gromov-Wasserstein coupling that aligns unpaired OOD (source) and reference (target) embeddings by minimizing transport distance while preserving local structure. To make optimal transport couplings more useful for down-stream tasks, we introduce the concept of entropic filtering to retain only high-confidence correspondences. In the second step, USHER learns a low-complexity transformation that reliably restores the model’s representation space for OOD data. We demonstrate this learned transformation generalizes to other OOD data from similar experimental conditions. We applied USHER to correct platform-specific biases seen when running scGPT on Xenium transcript counts: USHER maps Xenium embeddings back to the native scRNA-seq representation space, improving cell type clustering and cross-platform integration. Histopathology foundation models trained on H&amp;E images fail on MALDI metabolite-profiled tissue images due to data-acquisition artifacts. USHER corrects these, enabling cell-type classification and protein abundance imputation. USHER offers a generalizable framework to make biological foundation models portable across a rapidly-evolving experimental landscape.

  PublisherDOI

• Polybacterial intracellular macromolecules shape single-cell inflammatory profiles in upper airway epithelia

  UNC Libraries · 2025-12-20

  articleOpen access
  PublisherDOI

• Topology-driven discovery of transmembrane protein S-palmitoylation

  Journal of Biological Chemistry · 2025-02-03 · 3 citations

  articleOpen accessSenior author

  Protein S-palmitoylation is a reversible lipophilic posttranslational modification regulating diverse signaling pathways. Within transmembrane proteins (TMPs), S-palmitoylation is implicated in conditions from inflammatory disorders to respiratory viral infections. Many small-scale experiments have observed S-palmitoylation at juxtamembrane Cys residues. However, most large-scale S-palmitoyl discovery efforts rely on trypsin-based proteomics within which hydrophobic juxtamembrane regions are likely underrepresented. Machine learning-by virtue of its freedom from experimental constraints-is particularly well suited to address this discovery gap surrounding TMP S-palmitoylation. Utilizing a UniProt-derived feature set, a gradient-boosted machine learning tool (TopoPalmTree) was constructed and applied to a holdout dataset of viral S-palmitoylated proteins. Upon application to the mouse TMP proteome, 1591 putative S-palmitoyl sites (i.e. not listed in SwissPalm or UniProt) were identified. Two lung-expressed S-palmitoyl candidates (synaptobrevin Vamp5 and water channel Aquaporin-5) were experimentally assessed, as were three Type I transmembrane proteins (Cadm4, Chodl, and Havcr2). Finally, TopoPalmTree was used for the rational design of an S-palmitoyl site on KDEL-Receptor 2. This readily interpretable model aligns the innumerable small-scale experiments observing juxtamembrane S-palmitoylation into a proteomic tool for TMP S-palmitoyl discovery and design, thus facilitating future investigations of this important modification.

  PublisherDOI

Recent grants

• To define the role of SOX9 and Sox9+ cells in alveolar homeostasis and regeneration

  NIH · $738k · 2017–2019

• Molecular control of a novel transitional cell state in alveolar regeneration

  NIH · $2.7M · 2020–2029

• Mechanisms of submucosal gland cell mediated airway regeneration

  NIH · $2.0M · 2019–2025

• To define the role of SOX9 and Sox9+ cells in alveolar homeostasis and regeneration

  NIH · $273k · 2015–2017

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

  NIH · $432k · 2018–2020

Frequent coauthors

• Jayaraj Rajagopal

  61 shared

• Yoshihiko Kobayashi

  Duke University

  49 shared

• Aleksandra Tata

  37 shared

• Hongmei Mou

  Massachusetts General Hospital

  29 shared

• Preetish Kadur Lakshminarasimha Murthy

  University of Illinois Urbana-Champaign

  27 shared

• R. Thomas Lumbers

  University College London

  21 shared

• Jayaraj Rajagopal

  Bharathidasan University

  19 shared

• Timothy E. Reddy

  Duke University

  16 shared