Purushothama Rao Tata
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View article: Transforming Biological Foundation Model Representations for Out-of-Distribution Data
Transforming Biological Foundation Model Representations for Out-of-Distribution Data Open
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 pr…
View article: Novel Porcine Model Reveals Two Distinct LGR5 Cell Types During Lung Development and Homeostasis.
Novel Porcine Model Reveals Two Distinct LGR5 Cell Types During Lung Development and Homeostasis. Open
Cells expressing LGR5 play a pivotal role in homeostasis, repair, and regeneration in multiple organs including skin and gastrointestinal tract, yet little is known about their role in the lung. Findings from mice, a widely used animal mod…
View article: Distinct dermal fibroblasts direct mechano-chemical signaling to the epidermis during pregnancy
Distinct dermal fibroblasts direct mechano-chemical signaling to the epidermis during pregnancy Open
Dermal fibroblasts alter extracellular matrix (ECM) and tissue mechanics dynamically in wound healing and fibrosis, however, are understudied in healthy skin remodeling across life stages. Here, by conducting spatio-temporal transcriptomic…
View article: Polybacterial intracellular macromolecules shape single-cell inflammatory profiles in upper airway epithelia
Polybacterial intracellular macromolecules shape single-cell inflammatory profiles in upper airway epithelia Open
Mucosal epithelial cells of the upper airways are continuously exposed to microbes throughout life. Specialized niches such as the anterior nares and the tooth are especially susceptible to dysbiosis and chronic inflammatory diseases. Here…
View article: Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis
Ferret model of bleomycin-induced lung injury shares features of human idiopathic pulmonary fibrosis Open
Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with limited therapeutic options. The development of effective therapies has been hindered by the lack of models that recapitulate key features of human disease. Here we re…
View article: Topology-driven discovery of transmembrane protein S-palmitoylation
Topology-driven discovery of transmembrane protein S-palmitoylation Open
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 res…
View article: Modeling functional responses to pollutant exposure using modular hydrogel supported vascularized alveolosphere-on-a-chip
Modeling functional responses to pollutant exposure using modular hydrogel supported vascularized alveolosphere-on-a-chip Open
Alveolospheres derived from AT2 cells in 3D hydrogels enabled the development of a vascularized alveoli-on-chip model, which was applied to study pulmonary responses to chemical exposure.
View article: Influenza B virus infection alters the regenerative potential of murine alveolar type 2 pneumocytes
Influenza B virus infection alters the regenerative potential of murine alveolar type 2 pneumocytes Open
Respiratory epithelial cells can survive direct infection by influenza viruses, and the long-term consequences of that infection have been characterized in a subset of proximal airway cell types. The impact on the cells that survive viral …
View article: Polybacterial Intracellular Macromolecules Shape Single-Cell Epikine Profiles in Upper Airway Mucosa
Polybacterial Intracellular Macromolecules Shape Single-Cell Epikine Profiles in Upper Airway Mucosa Open
The upper airway, particularly the nasal and oral mucosal epithelium, serves as a primary barrier for microbial interactions throughout life. Specialized niches like the anterior nares and the tooth are especially susceptible to dysbiosis …
View article: Topology-Driven Discovery of Transmembrane Protein<i>S</i>-Palmitoylation
Topology-Driven Discovery of Transmembrane Protein<i>S</i>-Palmitoylation Open
Protein S -palmitoylation is a reversible lipophilic posttranslational modification regulating a diverse number of signaling pathways. Within transmembrane proteins (TMPs), S -palmitoylation is implicated in conditions from inflammatory di…
View article: Altered ontogeny and transcriptomic signatures of tissue-resident pulmonary interstitial macrophages ameliorate allergic airway hyperresponsiveness
Altered ontogeny and transcriptomic signatures of tissue-resident pulmonary interstitial macrophages ameliorate allergic airway hyperresponsiveness Open
Introduction Environmental exposures and experimental manipulations can alter the ontogenetic composition of tissue-resident macrophages. However, the impact of these alterations on subsequent immune responses, particularly in allergic air…
View article: Secretory cells dominate airway CFTR expression and function in human airway superficial epithelia
Secretory cells dominate airway CFTR expression and function in human airway superficial epithelia Open
Rationale: Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full characterization of CFTR expression in nor…
View article: SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia
SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia Open
To study viral replicative fitness of SARS-CoV-2 variants of concern in primary human airway cells.
View article: Analysis of Protein Cysteine Acylation Using a Modified Suspension Trap (Acyl-Trap)
Analysis of Protein Cysteine Acylation Using a Modified Suspension Trap (Acyl-Trap) Open
Proteins undergo reversible S -acylation via a thioester linkage in vivo. S -palmitoylation, modification by C16:0 fatty acid, is a common S -acylation that mediates critical protein-membrane and protein-protein interactions. The most wide…
View article: Stem cell migration drives lung repair in living mice
Stem cell migration drives lung repair in living mice Open
View article: Recent advances in lung organoid development and applications in disease modeling
Recent advances in lung organoid development and applications in disease modeling Open
Over the last decade, several organoid models have evolved to acquire increasing cellular, structural, and functional complexity. Advanced lung organoid platforms derived from various sources, including adult, fetal, and induced pluripoten…
View article: Transitional cell states sculpt tissue topology during lung regeneration
Transitional cell states sculpt tissue topology during lung regeneration Open
View article: Host range, transmissibility and antigenicity of a pangolin coronavirus
Host range, transmissibility and antigenicity of a pangolin coronavirus Open
View article: Meta-Analysis of COVID-19 BAL Single-Cell RNA Sequencing Reveals Alveolar Epithelial Transitions and Unique Alveolar Epithelial Cell Fates
Meta-Analysis of COVID-19 BAL Single-Cell RNA Sequencing Reveals Alveolar Epithelial Transitions and Unique Alveolar Epithelial Cell Fates Open
Single-cell RNA sequencing (scRNA-seq) of BAL cells has provided insights into coronavirus disease (COVID-19). However, reports have been limited by small patient cohorts. We performed a meta-analysis of BAL scRNA-seq data from healthy con…
View article: GAA deficiency disrupts distal airway cells in Pompe disease
GAA deficiency disrupts distal airway cells in Pompe disease Open
This research highlights the impact of Pompe disease on distal airway cells. Prior to this work, respiratory insufficiency in Pompe disease was classically attributed to pathology in respiratory muscles and motor neurons. Using the Pompe m…
View article: Efficient Adeno-associated Virus–mediated Transgenesis in Alveolar Stem Cells and Associated Niches
Efficient Adeno-associated Virus–mediated Transgenesis in Alveolar Stem Cells and Associated Niches Open
Targeted delivery of transgenes to tissue-resident stem cells and related niches offers avenues for interrogating pathways and editing endogenous alleles for therapeutic interventions. Here, we survey multiple adeno-associated virus (AAV) …
View article: Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung
Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung Open
Using scRNA-seq and microscopy, we describe a cell that is enriched in the lower airways of the developing human lung and identified by the unique coexpression of SCGB3A2/SFTPB/CFTR . To functionally interrogate these cells, we apply a sin…
View article: An integrated cell atlas of the lung in health and disease
An integrated cell atlas of the lung in health and disease Open
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these lim…
View article: Allergic Asthma Responses Are Dependent on Macrophage Ontogeny
Allergic Asthma Responses Are Dependent on Macrophage Ontogeny Open
The ontogenetic composition of tissue-resident macrophages following injury, environmental exposure, or experimental depletion can be altered upon re-establishment of homeostasis. However, the impact of altered resident macrophage ontogene…
View article: Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis
Novel porcine model reveals two distinct LGR5 cell types during lung development and homeostasis Open
Cells expressing LGR5 play a pivotal role in homeostasis, repair, and regeneration in multiple organs including skin and gastrointestinal tract, yet little is known about their role in the lung. Findings from mice, a widely used animal mod…
View article: Sex differences in resilience to ferroptosis underlie sexual dimorphism in kidney injury and repair
Sex differences in resilience to ferroptosis underlie sexual dimorphism in kidney injury and repair Open
In both humans and mice, repair of acute kidney injury is worse in males than in females. Here, we provide evidence that this sexual dimorphism results from sex differences in ferroptosis, an iron-dependent, lipid-peroxidation-driven regul…
View article: Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication
Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication Open
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who…
View article: A Roadmap for the Human Oral and Craniofacial Cell Atlas
A Roadmap for the Human Oral and Craniofacial Cell Atlas Open
Oral and craniofacial tissues are uniquely adapted for continuous and intricate functioning, including breathing, feeding, and communication. To achieve these vital processes, this complex is supported by incredible tissue diversity, vario…
View article: Coupled myovascular expansion directs cardiac growth and regeneration
Coupled myovascular expansion directs cardiac growth and regeneration Open
Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in…
View article: Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration
Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration Open