Avinash Waghray
- COVID-19 Clinical Research Studies
- Neonatal Respiratory Health Research
- SARS-CoV-2 and COVID-19 Research
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Extracellular vesicles in disease
- RNA modifications and cancer
- Long-Term Effects of COVID-19
- Congenital Diaphragmatic Hernia Studies
- Renal and related cancers
- RNA Interference and Gene Delivery
- Gene Regulatory Network Analysis
- IL-33, ST2, and ILC Pathways
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Ferroptosis and cancer prognosis
- Pediatric health and respiratory diseases
- Developmental Biology and Gene Regulation
- Microtubule and mitosis dynamics
- Protein Degradation and Inhibitors
- Asthma and respiratory diseases
- Immune cells in cancer
- RNA regulation and disease
Massachusetts General Hospital
2017-2024
Harvard Stem Cell Institute
2018-2024
Broad Institute
2020-2024
Harvard University
2017-2024
Sanofi (United States)
2023
Inflammation Research Foundation
2023
Icahn School of Medicine at Mount Sinai
2010-2020
Tumori Foundation
2020
Dana-Farber Cancer Institute
2020
Massachusetts Institute of Technology
2020
There is pressing urgency to understand the pathogenesis of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme (ACE2), and in concert with host proteases, principally transmembrane serine protease (TMPRSS2), promotes cellular entry. The cell subsets targeted by tissues factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, mouse...
Abstract Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated fresh tumors, single-nucleus (snRNA-Seq) needed profile frozen or hard-to-dissociate tumors. Each requires customization different tissue and types, posing a barrier adoption. Here, we have developed systematic toolbox for profiling clinical samples using scRNA-Seq snRNA-Seq, respectively. We analyzed 216,490 nuclei 40 across 23 specimens spanning...
ABSTRACT The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) associated proteases, transmembrane protease serine (TMPRSS2) Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess cell type-specific RNA expression ACE2 , TMPRSS2 CTSL through integrated...
Mechanisms underlying severe coronavirus disease 2019 (COVID-19) remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune non-immune linked to COVID-19. Deconvolution of our proteome data using published scRNA-seq datasets reveals contributions from circulating tissue cells. Sixteen percent display reduced inflammation yet comparably poor outcomes. Comparison who died severely ill survivors...
Abstract The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune cellular responses associated with COVID-19 infection, symptoms, lethality. To address this, we collected tissues from 11 organs during clinical autopsy of 17 individuals who succumbed COVID-19, a bank approximately 420 specimens. We generated...
Summary COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 patients and 78 symptomatic controls serial timepoints using two complementary approaches, we uncover host immune non-immune not previously linked to this disease. Integration of proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage,...
Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss Tbx3 induces differentiation mouse embryonic cells (mESCs). However, we show that mESCs exist an alternate stable pluripotent state absence Tbx3. In-depth transcriptome analysis this mESC reveals Dppa3 as direct downstream target Also, facilitates cell fate transition from to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation....
Loss-of-function studies are fundamental for dissecting gene function. Yet, methods to rapidly and effectively perturb genes in mammalian cells, particularly stem scarce. Here we present a system simultaneous conditional regulation of two different proteins the same cell. This harnesses plant auxin jasmonate hormone-induced degradation pathways, is deliverable with only lentiviral vectors. It combines RNAi-mediated silencing endogenous expression exogenous whose induced by external ligands...
Analyses of gene expression in single mouse embryonic stem cells (mESCs) cultured serum and LIF revealed the presence two distinct cell subpopulations with individual signatures. Comparisons published data that first subpopulation are phenotypically similar to isolated from inner mass (ICM). In contrast, second appear be more mature. Pluripotency Gene Regulatory Network (PGRN) reconstruction based on single-cell suggested antagonistic roles for Oct4 Nanog maintenance pluripotency states....
Adult stem cells play a crucial role in tissue homeostasis and repair through multiple mechanisms. In addition to being able replace aged or damaged cells, provide signals that contribute the maintenance function of neighboring cells. lung, airway basal also produce cytokines chemokines response inhaled irritants, allergens, pathogens, which affect specific immune cell populations shape nature response. However, direct cell-to-cell signaling contact between has not been demonstrated....
The human airway contains specialized rare epithelial cells whose roles in respiratory disease are not well understood. Ionocytes express the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), while chemosensory tuft asthma-associated alarmins. However, surprisingly, exceedingly few mature have been identified lung cell atlases despite ready identification of ionocytes and neuroendocrine cells. To identify progenitors define their lineage relationship to cells, we generated a deep...
Hematopoietic stem cells (HSCs) exist in a dormant state and progressively lose regenerative potency as they undergo successive divisions. Why this functional decline occurs how information is encoded unclear. To better understand stored, we performed RNA sequencing on HSC populations differing only their divisional history. Comparative analysis revealed that genes upregulated with divisions are enriched for lineage regulated by cell-cycle-associated transcription factors, suggesting...
Abstract Single cell genomics is essential to chart the complex tumor ecosystem. While single RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated fresh tissues, nucleus (snRNA-Seq) needed profile frozen or hard-to-dissociate tumors. Each strategy requires modifications fit unique characteristics of different tissue and types, posing a barrier adoption. Here, we developed systematic toolbox for profiling clinical samples using scRNA-Seq snRNA-Seq, respectively. We tested eight types...