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Hydrogen peroxide in endothelial function and dysfunction
The proposed studies will use new biosensors and novel chemogenetic approaches to identify the molecular mechanisms whereby reactive oxygen species (ROS) regulate nitric oxide (NO...
Predicting and Preventing Ventilator-Induced Lung Injury
Project Summary Acute respiratory distress syndrome (ARDS) is a rapid onset respiratory failure that is caused by factors ranging from pneumonia to sepsis. The impact of ARDS is...
Impact of Circulating Myeloid Cell Clusters on Anti-Tumor Immunity
Durable outcomes in subsets of solid cancer patients treated with immune checkpoint inhibitors (ICI) or adoptive cell transfer (ACT) immunotherapy has driven interest in gaining a...
Neuromodulation of long-term sequelae of ischemic acute kidney injury
Project Summary Acute kidney injury (AKI) is recognized as a major risk for progressive chronic kidney disease (CKD). However, the mechanism by which AKI leads to fibrogenesis an...
Identifying Protein-Protein Network Interactions between COPD Susceptibility Genes
PROJECT SUMMARY Genome-wide association studies (GWAS) of complex diseases like COPD have identified many genomic regions associated with disease, but the molecular mechanisms by...
The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma
PROJECT SUMMARY The incidence of esophageal adenocarcinoma (EAC) has risen 10-fold over the past half century and continues to have a dismal prognosis. Known modifiable risk fact...
Mycobacterial Lung Diseases in Virginia: sequencing and clinical determinants of relapse and outcome
PROJECT SUMMARY / ABSTRACT Nontuberculous mycobacterial lung diseases, primarily due to M. avium complex (MAC), is an increasing clinical problem nationwide and now overtakes dom...
Molecular mechanisms and functions of global chromatin control
Project Summary/Abstract The long term goal of the proposed study is to determine, at the molecular level, mechanisms and functions of chromatin regulation at a global level. Chr...
Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infection
PROJECT SUMMARY: Zika virus (ZIKV) is a teratogenic human pathogen that causes congenital eye and brain diseases. Affected babies exhibit vision impairment and associated ocular p...
Dendritic Mechanisms Underlying Behaviorally-Relevant Activity in a Descending Auditory Pathway
Project Summary/Abstract Active listening is central to auditory cognition, supporting critical functions such as stream segregation, linguistic analysis and perceptual learning....
Dynamics of calcium signals control neurotransmitter release in retinal ribbon synapses
Retinal bipolar cells are the first 'projection neurons' of the vertebrate visual system and transmit all of the information needed for vision. Bipolar cells can signal change in...
Control of calcium flux and mitochondrial fission by the Charcot Marie Tooth disease protein Mfn2.
Project summary Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy resulting from demyelination and axon degeneration. Many cases of axon degeneration are ca...
Modeling myelodysplasia
PROJECT SUMMARY Myelodysplastic Syndromes (MDS) are a cancer of the hematopoietic stem cell (HSC) on the rise in the aging population and cancer survivors. The only curative trea...
The role of mitochondria in hematopoietic stem cell self-renewal
Abstract Hematopoietic stem cells (HSC) sustain the production of all blood and immune cells throughout life by differentiating into all blood lineages and regenerate long-lived...
Diffuse optical spectroscopies to assess cerebral hemodynamics in pediatric sickle cell disease
Project Summary Silent cerebral infarction is a serious consequence of sickle cell disease (SCD), affecting ~40% of patients by age 15. Although these injuries accumulate occultl...
Eradication of Escaped Variant Tumor Cells for Cancer Immunotherapy
Project Summary Recently, we discovered that adoptive transfer of CD39KO tumor-specific (mixed CD4+ and CD8+) T cells, resulted in long-term survival of mice bearing large establ...
Stromal senescence in lethal prostate cancer: a novel target for prognosis and therapy
Our overarching hypothesis is that senescent stromal fibroblasts, especially if they elicit an inflammatory response, promote progression to lethal disease in men with prostate ca...
Mechanisms of Sex Determination in Zebrafish
The Problem: Differences in (or Disorders of) Sex Development (DSD) are complex medical issues that involve multiple interacting cell types and organ systems. DSDs impact disease...
Role of mitophagy in age-related respiratory and vascular diseases
PROJECT SUMMARY/ABSTRACT The overarching theme of my research program is to understand how innate immunity enhances age- associated cardiovascular and pulmonary diseases. As a ph...
Epigenomics of asthma risk factors and clinical subtypes in minority children
PROJECT SUMMARY Asthma is the most common chronic disorder of children, with an estimated 300 million cases worldwide and with significant increases in incidence since the early...