November 03, 2020

Precision Genomics Collaboratory Announces COVID-19 Early Career Investigator Pilot Grant Awards

Stephanie Langel, Matthew McCravy, Grace Lee

Congratulations to the winners of the Precision Genomics Collaboratory Pilot Grants: Stephanie Langel, Ph.D., Matthew McCravy, M.D., and Grace Lee, M.D.

The Duke University School of Medicine Precision Genomics Collaboratory offered pilot grant funding for early career investigators interested in COVID-19 research that broadly involves genomics/’omics. The goal of these pilot grants is to support innovative pilot studies on COVID-19 related to these efforts, to generate data to fuel future grant submissions. 

To be considered for a pilot grant, applicants needed to be assistant professors, instructors, or currently in training (i.e. graduate students, postdoctoral fellows, clinical fellows). We awarded $15,000 grants to three projects.

Congratulations to the Awardees!

Awardee: Stephanie Langel, Ph.D | Postdoctoral Scholar, Duke Human Vaccine Institute (DHVI), Dept. of Pediatrics
Mentor: Maria Blasi, Ph.D. | DHVI, Dept. of Medicine
Collaborator: Scott Palmer, M.D. | Dept of Medicine

Over 200,000 people have died in the U.S. from COVID-19, mostly older Americans and those with preexisting conditions. However, acute SARS-CoV-2 infections in children are mostly mild, with low hospitalization rates and few deaths, a pattern that also emerged in previous coronavirus outbreaks. Recent reports demonstrate that asymptomatic children have similar or higher SARS-CoV-2 RNA levels in nasopharyngeal swabs compared to infected adults, which suggests that the distinct pathogenesis of SARS-CoV-2 infection in children and adults is not driven by the virus but by differences in age-related host factors. Understanding the disease mitigating host factors of airway epithelial cells in children and adults will advance our knowledge on the cellular responses that are critical for protecting against severe COVID-19. This project will use single cell RNA-sequencing technology to define host cellular factors in airway epithelium that mediate differential SARS-CoV-2 responses in infants and adults.

Awardee: Matthew McCravy, M.D. | Dept. of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Mentors: Loretta G. Que, M.D., | Dept. of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Jennifer L. Ingram, Ph.D. | Dept. of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine

Using data from the Duke Health Pathology Biorepository, we will develop a cohort of clinically available data and specimens from obese patients admitted with COVID-19 to assess for metabolic syndrome, use blood samples to genotype patients for single nucleotide polymorphisms in genes associated with abnormal lipid metabolism and increased oxidative stress, and determine significant associations between these polymorphisms and/or metabolic syndrome with use of non-invasive ventilation, mechanical ventilation or tracheostomy in obese patients with COVID-19 pneumonia.

Using that same cohort, we will also obtain clinically available markers of systemic inflammation, assay blood samples for tumor necrosis factor alpha (TNF-α), leptin, adiponectin and glutathione to glutathione disulfide ratio (GSH/GSSG), and quantify the association between these polymorphisms, metabolic syndrome, obesity, and systemic inflammation.

Awardee: Grace Lee, M.D. | Assistant Professor, Dept. of Medicine, Division of Hematology

We will isolate neutrophils from subjects who had asymptomatic/mild cases of COVID-19 who didn’t require hospitalization and have recovered and from subject who had severe cases of COVID-19 that required mechanical ventilation and/or developed thrombosis. We will determine if differences in neutrophil reactivity correlate with COVID-19 severity and characterize those differences. We will use RNA sequencing to identify differences in neutrophil gene expression between the two cohorts. Based on our lab’s preliminary work, our initial focus will be on genes that encode receptors and proteins in signal transduction pathways. We will also examine genes which regulate inflammatory cytokines and proteins involved in the defense response; cell-fate following phagocytosis; gene transcription, translation and DNA binding; ion channels and calcium flux; and neutrophil structure/cytoskeleton, as these have been found to be differentially expressed after activation by various receptor agonists or bacteria.

via Duke Med School Blog