Eva Otoupalova, MD

My deep interest in pulmonary research started shortly after completing medical school, when I was fortunate to do an internship in the laboratory of Dr. Thannickal at the University of Alabama at Birmingham (UAB). During my internship, I learned about the clinical aspects and poor prognosis of Idiopathic Pulmonary Fibrosis, as well as basic methods of laboratory research. I contributed to a project on how CCN1, a matricellular protein, mediates fibroblast senescence through NOX-4 expression and production of reactive oxygen species, and thus drives progression of Idiopathic Pulmonary Fibrosis. After residency, I returned to UAB as an Assistant Professor of Internal Medicine, and I joined a study in Dr. Thannickal’s laboratory investigating the role of extracellular vesicles (EVs) in Idiopathic Pulmonary Fibrosis. I designed and conducted experiments, analyzed data and set research directions. I found that fibronectin on the surface of EVs mediates an invasive, pro-fibrotic phenotype in lung fibroblasts. The research laid groundwork for future studies looking at the role of EVs in fibrosis and was published as a first-author original investigation in American Journal of Respiratory Cell and Molecular Biology. 

While I loved the creativity and freedom of research, I found myself constantly wondering how I could translate the scientific findings into tangible patient outcomes. Thus, I was inspired to pursue a fellowship in Pulmonary and Critical Care at the University of Virginia (UVA). I joined the laboratory of Dr. Jeffrey Sturek, with the goal of expanding my knowledge in the immunology of interstitial lung diseases (ILD). I developed a project looking at the role of B1 cells and natural antibodies (NAbs) in a cohort of patients with fibrotic ILD, and I found that natural IgA against oxidized lipids is associated with severe ILD. During the COVID-19 pandemic, I applied my clinical experiences to my research when I collaborated on a project investigating the role of B1 cells and NAbs in patients with COVID-19. We found that total and anti-ACE-2 specific IgM levels in patients with COVID-19 correlate with protection from severe disease, and we identified a candidate B-cell cluster associated with high anti-ACE-2 IgM and less severe disease. The findings have been presented at the 2023 ATS Conference and two manuscripts describing my research findings are in preparation for submission.

While my background has previously been in ILD, the COVID-19 pandemic made me realize that I want to focus my career and research skills on addressing other ongoing global health emergencies. I got first interested in tuberculosis (TB) research when I was invited to collaborate on an editorial describing current challenges in diagnostics of childhood tuberculosis. I subsequently developed a collaboration between my primary mentor Dr. Jeffrey Sturek and Dr. Scott Heysell, an accomplished scientist in the area of tuberculosis and TB-sepsis. Our current project investigates the role of B cell responses in TB-sepsis. The project is utilizing samples and infrastructure of the ATLAS trial (clinicaltrials.gov NCT04618198), a randomized multicenter trial evaluating empiric early anti-TB therapy versus standard antibiotic therapy in patients with HIV admitted with suspected sepsis in Tanzania and Uganda. Two additional manuscripts describing our findings are in preparation. 

For the past year, I have been fortunate to continue my research at the Sturek Lab as a post-doctoral fellow under the KUH Ignite National Institute of Health Grant (1U2CDK129500-01 and 1TL1DK132771-01). I also worked as an attending at the UVA Intensive Care Unit during this time. The additional time allowed me to familiarize myself more closely with high dimensional immunophenotyping methods and other immunological methods, conclude my projects focusing on ILD and Covid-19 and the role of natural antibodies, and collect preliminary data for a project investigating the role of humoral immunity in severe forms of TB. I also utilized this time to plan my transition to a faculty position at Tulane University School of Medicine, assemble a mentorship team and develop current proposal evaluating sex-driven differences in immune responses to TB.