Hart Lab

In Dr. Hart’s nearly 40-year career as a funded vascular biologist, his interests and focus have evolved from studying basic mechanisms of systemic and pulmonary vascular endothelial and smooth muscle cell dysregulation in vitro to examination of rodent models of disease leveraging approaches that cause targeted gain and loss of gene function in vivo. Most recently, these studies have focused on pulmonary hypertension, an important clinical problem for which new therapeutic approaches are urgently needed. Therapeutic studies in animal models have been employed along with collaborative epidemiological studies to advance the field to define novel insights and therapeutic approaches for pulmonary hypertension. In addition to his clinical and administrative duties, Dr. Hart has enjoyed mentoring early-career trainees in the lab and helping them launch their academic careers.

Dr. Hantelys recently joined the Hart lab and brings her considerable basic science skills to advance several projects. Her primary focus will be studies exploring the role of the outer mitochondrial membrane protein, mitoNEET, in pulmonary vascular cell function. Our previous studies determined that mitoNEET expression is increased in dysfunctional, proliferative pulmonary artery smooth muscle cells from patients and animal models with pulmonary hypertension. MitoNEET regulates mitochondrial iron levels thereby influencing mitochondrial redox balance and mitochondrial function and metabolism. These features play important roles in pulmonary hypertension pathogenesis. Further, thiazolidinedione antidiabetic medications (previously shown to attenuate pulmonary hypertension in animal models) bind directly to this mitochondrial target. Collectively, these observations underlie recently funded studies to explore the role of mitoNEET in pulmonary hypertension pathogenesis and the mechanisms by which pharmacological ligands to this protein favorably impact pulmonary vascular cell function to improve pulmonary hypertension.  

Ms. Murphy is a 40-year Emory University employee and has been the Lab Manager and research technician for Dr. Hart’s lab for nearly 17 years. Her current focus in the lab is studying the role of mitoNEET in pulmonary hypertension. Ms. Murphy is also responsible for performing animal studies in the lab.

Dr. Smith is a VA Health Research Scientist and Assistant Professor of Medicine. He brings his expertise in mitochondrial biology, oxidative stress, and environmental toxicology to the Hart Lab. Through his VA Career Development Award, he is investigating how mitochondrial dysfunction in chronic lung disease-associated pulmonary hypertension (CLD-PH) drives metabolic reprogramming and vascular remodeling in pulmonary artery smooth muscle cells. This project utilizes in vitro smooth muscle cell models isolated from both human subjects and animals with CLD-PH. He aims to identify the specific metabolic enzyme(s) or pathways responsible for driving metabolic reprogramming and to evaluate their potential as therapeutic targets for remediation. A second focus of this project is to assess whether platelets can serve as metabolic biosensors for detecting metabolic reprogramming and mitochondrial dysregulation in humans with CLD-PH. If successful, platelets could provide a less invasive method to assess metabolic health in CLD-PH patients. Dr. Smith also investigates novel molecular mechanisms of mitochondrial dysregulation caused by toxicological agents relevant to military service, such as exposure to perfluorinated chemicals (e.g., PFAS) or inhalation of heavy metals such as cadmium as they relate to disease pathogenesis. As a member of the Clinical Biomarkers Laboratory in the PACCSM Division and the HERCULES Exposome Research Center in the Rollins School of Health at Emory University, Dr. Smith brings expertise with high-resolution metabolomics and exposomics datasets, as well as multi-omic analytic approaches, to understand the molecular mechanisms by which toxicological exposures drive metabolic dysregulation as a driver of disease pathogenesis. Faculty profile: 

Dr. Trammell brings clinical expertise and a translational research focus to the Hart lab, specializing in chronic lung disease-associated pulmonary hypertension (CLD-PH) and its intersections with metabolism. Through his NIH K23 career development award, he is pioneering the use of platelet bioenergetic analysis to understand metabolic dysfunction in CLD-PH patients—a common but understudied form of PH that lacks effective treatments. His research tests the hypothesis that mitochondrial energy metabolism abnormalities are present in CLD-PH and can be targeted therapeutically with agents like pioglitazone. His K23-funded project includes two major studies: 1) a translational study that enrolls participants with CLD-PH and healthy and disease controls to assess platelet mitochondrial function, and 2) a first-in-disease phase 2 crossover trial of pioglitazone in CLD-PH (https://clinicaltrials.gov/study/NCT06336798). Dr. Trammell also utilizes clinical data from the VA and other sources to better understand risk and outcome of PH, often mentoring medical trainees in research projects. Clinically, Dr. Trammell provides specialized care for patients with all forms of PH at The Emory Clinic.