My research program is multi-disciplinary and interfaces basic science with clinical translation. After initial training in Medicinal Chemistry & Pharmacy (PhD, University of Pittsburgh), and Structural Biology (Post-doc, Yale University & HHMI) I started an independent laboratory at New York University Medical Center, where we studied molecular mechanisms underlying the life- and infection-cycles of the cervical cancer-associated papillomaviruses.
Moving to Cincinnati Children’s Hospital in 2002 provided the exciting opportunity to adapt my research program to one that would benefit from the ready access to pediatric clinical programs at Cincinnati Children's. We currently use a combination of animal models, single-cell transcriptomics, mechanistic biochemistry and structure-aided drug design to elucidate mechanisms that promote, and interventions that prevent, the proliferation of cells under conditions of oxidative stress.
Current research in the Hegde Lab focuses on two areas: cancer biology and pulmonary arterial hypertension.
In our cancer projects we work closely with the Sarcoma Program at Cincinnati Children's to develop patient-derived tumor models (patient-derived xenografts PDX and tumor organoids). Hypothesis-based drug-sensitivity studies using these models are leading to novel therapeutic strategies for pediatric sarcomas (for which there has been no advance in treatment since the discovery of chemotherapeutics many decades ago!). We are currently working with our oncology collaborators on the design of an investigator-initiated clinical trial using biopsy-derived biomarkers predictive of response to novel combinations of targeted therapeutics.
In the Pulmonary Arterial Hypertension (PAH) project we are investigating a molecular pathway that contributes to the survival and proliferation of smooth muscle cells in the lungs of Pulmonary Arterial Hypertension patients, leading to occlusion of arterioles, and ultimately contributing to heart failure. We have shown that inhibition of an unusual enzyme, EYA3, has both protective and therapeutic effects in an animal model of Pulmonary Arterial Hypertension. The goal of this project is to test newly developed inhibitors of EYA3 for their effectiveness in reversing Pulmonary Arterial Hypertension.
In addition to research I have been deeply involved in graduate education at Cincinnati Children's. I am a past-director of the Molecular and Developmental Biology graduate program and the founding director of the graduate program in Biomedical Research Technologies.