Aditya Bade, PhD, assistant professor in the UNMC Department of Pharmacology and Experimental Neuroscience, recently received a five-year, $2.86 million grant to study effects of HIV-1 medicines on neurodevelopment during pregnancy.
The grant, from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH/NICHD), is Dr. Bade’s first R01 grant.
Dr. Bade, a UNMC graduate, has been on faculty for two years, making this a relatively early-career R01 approval; according to NIH statistics, Dr. Bade is a decade younger than the national mean age for researchers to achieve their first NIH R01 or equivalent award.
Dr. Bade drew from results he had acquired from studying the effects of antiretrovirals on the fetal neurodevelopment through his initial R21 grant that he received in 2021 from NIH/NICHD.
Including the R21 support, Dr. Bade will be continuously supported by NIH/NICHD for 10 years at the end of the R01 funding.
“As a former a graduate student at UNMC, it’s exciting to think that my research will bring educational and training opportunities to other graduate students and early-stage investigators at UNMC,” Dr. Bade said.
Howard Gendelman, MD, chair of pharmacology and experimental neuroscience and one of Dr. Bade’s former mentors, called it “simply remarkable to see the amazing rapid trajectory in research discovery made by Dr. Bade and in such short order. Here the mentee becomes the mentor and a collaborator becomes a principal scientist.
“What is so remarkable is Dr. Bade’s ability to take what he learned as a trainee then forge it into a unique research program that is of immediate international interest and doing so without missing a beat,” Dr. Gendelman said. “We are all proud of what he has become, and the listed grant is only the beginning of his upward trajectory.”
The preliminary work from previously NIH/NICHD supported research led to the new grant, which will allow Dr. Bade and his team to identify underlying mechanisms of commonly used antiretroviral drugs (ARVs)-associated adverse neurodevelopmental outcomes, as well as develop intervention strategies to maximize the safety and therapeutic efficacy of these ARVs during pregnancy.
Dr. Bade said he was excited about the project, which is ramping up now.
“This is area that is completely unexplored,” he said. “Not many labs are focused on looking at how these antiretrovirals might affect fetal development. It’s quite complex.”
Dr. Bade was the first researcher to report that, in an animal model, a first-line antiretroviral drug called dolutegravir reaches fetal brain during pregnancy and inhibits activity of matrix metalloproteinases (MMPs) proteins.
“Such drug-induced secondary action can affect neurodevelopmental process,” he said. His new research will further assess how inhibition of MMPs can adversely affect developmental neuronal processes during pre- and postnatal development and how that may be linked to neurobehavioral outcomes.
“We will use long-acting formulations as potential delivery means to limit the drug exposure to fetal brain during pregnancy to hopefully improve neurodevelopmental outcomes,” he said. “Once successfully completed, we hope such platforms can be extended to other ARVs to improve safety during pregnancy. Perhaps the platforms can be employed on other medications utilized during pregnancy as well.”
Adam Cassidy, PhD, of the Mayo Clinic Division of Neurological Disorders Departments of Psychiatry and Psychology & Pediatric and Adolescent Medicine, spoke to the potential of Dr. Bade’s research.
“Dolutegravir (DTG) is taken by millions of people worldwide, including as first-line treatment for women who are living with HIV and who are pregnant or of childbearing age,” Dr. Cassidy said. “Despite its widespread usage, we know very little about the impact of in utero exposure to DTG on the fetal brain and subsequent neurodevelopment. Dr. Bade’s study represents an important step toward addressing this knowledge gap and I am very excited and eager to work with him as he launches this exciting project.”
While the majority of the research work will be completed in research animal models at UNMC, Dr. Bade will collaborate with Dr. Cassidy’s ongoing clinical study in Botswana for cross-validation of the scientific findings of neurological outcomes and biomarker discovery.
Dr. Bade said: “My ultimate goal is that my research will contribute to improving the health outcomes of fetus and mother following ARV exposures during gestation and enhance the safety and therapeutic efficacy of widely utilized antiretroviral drugs during pregnancy.”