Vidyadhara D J, MSc, PhD

I am a neurobiologist specializing in Parkinson’s disease and neurodegeneration research, with a background in medical physiology. I am interested in studying the role of presynaptic endolysosomal system in neurodegeneration, particularly in Parkinson’s disease, with a long-term goal of unravelling how genetic and environmental perturbations disrupt presynaptic terminals and their aging, leading to neurodegeneration.

My research background: My journey in neuroscience began during my Master's in Medical Physiology, where I developed a profound interest in the motor system and its disorders, prompting me to pursue a Parkinson's disease (PD) focused PhD. My work revealed mechanisms behind mice strain-dependent susceptibility to parkinsonian toxin MPTP, shedding light on ethnicity-based differences in PD prevalence. Additionally, we pioneered the delineation of age-related glial changes in the human nigra, which significantly contributed to the morphology-based identification of glial cell activation. Collaborations for PD drug development and exposure to patient deep brain stimulation surgeries further solidified my dedication to PD research, a commitment I carried into my postdoc at Yale.

During my postdoc, I specialized in endolysosomal dysfunctions of PD, focusing on auxilin and GBA. I authored a highly cited review on this topic within a year of joining. In a recently published study, we unveiled how auxilin-linked PD involves dopamine transporter and synaptic vesicle sorting defects. While establishing the importance of auxilin and its function of presynaptic endocytosis in PD, this study also contributed a novel auxilin knockout mice model of PD which is now being used for drug testing. In another study, we delved into mechanisms of cognitive dysfunction in PD and dementia with Lewy bodies. We first showed that GBA-SNCA double mutant mice are a good model to study these conditions, and using snRNA-seq and proteomics, we uncovered α-synuclein pathology independent mechanisms for cognitive dysfunction of GBA-linked PD, along with a putative modifier. I was funded as PI/co-PI for both projects, which also brought collaborations resulting in four related research articles.

I have also ardently pursued leadership and mentoring opportunities, gaining experience in independently steering projects, fostering collaborations, and mentoring students. Yale University recognized my undergrad mentorship with an award, while one of my undergrads won Yale Outstanding Student Employee award. I have raised and managed funds as PI, published as the corresponding author, reviewed federal grants, and contributed to several departmental initiatives like Chair search, establishing high-throughput microscopy at Imaging Core, etc. I've been committed to promoting inclusivity in science through diverse teaching programs, neuroscience outreach, diversity initiatives, and as a founding member of the Yale Neuroscience Postdoc Committee. I was chosen as an Associate for the Intersection Science Fellow Symposium (ISFS) 2023, which mentors and spotlights select postdocs across the US for the faculty job market.

My future research: Dopaminergic presynaptic terminals are often the initial sites affected by neurodegeneration in PD. Nevertheless, their remarkable adaptability and dynamic nature within an otherwise post-mitotic soma present a substantial potential for novel PD therapeutics, if we gain an understanding of the factors underlying early presynaptic degeneration. Recent advances in PD genetics and cell biology have spotlighted the putative role played by the presynaptic endolysosomal system in early degeneration, particularly in processes such as presynaptic clathrin-mediated endocytosis and autophagy. My primary objective as a faculty member is to comprehend how dysfunction within the presynaptic endolysosomal system contributes to neurodegenerative mechanisms in PD. I plan to investigate novel PD-related mutations within presynaptic endolysosomal proteins, exploring their interactions with genetic and environmental risk factors, as well as the influence of age. These studies will reveal insights for innovative treatments and biomarker discovery in PD and related neurodegenerative conditions. With my extensive expertise in PD research and specialized training in endolysosomal dysfunctions, I'm well-prepared to take up this exciting and important work.

RESEARCH SUPPORT/GRANTS:
Michael J. Fox Foundation, Target Advancement Program Grant, Aug. 2021 – Sept. 2023
Project: Pathogenic Mechanisms for Auxilin-mediated Parkinson's Disease
Role: Co-Principal Investigator (US$150,000)
U.S. Dept. of Defense, CDMRP Early Investigator Research Award, July 2019 - 21, NCE till 2022
Project: Role of Lipid Dyshomeostasis in Cognitive Dysfunction of Parkinson's Disease
Role: Principal Investigator (US$340,000)
National Institute of Mental Health and Neurosciences (NIMHANS) Fellowship, May 2012 - April 2017
Role: Ph.D. Scholar (INR 1,260,000, covers complete stipend for 5 years)
Indian Council of Medical Research (ICMR), Declined as I received an extension for previous.
Role: Senior Research Fellow (covers two-year PhD stipend)