Basic science is a key part of the PMDC's work. Through its Pilot Grants Program, the Center gives seed funding to VCU investigators who study the pathogenesis behind Parkinson's disease, related movement disorders and overlapping neurodegenerative conditions. These projects come from across the university, including the Departments of Neurology, Biology, Surgery, and Anatomy & Neurobiology/Neuroscience & Anatomy, the School of Pharmacy, the School of Nursing and Massey Cancer Center. Many are collaborations across departments, and several are led by postdoctoral fellows and MD/PhD trainees working with faculty mentors. The research uses cell lines, C. elegans, and rat and mouse models. Methods include CRISPR gene activation, lipidomics and phosphoproteomics, in vivo calcium imaging, optogenetics, and whole-brain light-sheet microscopy.
The projects share one goal: to find the earliest changes that make neurons vulnerable, and to turn them into targets for treatment. Some study the genetic and molecular roots of Parkinson's. Others ask how environmental exposures and brain injury set neurodegeneration in motion. Others look at how failing brain circuits might be rescued. Pilot funding lets these teams collect the preliminary data they need to compete for larger federal and foundation grants.
Basic Research Themes
- Genetic and molecular drivers of Parkinson's disease. Drs. Santiago Lima and Jason Newton are examining how loss of GBA (glucocerebrosidase), the most common genetic risk factor for PD, changes membrane lipids and Trk receptor signaling in ways that cause α-synuclein to build up. Dr. Rohil Hameed, mentored by Dr. Alaattin Kaya, is screening conserved essential genes in a humanized C. elegans PD model to find new neuroprotective targets.
- Environmental toxins and epigenetics. Drs. Laxmikant Deshpande and Joseph McClay use rat models to study how pesticide exposure affects the brain. They have looked at rotenone-induced parkinsonism and chlorpyrifos-linked memory loss, focusing on epigenetic changes such as histone acetylation. Their newest project studies how disruption of the blood vessels supplying the brain (ANGPT2-related) makes dopamine-producing neurons more vulnerable.
- Brain injury as a path to neurodegeneration. Dr. Kirsty Dixon's lab studies how traumatic brain injury, ApoE4 and TNF-driven inflammation combine to damage synapses and promote Alzheimer's-type pathology. MD/PhD trainee Chelsie Poffenberger is extending this work to the retina as a possible early window onto disease.
- Circuits, memory and restoring function. Dr. Aaron Barbour and colleagues use activity-dependent labeling and optogenetics in an early-stage (prodromal) Alzheimer's model to test whether overactive neurons cause memory failure and whether that damage can be reversed. Dr. Megan Rajagopal's work studies whether brain stimulation can promote new neuron growth with lasting benefit in dementia models.