Transgenics Section

Huaibin Cai , Ph.D., Chief

Our research focuses on elucidating the circuit- and cell-type–specific mechanisms that drive age-related neurodegenerative disorders, with a primary focus on Parkinson’s disease (PD). PD is a rapidly growing neurodegenerative condition that disproportionately affects older adults and manifests not only with progressive motor impairments but also with debilitating non-motor symptoms — such as depression, chronic pain, cognitive decline, and dementia — that remain inadequately treated.

Leveraging an extensive portfolio of genetically engineered mouse models of PD and related disorders (Lin et al., 2009; Parisiadou et al., 2014; Wu et al., 2019), our work integrates molecular, cellular, synaptic, and systems-level approaches to determine how disease- and age-associated molecular pathologies disrupt neuronal activity in vivo and give rise to behavioral dysfunction. Using state-of-the-art in vivo recording and imaging technologies, including genetically encoded indicators, fiber photometry, and miniscope imaging, we directly measure neurotransmitter dynamics and neuronal firing in defined midbrain dopaminergic and striatal neuron subtypes during behavior across the lifespan (Liu et al., 2022; Dong et al., 2025; Hawes et al., 2025).

By linking age- and disease-related circuit dysfunction to specific motor and non-motor phenotypes, and enabling causal testing through targeted optogenetic and chemogenetic manipulations (Dong et al., 2026), our research provides critical mechanistic insights and therapeutic entry points aligned with NIA priorities to improve health, function, and quality of life in aging populations.