Postdoctoral fellow positions and graduate student rotation projects are available. Contact Dr. Yongchao Ma.
Regulation of Neural Stem Cell Development and Neurodegeneration by RNA Methylation
RNA methylation on N6-adenosine (m6A) has emerged as a crucial regulator of RNA function and metabolism, directly influencing protein expression and biological functions. We recently identified novel m6A RNA readers that interpret RNA methylation to control diverse aspects of RNA biology, including its localization, degradation and translation. We are investigating how RNA methylation regulates fundamental processes in neural development and degeneration, such as neurogenesis, neural stem cell differentiation, and neuroinflammation. We also explore its role in the pathogenesis of autism, ALS and other neurological disorders.
To uncover these molecular mechanisms, we employ a combination of genetic, biochemical and cell biological approaches, using genetically modified mice and human induced pluripotent stem (iPS) cells. We employ next generation sequencing and data analysis to map RNA methylation sites, and we develop novel RNA methylation-based therapeutics through high-throughput drug screening.
Regulation of Mitochondrial Function in Motor Neuron Degeneration
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, affects one in every eight thousand live births, while amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is the most common motor neuron disease in adults. Both conditions are characterized by the selective degeneration of spinal motor neurons. Our group focuses on understanding the mechanisms that regulate motor neuron development and function, as well as the specific vulnerability of motor neurons in SMA and ALS. To address these questions, we perform single-cell RNA sequencing and signaling pathway analysis, using SMA and ALS mouse models along with stem cell-derived neurons. A key focus of our research is the non-canonical role of mitochondria as signaling hubs, regulating epigenetic and metabolic changes that contribute to neurodegeneration in SMA and ALS.
Aging and Mitochondrial Oxidant Defense in Dopaminergic Neuron Degeneration of Parkinson’s Disease
Dopaminergic neurons in the ventral midbrain control movement, emotional behavior and reward mechanisms. Dysfunction of these neurons is implicated in Parkinson’s disease (PD), drug addiction, depression and schizophrenia. Our group studies the genetic and epigenetic mechanisms regulating dopaminergic neuron functions in disease and aging conditions. We are particularly interested in how aging and impaired mitochondrial oxidative defense contribute to the selective degeneration of dopaminergic neurons in PD through transcriptional and epigenetic changes. For these studies, we use mouse models, cultured neurons, and iPS cells to explore the underlying molecular mechanisms.