Christopher Grunseich, M.D.

Christopher Grunseich, M.D., Staff Clinician, NINDS

Christopher Grunseich, M.D.

Staff Clinician
Address
HEREDITARY NEUROLOGICAL DISEASE SECTION, NEUROGENETICS BRANCH

BG 35 RM 2A-1010
35 CONVENT DR
BETHESDA MD 20814

Dr. Chris Grunseich is a Staff Clinician in the Neurogenetics Branch, NINDS. He completed his undergraduate studies at Brown University, and went on to receive his M.D. from SUNY Stony Brook School of Medicine in 2006. While at SUNY Stony Brook he completed an HHMI research fellowship year working in the laboratory of Dr. Gail Mandel. He then completed medical internship at St. Vincent’s Hospital, and his residency training in neurology at Georgetown University. He joined Dr. Kenneth Fischbeck’s research group as a neurogenetics fellow, and has been a Staff Clinician since 2016. He is board certified in Neurology.

His research focuses on clinical studies of patients with motor neuron disease and using patient-derived cell models to better understand the biology of motor neuron diseases.

Dr. Grunseich and his research group are interested in studying genetic forms of motor neuron diseases, developing clinical and molecular markers of disease progression, and performing clinical studies to evaluate candidate therapies in motor neuron disease patients. They have recently performed clinical studies of exercise and an IGF-1 pathway stimulating agent in patients with spinal and bulbar muscular atrophy (SBMA) and have used the MRI measurement of thigh muscle volume to evaluate efficacy.

The group uses patient derived cell models to better understand the biology of motor neuron diseases such as SBMA and inherited forms of ALS. To generate sufficient numbers of cells for their studies, they have developed a system to introduce inducible hNIL transcription factor (NGN2, ISL1, and LHX3) transgene cassettes into the patient- derived stem cells, which facilitates their rapid and efficient differentiation to motor neurons. These cells can then be used to better understand the disease and evaluate candidate therapies.

One of the disruptions in RNA biology that they have characterized in the patient cells is a dysregulation of R-loops. R-loops form as newly transcribed RNA hybridizes to its DNA template to form an RNA-DNA hybrid. In studying amyotrophic lateral sclerosis due to senataxin mutation, ALS4, the group discovered that patients have defects in RNA processing from dysregulation of R-loops. They characterize the distribution of R-loops in differ¬ent cell types and show how the senataxin mutation results in a gain of function in senataxin’s ability to resolve R-loops within patient cells.