The Sherman lab studies mechanisms by which neural progenitor cells and glial cells differentiate in early nervous system development and in demyelinating and neurodegenerative conditions including multiplesclerosis (MS), ischemic and traumatic injury, Alzheimer’s Disease, and age-related cognitive decline. The lab integrates molecular, cellular, physiological, and behavioral approaches in human, non-human primate and rodent models. They focus on the function of the glycosaminoglycan hyaluronan (HA) and its receptor, the transmembrane glycoprotein CD44, in each of these processes. They have characterized drugs that promote remyelination in a novel model of multiple sclerosis in Japanese macaques housed at the ONPRC. These same drugs protect brain vascular endothelial cells from ferroptosis, providing a potential way to limit the progression of vascular dysfunction linked to dementia.

The Sherman lab is also investigating molecular mechanisms by which the SWI/SNF chromatin remodeling complex regulates nervous system development and diseases. We have found that the BRG1 subunit of this complex is critical for early brain and spinal cord development as well as the specification of oligodendrocytes. In addition, we have identified a mechanism by which Schwann cells bearing mutations in the SMARCB1 SWI/SNF subunit, which occur in a large percentage of schwanomatosis patients, secrete factors that induce increased TRPV1 expression by sensory neurons accompanied by increased pain sensitivity. These data were used to support a clinical trial for pain in schwannomatosis patients. We are currently examining how mutations in other genes linked to schwannomatosis impact pain sensitivity.