The goal of Dr. Karch’s research is to understand the molecular and cellular mechanisms underlying tauopathies. As a graduate student, she studied the basic mechanisms by which mutant SOD1 protein aggregates in cell and mouse models of amyotrophic lateral sclerosis. As a postdoctoral fellow, Dr. Karch expanded her research to define and characterize the mechanisms by which cells release tau and how genetic variability associated with tauopathies influence tau release. He team is currently investigating the mechanisms underlying regional vulnerability to tau aggregation, the role that tau spreading plays in this vulnerability, and how we can therapeutically target these mechanisms in Alzheimer’s disease and other tauopathies.
To do this, her lab studies tau expression/splicing, tau aggregation, and protein clearance machinery in traditional immortalized cell models and in human induced pluripotent stem cells (iPSCs), which capture the genetic and regulatory complexities of the human MAPT gene and allows for the investigation of several neuronal subtypes from the same individual. Her lab a variety of iPSC lines that are genetically predisposed to developing tauopathies: Alzheimer’s disease-associated mutations in PSEN1 and PSEN2; frontotemporal dementia-associated mutations in MAPT, and genes that increase risk for tauopathies. Defining the molecular and cellular mechanisms underlying tauopathies will improve our understanding of how genetic predisposition to tauopathies influences tau biology and will inform novel avenues for therapeutic intervention.