The Katz Lab in the Department of Pathology was recently awarded a National Institutes of Health grant to study the role of a protein called BOK in cell death of neurons.
The approximately $2 million NIH RF1 grant, funded by the National Institute of Neurological Disorders and Stroke (NINDS), is for a multi-year project entitled, “Cell Death Regulation by Pro-Apoptotic BOK in Tauopathies.”
The lab, which studies cell death with the goal of selectively controlling the cell death machinery for therapeutic benefit, will use the grant to study diseases due to aberrant expression of tau, known as tauopathies. Tau is a protein found in neurons that helps maintain their structure and function, but when tau is damaged and clumps together, it can cause neurodegenerative diseases, like Alzheimer’s and frontotemporal dementia.
“Proteins in the BCL-2 family are well known to regulate cell death,” said Samuel Katz, MD, PhD, Associate Professor of Pathology and Principal Investigator of the Katz Lab. “BOK is a poorly understood BCL-2 family member that we have found kills cells in response to the same types of stress that occur when there is too much tau. This grant will allow us to study if BOK is responsible for the death of neurons in tauopathies and discover potential ways to prevent that.”
Dr. Katz has several Yale collaborators, including Pallavi Gopal, MD, Associate Professor of Pathology, Stephania Libreros, PhD, Assistant Professor of Pathology, and Jaime Grutzendler, MD, the Dr. Harry M. Zimmerman and Dr. Nicholas and Viola Spinelli Professor of Neurology and Neuroscience.
The study uses mouse models of tauopathy to determine how BOK regulates cell death due to aberrant Tau in neurons. Dr. Grutzendler’s team has devised a technique to image neurons in a living mouse, stimulate cell death at a single-cell level and measure whether they stay alive or die as they are being treated.