Spring 2005 Table of Contents
     
Grants and Philanthropy
NIH Awards NYUCD an Additional $1.4 Million
Grant to Study Inner Workings of Cell Death
 

Dr. Kathleen Kinnally (foreground), Professor of Basic Science and Craniofacial Biology, viewing a cell death simulation with two research associates, Dr. Sergey Grigoriev and Dr. Ana Paul N. Newton.


Time-lapse view of neural cells disintegrating, showing cells before being injected with cytochrome c (image with arrows), which sets off cell death, and after. Within 90 minutes (image at bottom right), the cells shrink, their nuclei condense, and their membranes blister.

Five years after she received a $1.1 million NIH grant, which led to the discovery of a key early stage of apoptosis (cell death), Dr. Kathleen Kinnally has received a new four-year, $1.38 million NIH award to continue her effort to identify proteins that may modulate the severity of heart attacks, strokes, cancer, and other illnesses by turning the cell death program on or off.

With the help of the first grant, Dr. Kinnally discovered that cytochrome c -- a protein that powers cell respiration -- sets off the cell's destruction when it exits the mitochondrion through a pore she named the mitochondrial apoptosis-induced channel (MAC). A protein known as BAX paves the way by punching holes in the membrane. But another protein, Bcl-2, can block the pore's formation and prolong cell life beyond its normal span. Mutated cells that don't die contribute to cancer formation.

These findings were significant because they suggested that treatments could be developed to alter the course of cell death even before it begins. Preventing cell death may decrease the severity of heart attacks and strokes, while initiating cell death can block cancer. Dr. Kinnally has already identified several medications which appear to target cell death's earliest stage, such as Dibucaine, a local anesthetic that rapidly blocks MAC.

But questions remain about how this and other medications interact with the proteins that spawn cell death from deep inside the thick mitochondrial membrane. With her new grant, Dr. Kinnally will investigate whether there may be additional steps involved in opening and closing the mitochondrial apoptosis-induced channel. She will seek to establish which other apoptosis proteins may lurk in the mitochondrial membrane, and how they might be brought under control by medications. To ascertain how these proteins influence MAC, she will use a technique known as patch clamping that detects the electrical currents passing through the channel (high voltage currents signify that the protein is opening the channel; low voltage currents indicate a closing).

Understanding cell death is particularly relevant to oral health, since certain conditions, such as gingival enlargement, may result when cell death and proliferation are out of balance. Oral cancer is another disease in which cell death plays a key role.