Global Health Nexus, Summer 2002
Cracking Cancer's Codes
Kathleen Walsh Kinnally, R.N., Ph.D., is Professor of Basic Science and Craniofacial Biology
As an expert in the electrophysiology of mitochondrial membranes, Dr. Kathleen Walsh Kinnally spends her days studying the movement of proteins across membranes, or protein translocation in normal cells and in dying cells. She also studies the cascade of events that occur during apoptosis (cell death). By understanding these events, she explains, we will be able to reveal novel targets for turning the process of cell death on or off, depending on the pathology. For example, with heart attacks and strokes you want to turn the process off to minimize cell death. In cancer, you want to turn the process on, because you want those cells to die.
This is not new territory for Dr. Kinnally, who joined NYU Dentistry almost two years ago as a professor of basic science, bringing with her significant funding from both the National Science Foundation (NSF) and the National Institutes of Health (NIH).
Six years ago, Dr. Kinnally published the first paper that clearly demonstrated that proteins move and change compartments through an ion channel. More recently, she described a new mitochondrial channel, the Mitochondrial Apoptosis-Induced Channel, or MAC, which she calls “a target for chemo and heart attack therapies. It is a novel channel that is only found in dead cells, or dying cells, and is assembled early in the cell death program.”
“In order to truly understand how MAC functions,” she explains,“it’s necessary to put it into a simpler system using proteins called life and death regulators, a family of proteins known as bcl-2, which were originally described in children with leukemia. bcl-2 prevents cell death, and if it is overexpressed, it blocks cells from dying and it blocks MAC from forming. The bcl-2 family of proteins are either pro-apoptotic or anti-apoptotic. They need to be balanced. Overexpressing bcl-2 means that a cell lives when it should die. Overexpressing a protein called Bax means that the cell dies. To understand how bcl-2 and Bax work, we put them in yeast because yeast have almost the same fundamental machinery as a mammalian cell has, but they don’t have the process of apoptosis because they are unicellular. Bax kills yeast, but with bcl-2 and Bax, the yeast live. If you express Bax, you get the Mitochondrial Apoptosis-Induced Channel.” Using a technique called patch clamping, Dr. Kinnally is then able to examine single ion channels.
While heart attacks, strokes, and cancer are the focus of Dr. Kinnally’s investigations, the fruits of her discoveries may also have implications for developing new therapies for a variety of degenerative illnesses. As she says, “Apoptosis is a basic phenomenon that can be attributed to almost any pathology.”