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 NYUCD 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.
to truly understand how MAC functions, she explains,its
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 dont 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.
attacks, strokes, and cancer are the focus of Dr. Kinnallys
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.