J. Kevin Foskett, PhD

Description of Research Expertise

Research Interests
Ion channels, calcium signaling, cystic fibrosis, Alzheimer's Disease.

Key Words: signal transduction, genetic disease, ion channel, calcium, cystic fibrosis, electrophysiology, Alzheimer's.

Description of Research
Our laboratory is most broadly interested in the molecular biology and physiological mechanisms of solute transport and intracellular signaling, and the roles of these processes in disease. Specifically, we are working in two distinct research areas:

First, we study the molecular physiology of intracellular calcium (Ca2+) release ion channels, esp. the inositol trisphosphate receptor. Calcium release from intracellular storage compartments is a ubiquitous cell signaling mechanism that regulates processes as diverse as fertilization, gene transcription, secretion and learning and memory. The calcium signaling system is amazingly complex in both time and space. A major problem in understanding how this signaling system works is that the release channel is located inside cells. We have developed novel approaches to overcome this limitation. We employ a variety of biophysical, molecular and biochemical approaches to study the molecular physiology of the inositol trisphosphate receptor calcium channel, ranging from single molecule studies to optical imaging of calcium signals in individual cells.

Of primary interest now is the role of this channel and Ca2+ signaling in programmed cell death, autophagy and Alzheimer's Disease.

The second focus of the lab is the disease cystic fibrosis. CF is the most common lethal recessive genetic disease. It is caused by mutations in the gene product, named CFTR, which is a chloride ion channel that is expressed in the tissues affected in the disease, including lungs, pancreas, reproductive tract and intestines. Our focus now is on the submucosal glands in the lung,which play important roles in lung homeostasis and innate immune defense, and where CFTR is expressed at high levels. These glands are complex and composed of many cells types. We are using a combination of single cell gene expression profiling, electrophysiology and optical imaging to identify the function and role of each cell type in the gland.

The techniques we employ span the spectrum from biophysical to molecular, reflecting our approach as cell physiologists. Biochemical and molecular tools are used within the context of physiological measurement. Our goal is to understand how molecular behavior results in complex cell physiological processes, including those involved in signal transduction and epithelial and nerve cell functions. We employ:

- electrophysiology, including nuclear envelope patch clamping, two-electrode voltage clamp of oocytes and single channel recording from mammalian cells;
- confocal imaging microscopy of single living cells
- microinjection
- yeast 2-hybrid system
- expression studies
- molecular biology
- biochemistry

Rotation Projects for 2009-2010
Determined on an individual basis, depending on students' interests, current state of research interests/priorities in the lab, and discussions with the student. Some interests as of April, 2009:

Inositol trisphosphate receptor calcium channels.
Some specific areas of interest now:
• Role of InsP3R in programmed cell death, autophagy and Alzheimer's Disease. Could learn: PCR, blot hybridization, binding assays, recombinant DNA techniques, patch clamp electrophysiology, two-electrode voltage clamp, expression, recombinant DNA techniques, single organnelar imaging, mouse physiology, metabolic assays.

• Structure/function of IP3R. Will learn: patch clamp electrophysiology, two-electrode voltage clamp, expression, recombinant DNA techniques.

A novel Ca2+ channel linked to late-onset Alzheimer's Disease.
• Will learn molecular biology, Ca2+ indicator dye fluorescence imaging, patch clamp and two-electrode voltage clamping..

Cystic fibrosis.
Some specific areas of interest now:
• Cellular physiology of lung submucosal glands in pigs and humans. Involves live celloptical imaging and electrophysiology, and single cell gne expression profiling.


Lab personnel:
Dr. Daniel Mak, PhD (Research Investigator)
Dr. King Ho Cheung, PhD (Postdoctoral Fellow)
Rob Lee (Postdoctoral Fellow)
Adam Siebert (CAMB Graduate Student)
Dustin Shilling (Neuroscience Graduate Student)
Marioly Muller (Univ Santiago Master's Degree Student)
Cesar Cardenas (Postdoctoral Fellow)
Lijuan Mei (Research Specialist)
Horia Vais (Research Specialist)
Jun Yang (Research Specialist)
Christie Gutierrez (Undergrad researcher)