Kevin Gills, Ph.D.
Research Interests
My main area of interest is understanding the
final steps of cell secretion and the modulation
of these steps by protein kinases. We are presently using multiple biophysical
approaches to assay dynamic aspects of
secretion from individual adrenal chromaffin cells. We have found that activation of protein kinase C (PKC)
enhances depolarization-induced exocytosis many fold while actually decreasing
the calcium current which triggers release. Using several different protocols, we
have shown that PKC enhances secretion by increasing the size of the "readily
releasable pool" of secretory granules. On the other hand, our experiments with
caged Ca2+ show that PKC does not shift the Ca2+-sensitivity of the final step in
secretion (see figure below). Since protein kinases play a central role in
regulating both secretion of hormones and release of neurotransmitter at
synapses, the results of our research have an impact on understanding such
diverse phenomena as the "fight or flight" response and the formation of
short-term memory.
In the future, we plan on further characterizing the kinetic steps modulated by
protein kinases. For example, does PKC increase the size of the readily releasable
pool by increasing the "filling" rate or does it stabilize vesicles in the"readily-releasable" state? We also plan to examine the targets of kinase action
at the molecular level.
Our research also has a strong engineering component with particular emphasis
on developing or refining electrical and optical techniques for studying secretion.
Techniques in use in the lab include patch-clamp electro- physiology with
membrane capacitance measurements as an assay of exocytosis/ endocytosis,
amperometric detection of catecholamine secretion with carbon fiber electrodes,
photometric measurement of membrane turnover and intracellular Ca2+
concentration with indicator dyes, and photo- release of intracellular Ca2+ from
caged compounds.
Professional Background
- Received D.Sc. in Electrical Engineering with certificate in Biomedical
Engineering, Washington University, St. Louis
- Postdoctoral training in the Department of Membrane Biophysics,
Max-Planck Institute for Biophysical Chemistry, Goettingen, Germany
- Joined Department in 1996 with joint appointment in Electrical Engineering
- Member of the Biophysical Society
Selected Publications
- Misler, S., L.C. Falke, K. Gillis and M. McDaniels. A metabolite regulated
potassium channel in dispersed rat pancreatic B cells. Proc. Natl. Acad. Sci.
83:7719-7723, 1986.
- Gillis K., W. Gee, A. Hammoud, M. McDaniel, L. Falke and S. Misler. Effects
of sulfonamides on a metabolite-regulated, ATP-sensitive K+ channel in
pancreatic B cells. Am. J. Physiol. 26:C1119-C1127, 1989.
- Gillis, KD and S. Misler. Single cell assay of exo- cytosis from pancreatic
islet B cells. Pfluegers Arch., 420:121-123, 1992.
- Gillis KD and S Misler. Enhancers of cytosolic cAMP augment
depolarization-induced exocytosis from pancreatic B-cells: Evidence for
effects distal to Ca2+ entry. Pfluegers Arch. 424:195-197, 1993.
- Gillis, K.D. Techniques for membrane capaci- tance measurements. In,
Single Channel Recording, 2nd Edition. Edited by B. Sakmann and E. Neher,
Plenum Press, New York, NY, 1995.
- Gillis, K.D., R. Moessner and E. Neher. Protein kinase C enhances exocytosis
from chromaffin cells by increasing the size of the readily-releasable pool of
secretary granules. Neuron 16:1209-1220, 1996.
Methodologies/Techniques
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