 |
Ronald Jemmerson, Ph.D.
Professor
Department of Microbiology
Northwestern University, 1978, Ph.D.
jemme001@umn.edu
612-625-1402 office
612-625-7626 lab
|
Research Interests:
Antigen-Antibody Interactions; Apoptosis
My laboratory contributed to the seminal study showing that cytochrome
c (Cyt c) translocates from mitochondria to the cytoplasm
during apoptosis and plays a key role in the activation of programmed
cell death (Cell 86:147-157, 1996). Later we and others found
that Cyt c is released from apoptotic cells as an intact protein
(Cell Death Differ. 9:538-548, 2002). Cyt c is now being
employed clinically as a biomarker for aberrant apoptosis as occurs, for
example, in patients who may develop encephalopathy following influenza
virus infection.
While developing an immunoassay to detect Cyt c in serum we discovered
that leucine-rich alpha-2-glycoprotein-1 (LRG) binds Cyt c and
inhibits its detection in an antibody-based assay (Apoptosis
11:1121-1129, 2006). LRG has been implicated as a serum biomarker for
cancer and microbial infections and a urinary biomarker for juvenile appendicitis.
However, its function is unknown. We have shown that LRG binds Cyt c
in a manner similar to that of the protein Apaf-1 that initiates the intrinsic
pathway of apoptosis (C. Thompson, A. Kelekar, and R. Jemmerson, Keystone
Symposium on Apoptosis, Abstract 217, 2007) and proposed that LRG may
be a survival factor that competes with Apaf-1 for binding Cyt c
in the cytoplasm of certain cells. This possibility is currently being
investigated. We have also developed an enzyme-linked immunosorbent assay
for LRG that may be useful clinically (J. Immunol. Methods 336:22-29,
2008).
In related studies, we have collaborated with Dr. Janet Dubinsky, Department
of Neuroscience to understand the mechanisms of Cyt c release
from mitochondria using the rat brain as a model (Antioxid. Redox
Signal. 7:1158-1172, 2005). There are at least two different mechanisms
that appear to be involved. In response to certain types of stress Cyt
c is released without damage to the mitochondrial outer membrane
and in response to high calcium levels, as occurs during stroke, the mitochondrial
matrix swells causing lysis of the outer membrane. Therefore, we propose
that both mechanisms should be targeted to lessen the consequences of
stroke and neurological disorders.
Selected Recent Publications:
- Weivoda, S., Andersen, J. D., Skogen, A., Schlievert, P. M., Fontana,
D., Schacker, T., Tuite, P., Dubinsky, J. M., and Jemmerson, R. 2008.
ELISA for human serum leucine-rich alpha-2-glycoprotein-1 employing
cytochrome c as the capture ligand. J.
Immunol. Methods.
336:22-29.
- Cummings, C., Walder, J., Treeful, A., and Jemmerson, R. 2006. Serum
leucine-rich alpha-2-glycoprotein-1 binds cytochrome c and
inhibits antibody detection of this apoptotic marker in enzyme-linked
immunosorbent assay. Apoptosis
11:1121-1129.
- Jemmerson, R., Dubinsky, J. M., and Brustovetsky, N. 2005. Cytochrome
c release from CNS mitochondria and potential for clinical intervention
in apoptosis-mediated CNS diseases. Antioxid.
Redox Signal. 7:1158-1172.
-
Brustovetsky, T., Antonsson, B., Jemmerson, R., Dubinsky, J. M.,
and Brustovetsky, N. 2005. Activation of calcium-independent phospholipase
A2 (iPLA2) in brain mitochondria and release of apoptogenic factors
by BAX and truncated BID. J.
Neurochem. 94:980-994.
- Brustovetsky, N., Dubinsky, J. M., Antonsson, B., and Jemmerson, R.
2003. Two pathways for tBID-induced cytochrome c release from
rat brain mitochondria: BAK- versus BAX-dependence. J.
Neurochem. 84:196-207.
- Jemmerson, R. 2002.The molecular basis for affinity maturation in
the antibody response to a protein antigen, cytochrome c. Recent.
Res. Devel. Immunology 4:13-25.
- Brustovetsky, N., Brustovetsky, T., Jemmerson, R. and Dubinsky, J.
M. 2002. Calcium-induced cytochrome c release from CNS mitochondria
is associated with the permeability transition and rupture of the outer
membrane. J.
Neurochem. 80:207-218.
Last modified on: August 11, 2009
|
