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Ronald Jemmerson, Ph.D.
Professor
Department of Microbiology
Northwestern University, 1978, Ph.D.
jemme001@umn.edu
612-625-1402 office
612-625-7626 lab
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Research Interests:
B cell and antibody recognition of protein antigens; Cytochrome
c and apoptosis
My laboratory participated in the seminal study published in 1996 showing
that cytochrome c (Cyt c) translocates from mitochondria
to the cytoplasm during apoptosis and plays a key role in the activation
of this form of cell death (Cell 86: 147-157). These discoveries
depended on the application of monoclonal antibodies (mAbs) that we had
prepared. One mAb reacted with native Cyt c and was used to deplete
the protein from cytosol, thus showing that Cyt c was critical
in initiating apoptosis in vitro. The other mAb reacted with
the carboxyl terminal peptide of non-native Cyt c and was used
in western blotting to detect translocation of Cyt c to the cytoplasm
in apoptotic cells. We have since employed mAbs reactive with native human
and mouse/rat Cyts c to develop enzyme-linked immunosorbent assays
(ELISAs) for quantifying Cyt c. These assays allowed us to discover
that Cyt c translocates from apoptotic cells as an intact protein
(Cell Death Differ. 9:538-548). Several clinical trials that
have since been reported indicate that serum levels of Cyt c
can detect aberrant apoptosis in vivo, such as in patients who
may develop encephalopathy following influenza virus infection.
In collaboration with the laboratory of Dr. Janet Dubinsky in the Department
of Neuroscience, we have investigated the mechanisms of Cyt c
release from isolated rat brain mitochondria. We have found that, in response
to activated BID, the channel-forming proteins BAK and BAX mediate Cyt
c release without damage to the mitochondrial outer membrane.
In contrast, calcium at high levels, as would occur during stroke, causes
swelling of the mitochondrial matrix and lysis of the outer membrane.
Both mechanisms are likely to be operative during stroke and other neurological
disorders and so we propose that both should be targeted clinically to
try to ameliorate these diseases.
Recently, we discovered that leucine-rich alpha-2-glycoprotein-1 (LRG),
present in serum and expressed by some cells, binds Cyt c. We
hypothesize that LRG is a survival protein that interferes with the apoptotic
function of Cyt c, so we are carrying out experiments to test
this possibility. Serum LRG has been implicated as a biomarker for cancer
and microbial infections. We have developed an ELISA to quantify LRG employing
Cyt c to capture LRG and a mAb specific for LRG to detect the
captured glycoprotein. This assay should be useful clinically to further
assess the value of LRG as a biomarker.
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.
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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 18, 2008
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