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:

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.
  • 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