Robert M. Klein, PhD
Vice Chancellor for Academic Affairs
Professor of Anatomy & Cell Biology
Ph.D.: 1974, New York University
Postdoctoral: Marquette University
Inflammation is a response to injury that allows the tissues and organs of the body to heal in an organized manner. That process of repair is orchestrated by small proteins, which function as intercellular signals, called cytokines. Cytokines may act in a beneficial way to augment cell survival and normal function or through detrimental mechanisms leading to programmed cell death (known as apoptosis). One class of cytokines is known as the chemokines. The name is derived from a contraction of chemoattractant and cytokine. Chemokines signal specific cells to migrate to the site of inflammation. In peripheral systems, the key cells that are attracted during inflammation are neutrophils and monocyte-derived macrophages. In the CNS, the response is almost entirely monocyte-derived with microglia, the macrophages of the brain, playing a critical role.
Inflammation is no longer considered as a totally beneficial process. While inflammation is a helpful mechanism for the body to mount a defense to destroy viruses and bacteria, inflammation can harm the very tissues it is meant to heal. We are focusing on inflammation as an underlying mechanism across the lifespan from perinatal development to repair in adult brain to aging and aging-related diseases.
We use several different systems to study inflammation and the role of microglia in the response to injury:
- We are studying the effects of maternal infection on fetal brain development. We have determined that there is up-regulation of cytokine and chemokine genes and down-regulation of genes required for the normal differentiation of neurons and wiring of connections. There is also increased activation of microglia in the fetal brain following maternal infection that appears to be correlated with enhanced cytokine/chemokine expression.
- We use a model of cortical injury to study the role of chemokines in the survival of neurons in the process of retrograde neuronal degeneration. In that study, we use genetic/molecular approaches to dissect the mechanisms that allow microglia to influence the balance between cell survival and death in the thalamus following injury to the cortex.
- We are studying the increased microglial activation and increased cytokine/ chemokine gene expression found in the normal aging brain and the effects of dietary manipulations on the aging process.
All of these studies focus on microglia and cytokines/chemokines as well as their role in influencing normal neuronal function, differentiation, and aging.
- Hausmann, E., Berman, N.E.J., Meara, J.B., Liu, W-L., Wood, G.W. and Klein, R.M. Selective chemokine mRNA expression following brain injury. Brain Res., 788: 49-59, 1998
- Muessel, M.J., Berman, NE.J. and Klein, R.M. Expression of monocyte chemoattractant protein-1 in the thalamus precedes retrograde degeneration. Brain Res. 870:211-221, 2000.
- Felzien,L.K., McDonald,J.T., Gleason, S.M., Berman, N.E.J. Klein, R.M. Increased chemokine gene expression during aging in the murine brain. Brain Res. 890: 137-146, 2001.
- McKenzie, J.C., Juan, Y-W., Thomas, C.R., Cothran, L.N., Searson-Norris, L., Berman, N.E.J. and Klein, R.M. Natriuretic Peptide-Like immunoreactivity in astrocytes and neurons of human cerebella. J. Histochem Cytochem. 49: 1453-1467, 2001.
- Choudhuri R., Welch, K.M.A., Cui, L., Bowyer, S., Klein, R.M. and Berman, N.E.J. Cortical spreading depression and gene regulation: Relevance to migraine. Ann. Neurol. 51: 499-506, 2002.
- Gattone, V.H. II, Ricker, J.L., Trambaugh, C., and Klein, R.M. Multiorgan mRNA misexpression in murine autosomal recessive polycystic kidney disease. In press, Kidney International.
- Muessel, M.J., Klein, R.M., Wilson, A.M., and Berman, N.E.J. Ablation of the chemokine monocyte chemoattractant protein-1 delays retrograde neuronal degeneration, attenuates microglial activation, and alters expression of cell death molecules. In press, Molecul. Brain Res.
Aug 30, 2016