Michael R. Nichols
Dr.
Nichols received his B.S. degree from Lindenwood College and
Ph.D. from Purdue University. Prior to joining the UM-St. Louis
faculty in Fall 2004, he completed a postdoctoral fellowship
at the Mayo Clinic in Jacksonville, FL.
nicholsmic@umsl.edu
Office: B319
Phone: (314) 516-7345
Fax: (314) 516-5342
Photo Gallery
Research Interests
Protein assembly or aggregation is widely recognized as a significant contributing factor to a number of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, and others. Remarkably, the proteins or peptides implicated in these diseases, while possessing different amino acid sequences, all self-assemble to form similar fibrillar structures termed amyloid. One such peptide is amyloid-β (Aβ), a 40-42-residue peptide and the primary component of the senile plaques found in AD brains. The leading hypothesis in AD research maintains that accumulation of aggregated Aβ is the primary cause of the disease.
One research area in my laboratory involves mechanistic studies of Aβ aggregation. Objectives include isolation and characterization of aggregation intermediates and investigation of conditions that influence aggregation.These studies utilize an array of biophysical techniques to probe mechanistic and structural questions.The other major research thrust in my laboratory addresses the question of how Aβ aggregates are detrimental to cells.One hypothesis is induction of a sustained inflammatory response causing the release of harmful cytokines such as tumor necrosis factor-α.We are studying these effects in monocyte/macrophage cells and smooth muscle cells with the goal of understanding the cause of the inflammatory response, how it relates to cell toxicity, and identification of novel ways to regulate cytokine release.
Selected Publications
“Toll-like receptors 2 and 4 mediate Aβ(1-42) activation of the innate immune response in a human monocytic cell line”. M. L. D. Udan, D. Ajit, N. R. Crouse, and M .R. Nichols, J Neurochem, 2008, 104, 524
“Amyloid-β aggregates formed at nonpolar interfaces differ from amyloid-ß protofibrils produced in aqueous buffers”. M. R. Nichols, M. A. Moss, D. K. Reed, J. H. Hoh, and T .L. Rosenberry, Microsc Res Tech, 2005, 67, 164
“Amyloid-ß protofibrils differ from amyloid-β aggregates induced in dilute hexafluoroisopropanol in stability and morphology”. M. R. Nichols, M. A. Moss, D. K. Reed, S. Cratic-McDaniel, J. H. Hoh, and T .L. Rosenberry, J Biol Chem, 2005, 280, 2471
"Nordihydroguaiaretic
acid does not disaggregate β-amyloid(1-40) protofibrils
but does inhibit growth arising from direct protofibril association".M. A.
Moss, N. H. Varvel, M. R. Nichols, D. K. Reed, J. H. Hoh, and
T. L. Rosenberry, Mol Pharmacol, 2004,
"Growth
of β-amyloid(1-40) protofibrils by monomer elongation
and lateral association.Characterization of distinct products
by light scattering and atomic force microscopy". M. R. Nichols,
M. A. Moss, D. K. Reed, W. L. Lin, R. Mukhopadhyay, J. H. Hoh,
and T. L. Rosenberry, Biochemistry, 2002, 41, 6115
"Tyrosine-kinase independent inhibition of cAMP phosphodiesterase by genistein and tyrphostin 51". M. R. Nichols, and B. H. Morimoto, Arch Biochem Biophys, 1999, 366, 244