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Michael Koob, Ph.D. Assistant Professor, Department of Neurology E-mail: koobx001@umn.edu

Research Interests:

We have identified trinucleotide mutations that cause two forms of spinocerebellar ataxia, SCA7 and SCA8, and are focusing our efforts on characterizing at the molecular level the genes involved in SCA8. The CTG trinucleotide expansion mutation that causes SCA8 is in an antisense RNA that appears to be involved in the regulation of another transcript that encodes a brain-specific protein we have called Kelch-like 1 (KLHL1). We are studying the interaction of these two RNAs as well as the molecular properties and functions of the KLHL1 protein using mouse, zebrafish, Drosophila, and tissue culture models.

Our results to date indicate that KLHL1 is an actin-organizing molecule that is specifically expressed in a variety of neurons in the brain, and is localized to the cell body and dendrites of these cells. We have recently found that mice in which we over-express the endogenous KLHL1-antisense RNA develop a pronounced hyperactive, circling phenotype indicative of defects in neurons in the basal ganglia. We are currently characterizing both this model and a mouse model in which we have deleted the KLHL1 sense and antisense genes.

Selected Publications:

Yoon YG, Haug CL, Koob MD. Interspecies mitochondrial fusion between mouse and human mitochondria is rapid and efficient. Mitochondrion. 2007 May;7(3):223-9.

Aromolaran KA, Benzow KA, Koob MD, Piedras-Rentería ES. The Kelch-like protein 1 modulates P/Q-type calcium current density. Neuroscience. 2007 Mar 30;145(3):841-50.

He Y, Zu T, Benzow KA, Orr HT, Clark HB, Koob MD. Targeted deletion of a single Sca8 ataxia locus allele in mice causes abnormal gait, progressive loss of motor coordination, and Purkinje cell dendritic deficits. J Neurosci. 2006 Sep 27;26(39):9975-82.

Yoon YG, Koob MD. Transformation of isolated mammalian mitochondria by bacterial conjugation. Nucleic Acids Res. 2005 Sep 12;33(16):e139.

Mutsuddi M, Marshall CM, Benzow KA, Koob MD, Rebay I. The spinocerebellar ataxia 8 noncoding RNA causes neurodegeneration and associates with staufen in Drosophila. Curr Biol. 2004 Feb 17;14(4):302-8.