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Andrej Rotter

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Professor and Vice Chair for Education

Department of Pharmacology

rotter.1@osu.edu

Education

BS, 1974, University College London, UK
PhD, 1978, National Institute for Medical Research, Mill Hill, UK
Postdoctoral Training, 1978-80, National Institutes of Health, Bethesda, MD

Research Interests

The long term interest of my laboratory centers the molecular analysis of gene expression in signal transduction, cell adhesion and cell recognition pathways fo the cerebellum. Aging-related impairment of motor coordination and balance may result from alterations in specific cerebellar molecules. We have used Serial Analysis of Gene Expression (SAGE) to assess aging-related changes in the cerebellum of adult and aged mice. Combined unique tags for each group revealed 325 differentially expressed genes. Four additional tests (mixed effect model, t-test, Wilcoxon rank-sum and z-test) were used to reduce the likelihood of false positives. Twenty-nine genes were found to be differentially expressed by at least two of the four tests. Several of these coded for key eznymes in the glycerophospholipid metabolic network. Notably, each of the four statistical tests indicated that the expression of a single gene, Agps, decreased in the aged cerebellum. P-chance analysis detected increased expression of two additional members of the glycerophospholipid pathway. Pla2g4b, (phospholipase A2, group IVB) and Gpam (glycerol-3-phosphate acetyltransferase). Our data suggest that functional decrements during senescence may result, at least in part, from a cascade of biochemical events leading to defective myelination and impaired conduction in cerebellar neurons.

Of additional interest in this laboratory is a novel receptor protein tyrosine phosphatase (RPTPr/PTPRT) that is expressed predominantly in the CNS and delineates a unique anterior-posterior boundary in the developing cerebellum. PTPRT is the fourth, and final, member of the receptor protein tyrosine phosphatase (RPTP) R2B family. Each member of this small group of phosphatases has adhesive properties that occur through homophilic interactions and appear to be unique to vertebrate species. In addition to their well-known role in protein dephosphorylation, R2B proteins have been implicated in cell-cell and cell-matrix interactions, neurite extension and axon guidance. Recently, PTPRT was identified as a putative tumor suppressor in lung, colorectal and gastric tumors. We have cloned the human and mouse genes and have used computational gene finding programs to define functional sites that encode elements of R2B gene structure, regulation and transcription. Comparisons with homology domains in a number of databases were used to make functional assignments and to predict the putative 3-D structure of the active phosphatase domain. Alignments of orthologous sequences from a variety of different species utilizing several phylogenetic reconstruction algorithms were used as the basis for phylogenetic analysis and comparative genomics.

Publications

Popesco MC, Lin S, Wang Z, Ma ZJ, Friedman L, Frostholm A, Rotter A (2008) Serial analysis of gene expression profiles of adult and aged mouse cerebellum. Neurobiology of Aging 774-788.

Besco JA, Hooft van Huijsduijnen R, Frostholm A, Rotter A (2007) Intracellular substrates of Receptor Protein Tyrosine Phosphatase Rho (RPTPr/PTPT). Molec Brain Res 1116:50-57.

Wang Z, Lin S, Popesco M, Rotter A (2007) Modeling and analysis of multi-library, multi-group SAGE data with application to a study of mouse cerebellum. Biometrics 63:777-786.

Besco J, Popesco M, Frostholm A, Burghes AHM, Rotter A (2001) Genomic organization of the human receptor protein tyrosine phosphatase rho (RPTPr) gene. BMC Genomics 2:1.

Besco J, Popesco MC, Davuluri RV, Frostholm A, Rotter A (2004) Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phospahtases (PTPk, m, r and PCP-2). BMC Genomics 5:114.

Popesco MC, Frostholm A, Rejniak K, Rotter A (2004) Digital transcriptome analysis in the aging cerebellum. Annals New York Acad Sci V 1019:1-6.​​​​​​