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Michael T. McManus, Ph.D.

Michael McManusAssistant Professor Diabetes Center

University of California, San Francisco Diabetes Center
513 Parnassus Ave
HSW 1053A, Box 0534
San Francisco, CA 94143-0534

Tel: (415) 502-2049
Fax: (415) 731-3612

Email: mmcmanus@diabetes.ucsf.edu

The McManus Lab

Michael T. McManus obtained his Ph.D. from the University of Alabama in Birmingham, where he studied RNA editing in the laboratory of Stephen L. Hajduk. He did his postdoctoral training as a Cancer Research Institute fellow, in the laboratory of Nobel Laureate Phillip A. Sharp at the Massachusetts Institute of Technology (MIT), studying the role of RNA-interference pathways in mammals. Last year he was appointed as an Assistant Professor in the University of California San Francisco Diabetes Center, in the Department of Microbiology and Immunology. He has a long-standing interest in post-transcriptional gene regulation and the role of small RNAs in gene expression.

The McManus lab studies biological processes relating to RNA interference pathways, using the mouse as a model. This includes the study of small (18-26 nucleotide) regulatory RNAs of biological significance, such as microRNAs, and the genetic factors involved in small RNA genesis.

In the past few years several groups have published the sequences for over 500 microRNAs from plants to humans and this number is growing. In fact, approximately 1% of all known human genes encode microRNAs, yet we know very little about their function. Our lab is interested in understanding how microRNAs contribute to the specification of cell fate, and how deregulation of microRNAs may contribute to human disease.

We have generated a mouse knockout for the gene called Dicer, which is the catalytic engine of small RNA production in cells. We are using this mouse to explore the role of small RNAs in developmental and immune biology settings. The roles of small RNAs may be much broader than anticipated, thus Dicer may be a ‘master regulator’ in a number of different contexts. Genetic data in C. elegans indicates that Dicer depletion results in loss of the ability to do RNA interference and developmental defects. In S. pombe, knockout of Dicer results in loss of heterochromatic silencing, suggesting a potential role for small RNAs in transcriptional gene silencing. In fact, evidence is accumulating that small RNAs may key mediators in DNA methylation. We believe that the small regulatory RNAs that have discovered are just the ‘tip of the iceberg’ in a set of important biologies that we are far from understanding.

Current projects include the use of RNA expression arrays (both mRNA and microRNA), mouse transgenics (both knock-outs and knock-ins), and biochemical approaches in cell culture aimed at dissecting mechanisms of small RNA biology.