Stanley N. Cohen, MD

Postdoctoral Advisees

Ran Chen, Ning Deng, Sun Young Jeong, Johan Kers, Kwang-sun Kim, Anastasia Levitin, Mikhail Martchenko, Min Song

Web Site Links

• S.N.Cohen Lab Web Site

Industry Relationships

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Research Interests

Certain of our investigations are aimed at elucidating the signals that govern RNA decay. We use E. coli to investigate the mechanism of action of specific ribonucleases and related proteins, and to identify RNA substrate signals that govern stability. We are also interested in the developmental aspects of RNA stability, and study mechanisms that lead to changes in decay during morphological and biochemical differentiation in the developmentally complex bacterial genus, Streptomyces. Recently, we have begun to use a novel approach, random homozygous knockout (RHKO; see below), to identify components of RNA decay pathways in eukaryotic cells.

Our lab has long been interested in the mechanisms that lead to the evolution and dissemination of antibiotic resistance, and currently, we continue to pursue these interests by investigating the biology of linear plasmids of Streptomyces. In particular, we are interested in the mechanisms by which these plasmids interact with chromosomes to acquire and transfer genes, how plasmids evolve and undergo alterations in structure and how their telomeres function to facilitate these events and propagate plasmid DNA. Studies using DNA microarrays are aimed directly at understanding genetic pathways that regulate antibiotic production and resistance.

Some members of our lab use RHKO (random homozygous knockout) and related approaches, together with DNA microarray analysis, to investigate processes that limit the growth of mammalian cells. RHKO, a genetic method we developed to inactivate mammalian cell genes randomly and homozygously, enables the identification of genes whose loss of function leads to altered growth properties. The TSG101 gene, which was the first gene we identified using RHKO, has now been found to affect endocytic processes as well as established pathways that regulate cell division, and remains an important subject of study in our lab.

A small bioinformatics team within our research group has...

Publications

• Identification of cellular genes affecting the infectivity of foot-and-mouth disease virus. Piccone ME, Feng Y, Chang AC, Mosseri R, Lu Q, Kutish GF, Lu Z, Burrage TG, Gooch C, Rock DL, Cohen SN. J Virol. 2009; 83 (13): 6681-8
• Autoregulation of AbsB (RNase III) expression in Streptomyces coelicolor by endoribonucleolytic cleavage of absB operon transcripts. Xu W, Huang J, Cohen SN. J Bacteriol. 2008; 190 (15): 5526-30
• YmdB: a stress-responsive ribonuclease-binding regulator of E. coli RNase III activity. Kim KS, Manasherob R, Cohen SN. Genes Dev. 2008; 22 (24): 3497-508
• Genomic expression profiling of TNF-alpha-treated BDC2.5 diabetogenic CD4+ T cells. Lee LF, Lih CJ, Huang CJ, Cao T, Cohen SN, McDevitt HO. Proc Natl Acad Sci U S A. 2008; 105 (29): 10107-12
• Identification of amino acid residues in the catalytic domain of RNase E essential for survival of Escherichia coli: functional analysis of DNase I subdomain. Shin E, Go H, Yeom JH, Won M, Bae J, Han SH, Han K, Lee Y, Ha NC, Moore CJ, Sohlberg B, Cohen SN, Lee K. Genetics. 2008; 179 (4): 1871-9