Dr. Cohen's laboratory investigations are aimed at elucidating the signals that govern RNA decay. They use E. coli to investigate the mechanism of action of specific ribonucleases, related proteins, small non-coding RNAs, and to identify cellular events and proteins that regulate the actions of these molecules. They 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.

Their lab has long been interested in the mechanisms that lead to the evolution and dissemination of antibiotic resistance, and currently, they continue to pursue these interests by investigating the biology underlying the ability of bacteria to adapt non-mutationally to antibiotic exposure and other environmental stresses.

Some members of their lab use gene inactivation methods plus phenotypic selection approaches to investigate processes that perturb the biology of mammalian cells. One of these inactivation methods, RHKO (random homozygous knockout), enables the identification of cellular genes whose function is exploited by pathogenic microbes. They investigate the effects of genetic variation in these host genes on host sensitivity to pathogens and toxins. A small bioinformatics team within their research group has developed and implemented a novel system of computer programs (Genetic Analysis By Rules Incorporating Expert Logic; GABRIEL) that uses expert knowledge and statistical algorithms used for analysis of genetic data.

A recent area of investigation is the study of mechanisms that selectively enable transcription through expanded trinucleotide repeats (TNCs) of mammalian genomes and the actions of aggregated proteins generated by such repeats. TNCs have a causal role in a variety of degenerative neurological diseases.