Kevin Struhl, PhD
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Eukaryotic Transcriptional Regulation
Investigate basic mechanisms of gene regulation in yeast; Employ mammalian cell models of tumorigenesis to elucidate genetic changes that underlie cancer development and progression
Early-stage studies designed to identify novel protein targets involved in tumorigenesis, and to discern key signaling reactions that lead to altered transcriptional regulation in cancer cells; identify approaches to inhibiting transcription in the fungal strain Candida albicans.
Dr. Struhl’s lab is applying its wealth of experience in transcriptional regulation to studies focusing on the molecular mechanics underlying the transition of a normal cell to a malignant cell. These studies should uncover new molecular targets amenable to drug development. In addition to revealing new insights into the tumorigenic process, Dr. Struhl’s extensive experience and expertise in transcriptional regulation is a valuable asset that companies would benefit from.
On a separate front, the lab is exploring new approaches for combating fungal infections such as C. albicans, a yeast-like organism, which can cause a variety of opportunistic infections, particularly in immunocompromised patients. The lab is interested in applying their extensive knowledge of transcriptional regulation in yeast to search for novel inhibitors of transcription in this organism, capitalizing on the unique features of transcription in C. albicans as compared to other eukaryotic organisms.
Current Research Interests
Dr. Struhl is:
- Continuing his longstanding investigations into the molecular mechanisms of eukaryotic transcriptional regulation, employing yeast as a model system. The lab also has a major focus in cancer biology. Mammalian cell models have been setup that recapitulate the tumorigenic process, with the goal of identifying genes participating in the transformation of normal cells to a transformed state, as well as elucidate regulatory mechanisms that control the changes in expression of these genes during the progression to a malignant cell type.
- Exploring the biochemical and molecular underpinning of transcription and gene expression, employing a variety of advanced technologies
- Studying aberrant transcriptional regulation that drives cancer progression; these studies employ different mammalian cell models along with techniques such as ChIP and genomic screens
Dr. Struhl is considered one of the foremost experts in eukaryotic transcriptional regulation. His lab has studied the myriad of proteins that bind to and modulate DNA-directed RNA synthesis. Mechanisms of eukaryotic transcription are conserved throughout evolution, and the lab has focused on yeast and mammalian cells as model systems to piece apart the activities of nucleic acid-binding proteins, protein complexes, and chromatin that serve to titrate the levels of RNA synthesis in response to different environmental cues. Recent published work has focused on transcriptional aspects related to p63, a homolog of the tumor suppressor p53, and the Swi/Snf protein complex that affects chromatin structure. In addition, Dr. Struhl has authored commentaries pertaining to fidelity of transcription initiation and the biochemical aspects that drive the progression from initiation to elongation of transcription. Studies on p63 revealed mechanisms by which this transcription factor mediates effects on gene expression. Employing a global genomics approach, a specific DNA motif was deduced, and found to be present in a small number of genomic sites that typically possess binding domains for other nucleic acid binding proteins. Data pertaining to the relationship between p63 binding to DNA and transcriptional effects, as well as to previously unidentified target genes was also presented. Dr. Struhl has also played a major role in the production of the widely read laboratory manual, Current Protocols in Molecular Biology, as a member of the editorial board and as a contributor.