Robert P Fisher, MD, PhD
- PROFESSOR | Oncological Sciences
- PROFESSOR | Pharmacological Sciences
Robert Fisher, MD, PhD, is Professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai and a member of The Tisch Cancer Institute. Prior to joining Mount Sinai in 2009, Dr. Fisher was with the Molecular Biology Program at Sloan-Kettering Institute and Cornell University Graduate School of Medical Sciences.
Dr. Fisher has more than 25 years of experience studying the central roles of cyclin-dependent kinases (CDKs) in regulating cell division and gene expression. His laboratory has developed powerful chemical-genetic techniques to identify new components, regulators and targets of the CDK network, and has used these tools to define molecular mechanisms coordinating cell division and transcription that had escaped prior detection by standard procedures. Dr. Fisher and his research team are currently developing novel applications of chemical genetics to illuminate new pathways and mechanisms. His most recent R35 grant from the National Institutes of Health supports research on CDK control of cell-division and transcription cycles.
Dr. Fisher has served as Co-Director of the Structural and Chemical Biology and Molecular Design Multidisciplinary Training Area of the Icahn School of Biomedical Sciences at Mount Sinai. He has served as a member of Faculty of 1000 and the Steering Committee of the Chemical Biology Discussion Group of the New York Academy of Sciences. He has been on the editorial boards of EMBO Reports and F1000 Research, and is a frequent peer reviewer for top-tier journals, including Nature, Cell, Science, and eLife, and for national and international funding agencies. Dr. Fisher has also been an ad hoc member of several NIH Study Sections.
Multi-Disciplinary Training AreasCancer Biology [CAB], Pharmacology and Therapeutics Discovery [PTD]
MD, Stanford University
PhD, Stanford University
My laboratory studies control of cell division and regulation of gene expression in eukaryotic cells, with a focus on the roles of protein phosphorylation by cyclin-dependent kinases (CDKs). CDKs were discovered because of their essential functions at the major transition points of the cell cycle: the commitment to duplicate genetic information by replication of DNA in S phase, and the decision to segregate the duplicated chromosomes to the two daughter cells in mitosis. Subsequently, CDK family members were found to regulate the transcription cycle of RNA polymerase (Pol) II (which transcribes protein-coding genes into mRNA), by phosphorylating the carboxyl-terminal domain (CTD) of Pol II to promote elongation, recruit regulatory proteins to the transcription complex, and coordinate RNA synthesis with co-transcriptional mRNA-processing events such as capping, splicing and polyadenylation.
We take a chemical-genetic approach to dissect the networks of CDKs and their targets involved in cell division and gene expression, both in yeast and mammalian cells. We created human cell lines and yeast strains that express only a mutant version of a particular CDK, which has been engineered to be analog-sensitive (AS)--susceptible to inhibition by bulky purine analogs that do not interfere with the functions of other, wild-type kinases. By modifying a single kinase in a cell, we can precisely determine its functions and targets. By combining mutations in more than one enzyme, we can determine the order of pathways that contain multiple CDKs, and uncover genetic interactions between separate CDK-containing pathways. In human colon cancer cells, we have targeted Cdk7, which has dual functions in cell cycle control and in transcription, to uncover its essential requirements at the entry to both S phase and mitosis, and to reveal its role in Pol II dynamics on actively transcribed genes in vivo. In the fission yeast Schizosaccharomyces pombe, we made AS versions of three different CDKs that phosphorylate the Pol II CTD with distinct but overlapping specificities; by inhibiting each CDK individually or in combinations, we defined an ordered, two-CDK pathway of phosphorylation that couples elongation with capping of the 5' end of a nascent transcript--a potential quality control mechanism reminiscent of the checkpoints that ensure the integrity and fidelity of genome transmission during mitotic cell division.
In our current work, we continue to expand our map of the CDK network, and to use chemical genetics--switching CDK activity ON and OFF in vivo with small molecules--to test predictions of network function generated by computational modeling. In this way, we hope to reveal new functions and targets of the network, and potentially promising targets for anticancer chemotherapy.
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Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Fisher during 2022 and/or 2023. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
- Kirilys Therapeutics, Inc.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.