Dr. Jeff Ranish
Ph.D., Molecular and Cellular Biology Program
University of Washington, 1999
Dr. Jeff Ranish joined the Institute for Systems Biology (ISB) faculty in 2005. He comes to the ISB with a strong background in the disciplines of proteomics, molecular biology and biochemistry. He has a longstanding interest in understanding how proteins function in complex biological systems. Dr. Ranish is dedicated to pursuing this goal by developing and applying state-of-the-art proteomics technologies to probe the composition of macromolecular complexes, with a particular interest in transcriptional regulatory complexes.
During his doctoral dissertation, Dr. Ranish studied the molecular mechanism of transcription initiation by RNA polymerase II in the laboratory of Dr. Steven Hahn at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Using the yeast Saccharomyces cerevisiae, he applied biochemical, molecular biology, and molecular genetics approaches to address this problem. Dr. Ranish´s studies culminated in the identification and cloning of the genes encoding the general transcription factor TFIIA, and the development of an immobilized promoter system for isolating and studying transcription complexes. He used this system to define intermediates in the formation of preinitiation complexes, and to define the re-initiation complex. For his poct-doctoral training, Dr. Ranish worked with Dr. John Yates, III and Dr. Ruedi Aebersold in the Molecular Biotechnology department at the University of Washington. There he developed his skills in mass spectrometry based-proteomic technologies. Dr. Ranish joined Dr. Aebersold when Dr. Aebersold left the University of Washington to found the ISB in 2000.
During his tenure in Dr. Aebersold´s lab, Dr. Ranish developed a new strategy for studying macromolecular complexes by quantitative mass spectrometry. The strategy can be used to determine the composition of complexes and to detect changes in complex composition. It is based on the use of stable isotope tagging of proteins and mass spectrometry to compare the relative abundances of tryptic peptides derived from suitable pairs of purified or partially purified protein complexes. Bona-fide complex components are identified by their increased abundance in a specific purification compared to a nonspecific purification. Changes in complex composition can be detected by comparing the abundance ratios of proteins in complexes that are isolated from cells grown under different conditions. Application of the technology to study transcription factor complexes from yeast and higher eukaryotes has resulted in the discovery of new transcription factors with roles in human health, and has revealed mechanisms for how genes are regulated during development. The usefulness of the approach is apparent from the extensive local, national, and international collaborations in which Dr Ranish engages.
Research Areas:
Research in Dr. Ranish´s lab focuses on understanding the function and regulation of macromolecular complexes involved in processes like transcription by RNA polymerase II. Transcription by RNA Polymerase II is one of the first steps in gene expression, and as such, it is a central process in the control of a cell´s ability to grow and respond to the environment. It involves the interaction of a plethora of factors with the core transcription machinery and the chromatin template. These factors include activators, co-activators, repressors, co-repressors, chromatin remodeling complexes and chromatin modifying complexes. In all, more than 100 polypeptides are known to be involved in this process.
Despite the identification of all these proteins, we still lack a clear understanding of the role of individual factors in transcription, and how the expression of specific genes is regulated. Studies in Dr. Ranish´s lab are directed at answering these questions by probing the composition of gene-specific transcription complexes and determining how their composition changes over time and in response to genetic and environmental perturbations. Ultimately, the results of these studies will be used in models that attempt to predict how organisms respond to their environment.
Key collaborations within ISB:
Aderem Lab - Quantitative proteomic characterization of transcriptional regulatory complexes that control the innate immune response
Aebersold Lab -Development and application of new stable isotope labeling strategies to study macromolecular complexes
Aitchison Lab - Quantitative proteomic characterization of transcriptional regulatory complexes that control peroxisomal gene expression
Balig Lab - Quantitative proteomic characterization of transcriptional regulatory complexes in Halobacterium
Galitski Lab - Quantitative proteomic characterization of transcriptional regulatory complexes that control yeast filamentation
Hood Lab - Development of glycopeptide capture technology
Key collaborations outside ISB:
Externally, the Ranish lab has collaborations with institutions locally, nationally and worldwide. Notably, there are collaborations with:
Steve Hahn and Sue Biggins at the Fred Hutchinson Cancer Research Center, Seattle, Washington
Steve Hauschka and Ted Young at the University of Washington,Seattle, Washington
Gerald Crabtree at Stanford University, Palo Alto, California
Geoffrey Rosenfeld at University of California San Diego
Lee Kraus at Cornell University, Ithaca, New York
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