Nevan Krogan
Position
Associate Professor
Education
| Ph.D. | Medical Genetics | 1999-2005 | University of Toronto, Toronto, Canada |
| M.Sc. | Biochemistry | 1997-1999 | University of Regina, Regina, Canada |
| B.Sc. | Chemistry | 1993-1997 | University of Regina, Regina, Canada |
Work History
| 2009-Present: | Associate Professor, Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA. |
| 2007-2009: | Assistant Professor, Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA. |
| 2006-2007: | Sandler Fellow, UCSF, San Francisco, CA. |
Research Interests
Our research focuses on the development of tools that allow for the generation, analysis and visualization of large-scale, quantitative genetic and physical interaction maps with the ultimate goal of further understanding cell physiology. Our work has been targeted towards simpler systems (e.g. S. cerevisiae, S. pombe and E. coli) but we plan to eventually apply these approaches to multiple-cellular organisms.
In the past, we have used an affinity purification/mass spectrometry strategy to try to comprehensively define the physical interactome of S. cerevisiae. Recently developed algorithms have allowed us to define a relatively comprehensive, high-quality protein-protein interaction dataset for budding yeast. We are employing similar strategies to create protein-protein interaction maps for other organisms including S. pombe, M. tuberculosis as well as an HIV-host physical map.
However, even knowledge of the stoichiometry, affinity, and lifetime of every protein-protein interaction would not reveal the functional relationships between and within such complexes. Genetic interactions can provide functional information that is largely invisible to protein-protein interaction datasets. In collaboration with Jonathan Weissman, we have developed an approach, termed E-MAP (epistatic miniarray profile), which can provide information on genetic interactions. E-MAPs comprise comprehensive and quantitative measurements of genetic interactions between pairs of mutations from a set of genes that are functionally related. Since this analysis is quantitative, both negative (i.e. SSL) and positive interactions can be identified. Positive interactions include cases where the double mutant grows better (suppression) or no worse than the sickest single mutant. Such positive interactions would result, for example, if loss of one protein suppressed the growth defect caused by loss of a second protein or if two proteins are part of a pathway whose function is completely dependent on the presence of both components. We have used the E-MAP approach to genetically interrogate sets of genes involved in the early secretory pathway and chromosome function, which includes transcriptional regulation, DNA repair/replication and chromatid segregation. We are presently generating E-MAPs that focus on other biological processes and developing E-MAP technology for other organisms.
Finally, and most importantly, we attempt to integrate the physical and genetic interaction data in a biologically meaningful way so that hypotheses about specific biological phenomenon can be generated and ultimately tested.
Select Publications
Schuldiner M, Collins SR, Thompson NJ, Denic V, Bhamidipati A, Punna T, Ihmels J, Andrews B, Boone C, Greenblatt JF, Weissman JS, Krogan NJ. 2005. Exploration of the function and organization of the yeast early secretory pathway through an epistatic mini array profile (E-MAP). Cell, 123:507-519. [Pubmed]
Keogh MC, Kurdistani SK, Morris SA, Ahn SH, Podolny V. Collins SR, Schuldiner M, Chin K, Punna T, Thompson NJ, Boone C, Emili A, Weissman JS, TR, Strahl BD, Grunstein M, Greenblatt JF, Buratowski S, Krogan NJ. 2005. Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell, 123:593-605. [Pubmed]
Keogh MC, Kim J, Downey M, Fillingham J, Chowdbury D, Harrison JC, Onishi M, Datta N, Galicia S, Emili A, Lieberman J, Shen X, Buratowski S, Haber JE, Durocher D, Greenblatt JF, Krogan NJ. 2006. A phosphatase complex required for dephosphorylation of γH2A.X and DNA damage checkpoint recovery in S. cerevisiae. Nature, 439:497-501. [Pubmed]
Krogan NJ, Cagney G, Yu H, Zhong G, Guo X, Ignatchenko A, Li J, Pu S, Datta N, Tikuisis AP, Punna T, Peregrin-Alvarez JM, Shales M, Zhang X, Davey M, Robinson MD, Paccanaro A, Bray JE, Sheung A, Beattie B, Richards DP, Canadien V, Lalev A, Mena F, Wong P, Starostine A, Canete MM, Vlasblom J, Wu S, Orsi C, Collins SR, Chandran S, Haw R, Rilestone J, Gandi K, Thompson NJ, Musso G, St. Onge P, Ghanny S, Lam MHY, Butland G, Altaf A, Kanaya S, Shilatifard A, O’Shea E, Weissman JS, Ingles CJ, Hughes TR, Parkinson J, Gerstein M, Wodak SJ, Emili A, Greenblatt JF. 2006. Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature, 440:637-643. [Pubmed]
Collins SR, Miller KM, Maas NL, Roguev A, Schuldiner M, Fillingham J, Chu CS, Gebbia M, Recht J, Shales M, Ding H, Xu H, Han J, Ingvarsdottir K, Cheng B, Han J, Andrews B, Berger SL, Hieter P, Zhang Z, Brown GW, Ingles CJ, Boone C, Emili A, Allis CD, Toczyski DP, Weissman JS, Greenblatt JF, Krogan NJ. 2007. Functional dissection of yeast chromosome biology complexes using a genetic interaction map. Nature, 446: 806-810. [Pubmed]
Roguev A, Bandyopadhyay S, Zofall M, Zhang K, Fischer T, Collins SR, Qu H, Shales M, Park HO, Hayles J, Hoe KL, Kim DU, Ideker T, Grewal SI, Weissman JS, Krogan NJ. 2008. Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast. Science, 322(5900):405-10. [Pubmed]
Nagai S, Dubrana K, Tsai-Pflugfelder M, Davidson MB, Roberts TM, Brown G, Varela E, Hediger F, Gasser SM, Krogan NJ. 2008. Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase, Science, 322:597-602. [Pubmed]
Wilmes GM, Bergkessel M, Bandyopadhyay S, Shales M, Braberg H, Cagney G, Collins SR, Whitworth GB, Kress TL, Weissman JS, Ideker T, Guthrie C, Krogan NJ. 2008. A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing. Mol. Cell, 32(5):735-46. [Pubmed]
Fiedler D, Braberg H, Mehta M, Chechik G, Cagney G, Mukherjee P, Silva AC, Shales M, Collins SR, van Wageningen S, Kemmeren P, Holstege FC, Weissman JS, Keogh MC, Koller D, Shokat KM, Krogan NJ, 2009. Functional organization of the S. cerevisiae phosphorylation network. Cell, 136(5):952-63. [Pubmed]
Beltrao P, Trinidad JC, Fiedler D, Roguev A, Lim WA, Shokat KM, Burlingame AL, Krogan NJ, 2009. Evolution of phosphoregulation: Comparison of phosphorylation patterns across yeast species. PLoS Biology, 7(6):e1000134. [Pubmed]