Kessler Group
In our group, we are focused on using proteomics, mass spectrometry and biochemical approaches to understand disease processes.
Proteomics and Mass spectrometry
The group has expertise in proteomics based methodologies and hosts a platform containing a variety of chromatography equipment and mass spectrometers. We collaborate with many researchers across the campus and elsewhere, applying this methodology to biomedical problems.
Ubiquitin and Protease Biology
We are particularly interested in using cell biological, biochemical and mass spectrometry approaches to study the biology of ubiquitin processing enzymes and other proteases. We are also interested in understanding their role in immunity and cancer related disease pathologies.
Regulation of the lifespan of proteins is key for most biological processes and when altered, can often associate with progression of diseases. When proteins reach the end of their lifetime, most of them get modified by the attachment of ubiquitin, a small protein of 76 amino acids. This modification has been implicated not just in the elimination of damaged proteins, but also in physiological proteolytic control of processes such as transcription, signal transduction, and cell cycle transitions. So far, analysis has principally focused on ubiquitin (ub) attachment, with several hundred ub conjugating enzymes characterized to date. Much less is known about enzymes that remove ub from substrate proteins, yet around a hundred genes have been identified, sharing consensus motifs for deubiquitylating enzymes (DUBs). Such diversity is inconsistent with a simple recycling function and strongly suggests a range of specific (but currently largely undiscovered) biological functions. Members of the DUB family are already known to contribute to neoplastic transformation and are implicated in neurodegenerative diseases, making them attractive targets for drug design.
Key Publications
2012. ATM-Dependent Downregulation of USP7/HAUSP by PPM1G Activates p53 Response to DNA Damage. Mol Cell. View Article
Altun M, Kramer HB, Willems LI, McDermott JL, Leach CA, Goldenberg SJ, Suresh Kumar KG, Konietzny R, Fischer R, Kogan E, Mackeen MM, McGouran J, Khoronenkova SV, Parsons J, Dianov GL, Nicholson B, Kessler BM. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol. 2011. 18(11):1401-1412. View Article. Press Release
Parsons JL, Dianova II, Khoronenkova SV, Edelmann MJ, Kessler BM, Dianov GL. USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase β. Mol Cell. 2011 Mar 4;41(5):609-15. View article
Kramer HB, Lavender KJ, Qin L, Stacey AR, Liu MK, di Gleria K, Simmons A, Gasper-Smith N, Haynes BF, McMichael AJ,Borrow P, Kessler BM. Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection. PLoS Pathog. 2010 May 6;6(5):e1000893. View article
Mackeen MM, Kramer HB, Chang KH, Coleman ML, Hopkinson RJ, Schofield CJ, Kessler BM. Small molecule-based inhibition of histone demethylation in cells assessed by quantitative mass spectrometry. J Proteome Res. 2010 Aug 6;9(8):4082-92. View article
Edelmann MJ, Kramer HB, Altun M, Kessler BM. Post-translational modification of the deubiquitinating enzyme otubain 1 modulates active RhoA levels and susceptibility to Yersinia invasion. FEBS J. 2010 Jun;277(11):2515-30. View article
Edelmann MJ, Iphoefer A, Masato A, Kramer H, Dhe-Paganon S, Kessler BM. Structural basis and functional specificity of otubain 1 mediated deubiquitylation. 2009. Biochem J. 418(2): 379-90. View article
Xu D, Suenaga N, Edelmann MJ, Fridman R, Muschel MJ, Kessler BM. Novel MMP-9 substrates in cancer cells revealed by a label-free quantitative proteomics approach. Mol Cell Proteomics. 2008. Nov;7(11):2215-28. View article
Borodovsky A, Ovaa H, Kolli N, Gan-Erdene T, Wilkinson KD, Ploegh HL, Kessler BM. Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme family. Chem Biol. 2002, 1149-59. View article