Jennifer Kohler completed her undergraduate degree in Chemistry at Bryn Mawr College. Her Ph.D. studies, focused on the kinetics of protein-DNA interactions, were conducted in the laboratory of Prof. Alanna Schepartz, in the Chemistry Department at Yale University. From 2000-2004, Jennifer was an American Cancer Society postdoctoral fellow with Prof. Carolyn Bertozzi at the University of California, Berkeley. Research in the Kohler lab focuses on understanding the roles of glycoconjugates in a variety of biological systems.
Glycosylation is the elephant in the room of biomedical research. Estimates suggest that more than 50% of eukaryotic proteins are glycosylated, and new forms of protein glycosylation are still being discovered. Glycosylation is also a common feature of lipids, with at least 200 distinct glycolipid structures known in eukaryotes. Unconjugated polysaccharide chains are also abundant and diverse in structure. In fact, about 2% of human genes are involved in carbohydrate metabolism and glycosylation. Individual differences in glycosylation may underlie much of human variation. Clearly, evolution has favored an emphasis on glycosylation; however, the modern research environment is less conducive to focusing on carbohydrate-containing molecules.
Unfortunately, many of the biochemical and analytical techniques that are used to study protein-protein interactions are poorly suited to the study of glycosylated molecules. First, glycan-mediated interactions are typically low affinity and do not survive the rigorous purification steps often used to identify binding partners. Second, protein-centric methods do not take into account that fact that glycosylated proteins typically exist as a mixture of glycoforms, each of which may have unique binding properties and activities. Finally, in many techniques (yeast two-hybrid, heterologous expression systems) the critical glycans are either absent on altered.
My research group at UT Southwestern is committed to developing and implementing new tools that are optimized for the study of glycosylated molecules. In particular, we invested significant effort in the development of photocrosslinking sugar analogs that can be metabolically incorporated into cellular glycoconjugates and used to covalently crosslink glycan-mediated interactions. These tools can now be deployed to study and identify transient glycan-mediated interactions. Our current research efforts are focused in two broad areas: (1) sialic acid-containing glycoconjugates (sialosides); and (2) O-GlcNAc-modified proteins. We are currently using photocrosslinking sialic acid analogs to study the interactions of sialic acid-interacting proteins, particularly those involved in infectious disease and in cancer metastasis. We are using photocrosslinking GlcNAc to investigate the interactions of nucleoporins and other O-GlcNAc-modified proteins. In addition to our photocrosslinking studies, we have developed a new two-hybrid technique that can be used to interrogate protein-protein interactions in the Golgi and eukaryotic cells.
- Graduate School
- Yale University , Chemistry
- Graduate School
- Bryn Mawr College (1994), Chemistry
- chemical biology
- membrane proteins
- Enhanced crosslinking of diazirine-modified sialylated glycoproteins enabled through profiling of sialidase specificities.
- McCombs JE, Zou C, Parker RB, Cairo CW, Kohler JJ ACS Chem. Biol. 2015 Nov
- Enhanced transfer of a photocrosslinking GlcNAc analog by an O-GlcNAc transferase mutant with converted substrate specificity.
- Rodriguez AC, Yu SH, Li B, Zegzouti H, Kohler JJ J. Biol. Chem. 2015 Aug
- Cellular metabolism of unnatural sialic acid precursors.
- Pham ND, Fermaintt CS, Rodriguez AC, McCombs JE, Nischan N, Kohler JJ Glycoconj. J. 2015 May
- Recognition of diazirine-modified O-GlcNAc by human O-GlcNAcase.
- Rodriguez AC, Kohler JJ Medchemcomm 2014 Aug 5 8 1227-1234
- Glycosylation of the Nuclear Pore.
- Li B, Kohler JJ Traffic 2014 Jan
- Introduction to glycosylation and mass spectrometry.
- Patrie SM, Roth MJ, Kohler JJ Methods Mol. Biol. 2013 951 1-17
- Photocrosslinking approaches to interactome mapping.
- Pham ND, Parker RB, Kohler JJ Curr Opin Chem Biol 2012 Nov
- Sialidase specificity determined by chemoselective modification of complex sialylated glycans.
- Parker RB, McCombs JE, Kohler JJ ACS Chem. Biol. 2012 Sep 7 9 1509-14
- Photoaffinity probes for studying carbohydrate biology.
- Yu SH, Wands AM, Kohler JJ J Carbohydr Chem 2012 31 4-6 325-352
- Metabolism of diazirine-modified N-acetylmannosamine analogues to photo-cross-linking sialosides.
- Bond MR, Zhang H, Kim J, Yu SH, Yang F, Patrie SM, Kohler JJ Bioconjug. Chem. 2011 Sep 22 9
Mass Spectrometry of Glycoproteins: Methods and Protocols
Jennifer J. Kohler & Steven M. Patrie (Ed.) (2012). Humana Press
Honors & Awards
- Research Fellowship
Alfred P. Sloan Foundation (2009)
- Basil O’Connor Starter Scholar Research Award
March of Dimes (2007)
- CAREER Award
National Science Foundation (2007)
- New Faculty Award
Camille and Henry Dreyfus Foundation (2005)
- Society for Glycobiology (2007)
- American Chemical Society (1995)