Jennifer Kohler, Ph.D.

Assistant Professor

Department: Biochemistry

Graduate Programs: Biological Chemistry

Biography

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Biography

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.

Research summary

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. 

Education

Graduate School Yale University (), Chemistry
Graduate School Bryn Mawr College (1994), Chemistry

Research Interests

  • carbohydrates
  • chemical biology
  • glycobiology
  • Golgi
  • membrane proteins

Publications

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Featured Publications

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

Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified proteins to their binding partners.

Yu SH, Boyce M, Wands AM, Bond MR, Bertozzi CR, Kohler JJ Proc. Natl. Acad. Sci. U.S.A. 2012 Mar 109 13 4834-9

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

Modified GM3 gangliosides produced by metabolic oligosaccharide engineering.

Whitman CM, Yang F, Kohler JJ Bioorganic & medicinal chemistry letters 2011 May 5006-10

Metabolic cross-talk allows labeling of O-linked beta-N-acetylglucosamine-modified proteins via the N-acetylgalactosamine salvage pathway.

Boyce M, Carrico IS, Ganguli AS, Yu SH, Hangauer MJ, Hubbard SC, Kohler JJ, Bertozzi CR Proc. Natl. Acad. Sci. U.S.A. 2011 Feb 108 8 3141-6

Metabolically incorporated photocrosslinking sialic acid covalently captures a ganglioside-protein complex.

Bond MR, Whitman CM, Kohler JJ Mol Biosyst 2010 Oct 6 10 1796-9

Results 1-10 of 32

Books

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Featured Books

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)

Professional Associations/Affiliations

  • Society for Glycobiology (2007)
  • American Chemical Society (1995)