Jennifer Kohler, Ph.D.
Associate Professor

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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. 

Graduate School

Yale University , Chemistry

Graduate School

Bryn Mawr College (1994), Chemistry

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

Featured Publications

Fucosylated molecules competitively interfere with cholera toxin binding to host cells.

Wands AM, Cervin J, Huang H, Zhang Y, Youn G, Brautigam CA, Matson Dzebo M, Bjorklund P, Wallenius V, Bright DK, Bennett CS, Wittung-Stafshede P, Sampson NS, Yrlid U, Kohler JJ ACS Infect Dis 2018 Feb

GM1 ganglioside-independent intoxication by Cholera toxin.

Cervin J, Wands AM, Casselbrant A, Wu H, Krishnamurthy S, Cvjetkovic A, Estelius J, Dedic B, Sethi A, Wallom KL, Riise R, Bäckström M, Wallenius V, Platt FM, Lebens M, Teneberg S, Fändriks L, Kohler JJ, Yrlid U PLoS Pathog. 2018 Feb 14 2 e1006862

Fucosylation and protein glycosylation create functional receptors for cholera toxin.

Wands AM, Fujita A, McCombs JE, Cervin J, Dedic B, Rodriguez AC, Nischan N, Bond MR, Mettlen M, Trudgian DC, Lemoff A, Quiding-Järbrink M, Gustavsson B, Steentoft C, Clausen H, Mirzaei H, Teneberg S, Yrlid U, Kohler JJ Elife 2015 Oct 4

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

Photoactivatable crosslinking sugars for capturing glycoprotein interactions.

Tanaka Y, Kohler JJ J. Am. Chem. Soc. 2008 Mar 130 11 3278-9

Cell type and receptor identity regulate cholera toxin subunit B (CTB) internalization.

Sethi A, Wands AM, Mettlen M, Krishnamurthy S, Wu H, Kohler JJ, Interface Focus 2019 Apr 9 2 20180076

Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.

Toleman CA, Schumacher MA, Yu SH, Zeng W, Cox NJ, Smith TJ, Soderblom EJ, Wands AM, Kohler JJ, Boyce M Proc. Natl. Acad. Sci. U.S.A. 2018 May

Hyposialylated IgG activates endothelial IgG receptor Fc?RIIB to promote obesity-induced insulin resistance.

Tanigaki K, Sacharidou A, Peng J, Chambliss KL, Yuhanna IS, Ghosh D, Ahmed M, Szalai AJ, Vongpatanasin W, Mattrey RF, Chen Q, Azadi P, Lingvay I, Botto M, Holland WL, Kohler JJ, Sirsi SR, Hoyt K, Shaul PW, Mineo C J. Clin. Invest. 2017 Nov

A Conserved Splicing Silencer Dynamically Regulates O-GlcNAc Transferase Intron Retention and O-GlcNAc Homeostasis.

Park SK, Zhou X, Pendleton KE, Hunter OV, Kohler JJ, O'Donnell KA, Conrad NK Cell Rep 2017 Aug 20 5 1088-1099

Carb cutting works better with a partner.

Kohler JJ Nat. Struct. Mol. Biol. 2017 May 24 5 433-435

 Featured Books

Mass Spectrometry of Glycoproteins: Methods and Protocols

Jennifer J. Kohler & Steven M. Patrie (Ed.) (2012). Humana Press

• 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)