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 Interest

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

Publications

Featured Publications LegendFeatured Publications

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
Chemical modulation of protein O-GlcNAcylation via OGT inhibition promotes human neural cell differentiation.
Andres LM, Blong IW, Evans AC, Rumachik NG, Yamaguchi T, Pham ND, Thompson P, Kohler JJ, Bertozzi CR ACS Chem. Biol. 2017 May
Effects of altered sialic acid biosynthesis on N-linked glycan branching and cell surface interactions.
Pham ND, Pang PC, Krishnamurthy S, Wands AM, Grassi P, Dell A, Haslam SM, Kohler JJ J. Biol. Chem. 2017 Apr
Modeled structural basis for the recognition of a2-3-sialyllactose by soluble Klotho.
Wright JD, An SW, Xie J, Yoon J, Nischan N, Kohler JJ, Oliver N, Lim C, Huang CL FASEB J. 2017 Apr
Soluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signaling.
Dalton G, An SW, Al-Juboori SI, Nischan N, Yoon J, Dobrinskikh E, Hilgemann DW, Xie J, Luby-Phelps K, Kohler JJ, Birnbaumer L, Huang CL Proc. Natl. Acad. Sci. U.S.A. 2017 Jan

Books

Featured Books Legend Featured Books

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)

Professional Associations/Affiliations

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