Kohler, Jennifer - UT Southwestern Medical Center

个人简介

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

研究领域

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. carbohydrates chemical biology glycobiology Golgi membrane proteins

近期论文

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Rodriguez, AC & Kohler, JJ. Recognition of diazirine- modified O-GlcNAc by human O-GlcNAcase. Med. Chem. Comm., (2014) 5(8): 1227- 1234. Fujita, A & Kohler, JJ. "Metabolism of Natural and Unnatural Sialic Acid." Glycoscience: Biology and Medicine. In press. McCombs, JE & Kohler, JJ. "Chemoselective reactions for glycan labeling," Chemoselective and Bioorthogonal Ligation Chemistries: Concepts and Applications. Edited by R Algar, P Dawson, I Medintz. Wiley-VCH: Weinheim, Germany. In press. Li, B & Kohler, JJ. Glycosylation of the Nuclear Pore. Traffic, (2014) 15: 347- 31. Kohler, JJ & Patrie SM, eds. Mass Spectrometry of Glycoproteins: Methods and Protocols, Methods in Molecular Biology Series (2012) Humana Press. Available November 2012. Pham, ND, Parker RB & Kohler JJ. Photocrosslinking approaches to interactome mapping. Curr. Op. Chem. Biol., (2012) 17: 1- 12. Parker, RB, McCombs, JE & Kohler, JJ. Sialidase specificity determined by chemoselective modification of complex sialylated glycans. ACS Chemical Biology (2012) 7: 1509-1514. Yu, S-H, Wands, AM & Kohler, JJ. Photoaffinity probes for studying carbohydrate biology. Journal of Carbohydrate Chemistry (2012) 31: 325-352. Yu, S-H, Boyce, M, Wands, AM, Bond, MR, Bertozzi, CR, & Kohler, JJ.Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified proteins to their binding partners, Proc. Natl. Acad. Sci. USA, (2012) 109: 4834-4839. Bond, MR, Zhang, H, J Kim, Yu, S-H, Yang, F, Patrie, S, & Kohler, JJ.Metabolism of diazirine-modified N-acetylmannosamine analogs to photocrosslinking sialoside, Bioconjugate Chemistry, (2011) 22: 1811-1823. Whitman, CM, Yang, F, & Kohler, JJ. Modified GM3 gangliosides produced by metabolic oligosaccharide engineering, Bioorganic & Medicinal Chemistry, (2011) 21: 5006–5010. Boyce, M, Carrico, IS, Ganguli, AS, Yu, S-H, Hangauer, MJ, Hubbard, SC, Kohler, JJ & Bertozzi, CR. Metabolic crosstalk allows labeling of human O-linked β-N-acetylglucosamine-modified proteins via the N-acetylgalactosamine salvage pathway, Proc. Natl. Acad. Sci. USA, (2011) 108: 3141-3146. Dube, DH, Li, B, Greenblatt, EJ, Nimer, S, Raymond, AK, & Kohler, JJ. A two-hybrid assay to study protein interactions within the secretory pathway,PLoS ONE (2010) 5: e15648. Kohler, JJ. Post-translational modifications: A shift for the O-GlcNAc paradigm (News & Views)., Nat. Chem. Biol., (2010) 5: 634-635. Bond, MR, Whitman, CM, & Kohler, JJ. Metabolically incorporated photocrosslinking sialic acid covalently captures a ganglioside-protein complex, Molecular Biosystems (2010) 6: 1796-1799. Yu, S-H, Bond, MR, Whitman, CM, & Kohler, JJ. Metabolic labeling of glycoconjugates with photocrosslinking sugars, Methods in Enzymology(2010) 478: 541-562. Whitman, CM, Bond, MR, & Kohler, JJ. Chemical glycobiology (Book Chapter), Comprehensive Natural Products Chemistry II (2010). Parker, RB & Kohler, JJ. Regulation of intracellular signaling by extracellular glycan remodeling, ACS Chemical Biology (2010) 5: 35-46. Desko, MM, Gross, DA, & Kohler, JJ. Effects of N-glycosylation on the activity and localization of GlcNAc-6-sulfotransferase 1, Glycobiology, (2009) 19: 1068-1077. Kohler, JJ. Aniline: a catalyst for sialic acid detection, ChemBioChem, (2009) 10: 2147-2150.