Klip, Amira - University of Toronto - Department of Biochemistry

个人简介

Following her PhD in Biochemistry (on the use of photolabels to study protein structure/function) Dr. Klip did 2 years of postdoctoral studies at The University of Toronto with Dr. D. MacLennan followed by 1 year at the ETH in Zurich with Dr. G. Semenza. This turned her interest to membrane transport proteins, SERCA and SGLT. In 1980 Dr. Klip was appointed as Scientist at SickKids and began her independent career on the regulation of glucose transport by the other family of mammalian transporters, GLUTs. This led her to investigating insulin signal transduction and set her lab on a path to unravel the signals from the insulin receptor to the responding glucose transporters. In parallel, she characterized biochemically the muscle glucose transporter (GLUT4) and discovered its regulation by insulin and exercise through distinct recruitment mechanisms. Her lab’s signal transduction studies revealed the unexpected involvement of the small molecular G proteins Rac1, Rab 8 and Rab13 as molecular switches linking to mechanical effectors mobilizing GLUT4-containing vesicles. In addition to normal insulin action the Klip lab also investigated insulin resistance, its molecular origins and complex causes in the body resulting from lipid overload and obesity. They currently study how immune cells become inflamed in obesity and how they impact on muscle cells. They recently discovered that saturated lipids turn macrophages inflammatory and products thereof in turn activate signals within muscle cells that interfere with insulin signalling. Conversely, saturated fatty acids make muscle cells express pannexins that release nucleotides which chemoattract monocytes. This cellular crosstalk may underpin their observed infiltration of muscle by immune cells during obesity and its contribution to insulin resistance. This work was performed by over 70 graduate students and fellows, that she mentors with passion. Dr. Klip was an Associate Chief of Research at SickKids for over 15 years, where she created and directed for 14 years the Research Training Centre as a hub of information and opportunities for students and fellows of all disciplines. She has organized international meetings, is a past Editor-in-Chief of the American Journal of Physiology-Endocrinology & Metabolism, and continues to serve on a number of editorial boards, as well as on national and international grant panels. Her work is supported by CIHR, the Canadian Diabetes Association and the Banting and Best Diabetes Centre. Klip holds a Tier I Canada Research Chair on the Cell Biology of Insulin Action.

近期论文

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Calcium signaling in insulin action on striated muscle. Contreras-Ferrat A, Lavandero S, Jaimovich E, Klip A. Cell Calcium. 2014 Sep 6. pii: S0143-4160(14)00135-3. Read Nucleotides released from palmitate-challenged muscle cells through pannexin-3 attract monocytes. Pillon NJ, Li YE, Fink LN, Brozinick JT, Nikolayev A, Kuo MS, Bilan PJ, Klip A. Diabetes. 2014 Nov;63(11):3815-26. Read Mice lacking NOX2 are hyperphagic and store fat preferentially in the liver. Costford SR, Castro-Alves J, Chan KL, Bailey LJ, Woo M, Belsham DD, Brumell JH, Klip A. Am J Physiol Endocrinol Metab. 2014 Jun 15;306(12):E1341-53. Read Dynamic GLUT4 sorting through a syntaxin-6 compartment in muscle cells is derailed by insulin resistance-causing ceramide. Foley KP, Klip A. Biol Open. 2014 Apr 4;3(5):314-25. Read