Baar, Keith - University of California, Davis - College of Biological Sciences

研究领域

Muscle hypertrophy How resistance exercise is sensed by muscle and how does it lead to an increase in protein synthesis and muscle mass? Research from our laboratory has identified the mammalian target of rapamycin (mTORC1)/S6 protein kinase (S6K1) pathway as the central mechanism involved in physiological hypertrophy of skeletal muscle in response to resistance exercise. It is now clear that resistance exercise activates mTORC1 and that this activation is important in increasing muscle's capacity to boost protein synthesis. By studying the control of rDNA synthesis, we hope to identify molecules that are critical for this process and that can reproduce the increase in muscle mass without the need for the exercise stimulus Muscular endurance How is endurance exercise transduced into changes in mitochondrial mass and fatigue resistance? Unlike resistance exercise, endurance exercise results in a coordinated genetic response that increases aerobic capacity. Our laboratory and others have identified a central transcriptional cofactor that is activated following a single bout of aerobic exercise. The peroxisome proliferative activated receptor, gamma coactivator (PGC)-1α is a master regulator of mitochondrial biogenesis and enzymes of fatty acid metabolism. It is now clear that many stimuli converge on PGC-1 and that a number of these molecules also inhibit the activation of the mTORC1/S6K1 pathway. Understanding this interplay will be essential if we are to develop genetic or pharmacological interventions to create bigger, stronger, and more fatigue resistant muscles. Ligament engineering Can we engineer ligaments to replace people's damaged ACLs? In our bodies, ligaments connect bone to bone, are essential to normal movement and do not repair very well. We have developed a series of calcium phosphate based cements that we are using to recreate the ligament to bone connection. Our engineered ligaments are developmentally similar to embryonic ligament. Using these constructs and our calcium phosphate cements, we have engineered the first in vitro ligament (bone-ligament-bone) with the hope of implanting these tissues into animals and in the future using them to repair ligaments in humans after rupture.

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Khodabukus A., and K. Baar. The effect of serum origin on tissue engineered skeletal muscle function.J Cell Biochem. 2014 Dec;115(12):2198-207. Hamilton D.L., A. Philp, M.G. MacKenzie, A. Patton, M.C. Towler, I.J. Gallagher, S.C. Bodine, and K. Baar. Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation. Am J Physiol Endocrinol Metab. 2014 Aug 15;307(4):E365-73. McGee S.L., C. Swinton, S. Morrison, V. Gaur, D.E. Campbell, S.B. Jorgensen, B.E. Kemp, K. Baar, G.R. Steinberg, and M. Hargreaves. Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress. FASEB J. 2014 Aug;28(8):3384-95. Mackenzie, M.G., D.L. Hamilton, M. Pepin, A. Patton, and K. Baar. Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise. PLoS One. 2013 Jul 2;8(7):e68743. Timmons, J.A., K. Baar, P. Davidsen, and P.J. Atherton. Is irisin a human exercise gene? Nature. 2012 488(7413): E9-10 Park, S.J., F. Ahmad, A. Philp, K. Baar, T. Williams, H. Luo, H. Ke, H. Rehmann, R. Taussig, A.L. Brown, M.K. Kim, M.A. Beaven, A.B. Burgin, V. Manganiello, J.H. Chung. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012 Feb 3;148(3):421-33. Philp, A., M.G. MacKenzie, M.Y. Belew, M.C. Towler, A. Corstorphine, A. Papalamprou, D. G. Hardie, and K. Baar. Glycogen Content Regulates Peroxisome Proliferator Activated Receptor-∂ (PPAR-∂) Activity in Rat Skeletal Muscle. PLOS ONE Oct 17;8(10):e77200. Paxton J.Z., L.M. Grover, and K. Baar. Engineering an In Vitro Model of a Functional Ligament from Bone to Bone. Tissue Eng Part A. 2010 Nov;16(11):3515-25. Hulston, C.J., M.C. Venables, C.H. Mann, C. Martin, A. Philp, K. Baar, and A.E. Jeukendrup. Training with low muscle glycogen enhances adaptations in fat metabolism in well-trained cyclists. Med Sci Sports Exerc. 2010 Nov;42(11):2046-55. MacKenzie, M.G., D.L. Hamilton, J.T. Murray, P.M. Taylor, and K. Baar. mVps34 is activated following high-resistance contractions. J Physiol. 2009 Jan 15;587(Pt 1):253-60. Baar, K., R. Birla, M.O. Boluyt, G.H. Borschel, E.M. Arruda, and R.G. Dennis. Heart muscle by design: self-organization of rat cardiac cells into contractile 3-D cardiac tissue. FASEB J. 2005 Feb;19(2):275-7. Calve, S.C., R.G. Dennis, P.E. Kosnik II, K. Baar, K. Grosh and E.M. Arruda. Engineering of functional tendon. Tissue Engineering 2004 10(5/6): p. 755-761. Baar, K., A.R. Wende, T.E. Jones, M. Marison, L.A. Nolte, M. Chen, D.P. Kelly, and J.O. Holloszy. Adaptation of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J. 2002 16: 1879-1886. Baar, K., and K. A. Esser. Activation of p70S6k correlates with skeletal muscle hypertrophy in the rat. Amer. J. Physiol. 1999, 276 (Cell Physiol. 45): C120-C127.