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Department of Physiology and Membrane Biology

Department of Physiology and Membrane Biology

Keith Baar, Ph.D.

Keith Baar, Ph.D.

Associate Professor
174 Briggs Hall
Davis Campus
(530) 752-3367
e-mail

Graduate Group Affiliations

Molecular, Cellular and Integrated Physiology

Research Interests

The goal of my laboratory is to understand the molecular determinants of musculoskeletal development and the role of exercise in improving health and performance. To achieve this goal, we work on muscle, tendon, and ligaments from 2- and 3-dimensional tissue culture, in vivo wild type and genetically modified animals, and humans. Of particular interest are: 1) the interplay between nutrition and exercise and the mammalian target of rapamycin complex 1 (mTORC1) in the maintenance of muscle mass; 2) the role of the amino acid transceptor LAT1 in the activation of protein synthesis and maintenance of muscle mass; 3) the mechanism of ER stress-induced loss of protein synthesis and how this leads to anabolic resistance in muscle; and 4) the role of growth factors and loading on the activation of the Egr-1 transcription factor and the development and mechanics of ligaments. Our laboratory discovered that mTORC1 was activated by resistance exercise and that this correlates with the degree of skeletal muscle hypertrophy. Since then, we have focused on mTORC1 and its regulation by loading and nutrients. We have shown that: 1) mTORC1 is activated directly by load in a growth factor-independent manner; 2) a1-AMPK regulates mTORC1 activity during overload; 3) following a high fat diet the unfolded protein response, through inhibition of PKB, can attenuate mTORC1 activation; and 4) muscle signaling and protein synthesis after exercise are modified by nutritional interventions that are rich in leucine. Our laboratory has also developed a number of 2- and 3-dimensional tissue culture assays that can be used to study the effects of genes and nutrients on muscle, tendon, and ligament function. These studies have taught us the techniques necessary to generate, and maintain knockout mice, and perform in vivo resistance exercise, and nutritional interventions, and develop novel interventions that are directly relevant to human health and performance.

For more information, please visit: The Functional Molecular Biology Lab

 

Representative Publications

2014  McGee SL, Swinton C, Morrison S, Gaur V, Campbell DE, Jorgensen SB, Kemp BE, Baar K, Steinberg GR, Hargreaves M. Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress. FASEB J. 2014 Apr 14. [Epub ahead of print]

2014  Wecksler, A.T., S.H. Hwang, H.I. Wettersten, J.E. Gilda, A. Patton, L.J. Leon, K.L. Carraway 3rd, A.V. Gomes, K. Baar, R.H. Weiss, B.D. Hammock. Novel sorafenib-based structural analogues: in-vitro anticancer evaluation of t-MTUCB and t-AUCMB. Anticancer Drugs. 2014 Apr;25(4):433-46.

2013  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 2013 Oct 17;8(10):e77200.

2013  Hwee D.T., L.M. Baehr, A. Philp, K. Baar, and S.C. Bodine. Maintenance of muscle mass and load-induced growth in Muscle RING Finger 1 null mice with age. Aging Cell. 2013. EPub.

2013  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.

2012  Timmons, J.A., K. Baar, P. Davidsen, and P.J. Atherton. Is irisin a human exercise gene? Nature. 2012 488(7413): E9-10

2012  Hagerty, P., A. Lee, S. Calve, C.A. Lee, M. Vidal, and K. Baar. The effect of growth factors on both collagen synthesis and tensile strength of engineered human ligaments. Biomaterials. 2012 Sep;33(27):6355-61.

2012  Churchward-Venne, T.A., N.A. Burd, C.J. Mitchell, D.W. West, A. Philp, G.R. Marcotte, S.K. Baker, K. Baar, and S.M. Phillips. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2012 Jun 1;590(Pt 11):2751-65.

2012  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.

2012  Khodabukus, A., and K. Baar. Defined electrical stimulation emphasizing excitability for the development and testing of engineered skeletal muscle. Tissue Eng Part C Methods. 2012 May;18(5):349-57.

2012  Paxton J.Z., P. Hagerty, J.J. Andrick, and K. Baar. Optimizing an intermittent stretch paradigm using ERK1/2 phosphorylation results in increased collagen synthesis in engineered ligaments. Tissue Eng Part A. 2012 Feb;18(3-4):277-84.

2011  Schenk S., C.E. McCurdy, A. Philp, M.Z. Chen, M.J. Holliday, G.K. Bandyopadhyay, O. Osborn, K. Baar, and J.M. Olefsky. Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction. J Clin Invest. 2011 Nov 1;121(11):4281-8.

2011  Philp, A., M.Y. Belew, A. Evans, D. Pham, I. Sivia, A. Chen, S. Schenk, and K. Baar. The PGC-1a related co-activator (PRC) promotes mitochondrial and myogenic adaptations in C2C12 myotubes. Am J Physiol Regul Integr Comp Physiol. 2011 Oct;301(4):R864-72.

2011  Philp, A., A. Chen, D. Lan, G.A. Meyer, A.N. Murphy, A.E. Knapp, I.M. Olfert, C.E. McCurdy, G.R. Marcotte, M.C. Hogan, K. Baar, and S. Schenk. Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator activated receptor g coactivator-1a (PGC-1a) deacetylation following endurance exercise. J Biol Chem. 2011 Sep 2;286(35):30561-70.

2011  Breen, L., A. Philp, O.C. Witard, S.R. Jackman, A. Selby, K. Smith, K. Baar, and K.D. Tipton. The influence of carbohydrate-protein co-ingestion following endurance exercise on myofibrillar and mitochondrial protein synthesis. J Physiol. 2011 Aug 15;589(Pt 16):4011-25.

2011  Deldicque L., L. Bertrand, A. Patton, M. Francaux, and K. Baar. ER Stress Induces Anabolic Resistance in Muscle Cells through PKB-Induced Blockade of mTORC1. PLoS ONE 2011 6(6): e20993.

2011  Preston, R.S., A. Philp, T. Claesens, E.A. Dunlop, L. Gijezen, K.T. Harper, T. Brinkhuizen, D.M. Davies, S.S. Land, K. Baar, M. van Steensel and A.R. Tee. Absence of the Birt-Hogg-Dubé gene product is associated with increased Hypoxia Inducible Factor transcriptional activity and a loss of metabolic flexibility. Oncogene, 2011 Mar 10;30(10):1159-73.

2010  Hamilton D.L., A. Philp, M.G. MacKenzie, and K. Baar. A limited role for PI(3,4,5)P3 regulation in controlling skeletal muscle mass in response to resistance exercise. PLoS One. 2010 Jul 16;5(7):e11624.

2010  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.

2010  Deldicque L, P.D. Cani, A. Philp, J.M. Raymackers, P.J. Meakin, M.L. Ashford, N.M. Delzenne, M. Francaux, and K. Baar. The unfolded protein response is activated in skeletal muscle by high-fat feeding: potential role in the down-regulation of protein synthesis. Am J Physiol Endocrinol Metab. 2010 Nov;299(5):E695-705.

2010  Bayer M.L., C.Y. Yeung, K.E. Kadler, K. Qvortrup, K. Baar, R.B. Svensson, S.P. Magnusson, M. Krogsgaard, M. Koch M, and M. Kjaer. The initiation of embryonic-like collagen fibrillogenesis by adult human tendon fibroblasts when cultured under tension. Biomaterials. 2010 Jun;31(18):4889-97.

2010  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.

2009  Khodabukus, A., and K. Baar. Regulating Fibrinolysis to Engineer Skeletal Muscle from the C2C12 Cell Line. Tissue Eng Part C Methods. 2009 Sep;15(3):501-11.

2009  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.

2009  Paxton, J.Z., K. Donnelly, R.P. Keatch, and K. Baar. Engineering the Bone-Ligament Interface Using Polyethylene Glycol Diacrylate Incorporated with Hydroxyapatite. Tissue Eng Part A. 2009 Jun;15(6):1201-9.

2008  Kapacee, Z., S.H. Richardson, Y. Lu, T. Starborg, D.F. Holmes, K. Baar, and K.E. Kadler. Tension is required for fibripositor formation. Matrix Biology, 2008 27:371–375.

2008  McGee, S.L., K.J. Mustard, D.G. Hardie, and K. Baar. Normal Hypertrophy Accompanied by Phosphoryation and Activation of AMPK-α1 Following Overload in LKB1 Knockout Mice. J Physiol. 2008 Mar 15;586(6):1731-41.

2007  Cuthbertson D.J., J. Babraj, G.P. Leese, K. Baar, K.J.W. Mustard, K. Smith, C. Sutherland, D.G. Hardie, and M.J. Rennie. AICAR acutely stimulates skeletal muscle glucose uptake in healthy men. Diabetes. 2007 Aug;56(8):2078-84.

2007  Timmons J.A., K. Wennmalm, O. Larsson, T.B. Walden, T. Lassmann, N. Petrovic, D.L. Hamilton, R.E. Gimeno, C. Wahlestedt, K. Baar, J. Nedergaard, and B. Cannon. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4401-6.

2007  Arruda E.M., K. Mundy, S. Calve,,and K. Baar. Denervation does not change the ratio of collagen I and collagen III mRNA in the extracellular matrix of muscle. Am J Physiol Endocrinol Metab. 2007 Feb;292(2):R983-7.

2006  Arruda EM, Calve S, Dennis RG, Mundy K, Baar K. Regional variation of tibialis anterior tendon mechanics is lost following denervation. J Appl Physiol. 2006 Oct;101(4):1113-7.

2006  Huang YC, Dennis RG, Baar K. Cultured slow vs. fast skeletal muscle cells differ in physiology and responsiveness to stimulation. Am J Physiol Cell Physiol. 2006 Jul;291(1):C11-7.

2005  Hecker, L., K. Baar, and K.N. Bitar. Development of a 3-Dimensional Physiological Model of the Internal Anal Sphincter Bioengineered in-vitro from Isolated Smooth Muscle Cells. Amer. J. Physiol.: Gastrointest Liver Physiol, 2005 Aug;289: G188-G196.

2005  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.

2005  Huang, Y-C, R.G. Dennis, and K. Baar. Rapid formation of functional muscle in vitro using fibrin gels. Feb 2005; 98: 706 - 713.

2004  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.

2003  Baar, K., Z. Song, C.F. Semenkovich, T.E. Jones, D.H. Han, L.A. Nolte, E.O. Ojuka, M. Chen, and J.O. Holloszy. Overexpression of nuclear respiratory factor 1 increases muscle glucose transport capacity. FASEB J. 2003 17(12): p. 1666-1673.

2002  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.

2002  Chen, Y.W., G. Nader, K. Baar, M. Fedele, E.P. Hoffman, and K.A. Esser. Response of muscle to acute resistance exercise defined by transcriptional and translational profiling. J. of Physiol. 2002 Nov 15;545(Pt 1):27-41.

2001  Baar, K., C. E. Torgan, W. E. Kraus, and K. A. Esser. Autocrine phosphorylation of the 70 KDa S6 protein kinase in response to acute stretch in C2C12 myotubes. Mol. Cell Biol. Res. Comm. 2001: 76-80.

1999  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.