Department of Neurobiology, Physiology and Behavior
Department of Physiology and Membrane Biology, School of Medicine
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
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.
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.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Biomedical Engineering Graduate Group
- Molecular, Cellular and Integrative Physiology
Specialties / Focus
- Cellular Physiology
- Developmental Biology
- Exercise Physiology
- Gene Regulation
- Molecular Physiology
- Molecular Physiology
- Muscular and Skeletal Physiology
- Signal Transduction
- Functional Molecular Biology Lab
- Dana Lis
- Alec Avey
- Jacinda Tran
- 2000 PhD (Physiology and Biophysics) University of Illinois
- 1994 MA (Human Biodynamics) University of California, Berkeley
- 1992 BS (Kinesiology) University of Michigan
Roberts, M.A., M.A. Wallace, A.A. Tomilov, Z. Zhou, G.R. Marcotte, D. Tran, G. Perez, E. Gutierrez-Casado, S. Koike, T.A. Knotts, D.M. Imai, S.M. Griffey, K. Kim, K. Hagopian, F.G. Haj, K. Baar, G.A. Cortopassi, J.J. Ramsey, and J.A. Lopez-Dominguez. A ketogenic diet extends longevity and healthspan in adult mice. Cell Metabolism 2017 Volume 26, Issue 3, p539–546.
Park, S.J., O. Gavrilova, A.L. Brown, J.E. Soto, S. Bremner, J. Kim, X. Xu, S. Yang, J.H. Um, L.G. Koch, S.L. Britton, R.L. Lieber, A. Philp, K. Baar, S.G. Kohama, E.D. Abel, M.K. Kim, and J.H. Chung. DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging. Cell Metabolism. 2017 May 2;25(5):1135-1146
Hughes D.C., G.R. Marcotte, A.G. Marshall, D.W. West, L.M. Baehr, M.A. Wallace, P.M. Saleh, S.C. Bodine, and K Baar Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability. J Gerontol A Biol Sci Med Sci. 2017 May 1;72(5):640-648.
Shaw, G., A. Lee-Barthel, M.L. Ross, B. Wang, and K. Baar. Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis. Am J Clin Nutr. 2017 Jan;105(1):136-143.
Lee, C.A., A. Lee-Barthel, L. Marquino, N. Sandoval, G. Marcotte, and K. Baar. Estrogen inhibits lysyl oxidase and decreases mechanical function in engineered ligaments. J. Appl. Physiol. 2 April 2015 May 15;118(10):1250-7.
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.
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.
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.