Brian Kennedy

Affiliations

Distinguished Professor, Department of Biochemistry and Physiology, Yong Loo Lin School of Medicine, NUS, Singapore. Director of National University Health System (NUHS) Centre for Healthy Ageing, Singapore. Professor, Buck Institute for Research on Ageing, Novato, CA, USA. Adjunct Professor, Leonard Davis School of Gerontology, USC, Los Angeles, CA, USA. Affiliate Faculty, Department of Biochemistry, University of Washington, Seattle, WA USA.

Education

• B.A. in Biochemistry and Mathematics, Northwestern University , Evanston , IL, USA 1985-1989
• Ph.D. in Biology , Massachusetts Institute of Technology, Cambridge, MA, USA 1990-1996

Companies

• Director, Centre for Healthy Ageing; Professor, Departments of Biochemistry and Physiology National University of Singapore (2017)
• Professor, Departments of Biochemistry and Physiology NUS Yong Loo Lin School of Medicine (2017)
• Adjunct Professor USC Davis School of Gerontology (2013)
• Professor Buck Institute for Research on Aging (2010)
• Affiliate Professor University of Washington (2010)
• President and CEO Buck Institute for Research on Aging (2010 — 2016)
• Visiting Professor in Aging Research Guangdong Medical College (2009 — 2014)
• Associate Professor University of Washington (2007 — 2010)
• Assistant Professor University of Washington (2001 — 2007)

Research Interest

Research in the Kennedy lab is directed at understanding the biology of ageing and translating research discoveries into new ways of delaying, detecting, preventing and treating human ageing and associated diseases.

Current Research Projects

Several research strategies are employed to understand the biology of human ageing and to develop translational approaches. We use multiple model organisms and systems for these purposes, relying on non-vertebrates for discovery-based approaches to generate hypotheses regarding ageing mechanisms and studies in mammals to test hypotheses and to develop translational strategies. Specific projects include:

Systems biology strategies to understand ageing – Using the yeast Saccharomyces cerevisiae, we employ large-scale genetic and molecular approaches to define how pathways controlling ageing interact in a network. Recently, we published a full genome analysis of replicative ageing, the number of divisions one yeast mother cell can undergo. Surprisingly, it is relatively easy to extend replicative lifespan, as nearly 250 long-lived gene deletions were identified. Currently, we are generating an epistasis network to define how these genes interact, and combining this with detailed analysis of specific long-lived mutants. In addition, we have identified drugs that extend yeast lifespan and seek their mechanism of action. We are also active with the nematode C. elegans, using it primarily as a short-lived multicellular species in which to define which yeast ageing pathways are conserved.

Murine longevity and studies and disease models – Several approaches are employed to identify the mechanisms governing mammalian ageing. Primary focus is on the mTOR pathway, which is intimately linked to ageing. Reduced mTOR signalling, for instance by treatment with rapamycin, extends both lifespan and healthspan, the disease-free and functional period of life. We use genetic and pharmacologic strategies to modify mTOR activity, with the goal of determining in which tissues mTOR modulates ageing, the temporal nature of interventions and, importantly, the pathways downstream of mTOR that transmit age-related signals. Other lines of experimental investigation are aimed at understanding BCAA metabolism and disease and understanding how altered nuclear lamin function is linked to ageing and diseases.

Selected Publications

• Liao, C.-Y., Anderson, S.S., Chicoine, N.H., Mayfield, J.R., Academia, E.C., Wilson, J.A., Pongkietisak, C., Thompson, M.A., Lagmay, E.P., Miller D.M., Hsu, Y.-M. McCormick, M.A., O’Leary, M.N., and Kennedy, B.K. 2016. Rapamycin reverses metabolic deficits in lamin A/C-deficient mice. Cell Rep. 17: 2542-2552. PMID: 27926859.
• Davis, S.S., O’Leary, M.N., Gutierrez, M.A., Nguyen, S.M., Mateen, S., Hsu, Y., Mitchell, K.P., Lopez, A.J., Vockley, G., Kennedy, B.K., and Ramanathan, A. 2016. Metformin inhibits branched chain amino acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD. Sci. Rep. 6: 28755. PMID: 27373929.
• Tsai, S., Rodriguez, A.A., Dastidar, S.G., Del Greco, E., Carr, K.L., Sitzmann, J.M., Academia, E.C., Viray, C.M., Martinez, L.L., Kaplowitz, B.S., Ashe, T.D., La Spada, A., and Kennedy, B.K. 2016. Increased 4E-BP1 expression protects against diet-induced obesity and insulin resistance in male mice. Cell Rep. 16: 1903-1914. PMID: 27498874.
• Moskalev, A., Chernyagina, E., Tsvetkov, V., Fedintsev, A., Shaposhnikov, M., Krut’ko, V., Zhavoronkov, A. and Kennedy, B.K. 2016. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell, 15: 407-415. PMID: 26970234.
• McCormick, M.A., Delaney, J.R., Tsuchiya, M., Tsuchiyama, S., Shemorry, A., Sim, S., Chou, A.C.-Z., Ahmed, U., Carr, D., Murakami, C.J., Schleit, J., Sutphin, G.L., Wasko, B.M., Bennett, C.F., Wang, A.M., Olsen, B., Beyer, R.P., Bammler, T.K., Prunkard, D., Johnson, S.C., Pennypacker, J.K., An, E., Anies, A., Castanza, A.S., Choi, E., Dang, N., Enerio, S., Fletcher, M., Fox, L., Goswami, S., Higgins, S.A., Holmberg, M.A., Hu, D., Hui, J., Jelic, M., Jeong, K.-S., Johnston, E., Kerr, E.O., Kim, D., Kim, J., Kirkland, K., Klum, S., Kotireddy, S., Liao, E., Lim, M., Lin, M.S., Lo, W.C., Lockshon, D., Miller, H.A., Moller, R.M., Muller, B., Oakes, J., Pak, D.N., Peng, Z.J., Pham, K.M., Pollard, T.G., Pradeep, P., Pruett, D., Rai, D., Robison, B., Rodriguez, A.A., Ros, B., Sage, M., Singh, M.K., Smith, E.D., Snead, K., Solanky, A., Spector, B.L., Steffen, K.K., Tchao, B.N., Ting, M.K., Vander Wende, H., Wang, D., Welton, K.L., Westman, E.A., Brem, R.B., Liu, X.-G., Suh, Y., Zhou, Z., Kaeberlein, M. and Kennedy, B.K. 2015. A comprehensive analysis of replicative lifespan in 4,698 single-gene deletion strains uncovers novel mechanisms of aging. Cell. Metab. 22: 895-906. PMID: 26456335.
• Tsai, S., Sitzmann, J.M., Dastidar, S.G., Rodriguez, A.A., Vu, S.L., McDonald, C.E., Academia, E.C., O’Leary, M.N., Ashe, T.D., La Spada, A.R. and Kennedy B.K. 2015. Activated muscle 4E-BP1 signaling improves metabolic parameters during aging and obesity. J. Clin. Invest. 125: 2952-2964. PMID: 26121750.
• Broadhurst, S., Choi, I.Y., Wei, M., Cheng, C.W., Sedrakyan, S., Navarrete, G., Dubeau, L., Yap, L.P., Park, R., Vinciguerra, M., Di Biase, S., Mirzaei, H., Mirisola, M.G., Childress, P., Ji, L., Groshen, S., Penna, F., Odetti, P., Perin, L., Conti, P.S., Ikeno, Y., Kennedy, B.K., Cohen, P., Morgan, T.E., Dorff, T.B. and Longo, V.D. 2015. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metab. 22: 86-99. PMID: 26094889.
• Schreiber, K.H., Ortiz, D., Academia, E.C., Anies, A.C., Liao, C.-Y. and Kennedy, B.K. 2015. Rapamycin-mediated mTORC2 inhibition is determined by the relative expression of FK506 binding proteins. Aging Cell, 14: 265-273. PMID: 25652038.
• He, C., Tsuchiyama, S.K., Nguyen, Q.T., Plyusnina, E.N., Terrill, S.R., Sahibzada, S., Patel, B., Faulkner, A.R., Shaposhnikov, M.V., Tian, R., Tsuchiya, M., Kaeberlein, M. Moskalev, A.A., Kennedy, B.K. and Polymenis, M. 2014. Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import. PLoS Genet. E1004860. PMID: 25521617.
• Kennedy, B.K., Berger, S.L., Brunet, A., Campisi, J., Cuervo, A.M., Epel, E.S., Franceschi, C., Lithgow, G.J., Morimoto, R.I., Pessin, J.E., Rando, T.A., Richardson, A., Schadt, E.E., Wyss-Coray, T., and Sierra, F. 2014. Geroscience: linking aging to chronic disease. Cell, 159: 709-713. PMID: 25417146.