Ji Li, Ph.D. Associate Research Scientist

B.S., Lanzhou University 1989; M.S., Lanzhou University 1992; Assistant Professor, Xiamen University 1994; Ph.D., Lanzhou University 1998; Associate Professor, Sichuan University 2000; Visiting Fellow, National Institute on Aging/NIH 2000; Postdoctoral Fellowship, Yale School of Medicine, 2002; Joined Yale Faculty 2004.

Research Interest:Cardiac Stress Signaling Pathways and the Biology of Aging

My research interest is in the altered adaptations to cellular stress that occur with aging. Although it is generally accepted that aging is associated with a decreased ability to cope with environmental stresses, there is little experimental evidence linking this decline in stress tolerance to alterations in specific pathways known to be involved in regulating stress responsiveness. We hypothesize that aging is associated with a decline in the ability of myocardial cells to activate host responses to hypoxic injury, and that this, in turn, might contribute to a reduced tolerance to ischemic insults in aged individuals with coronary artery disease. Alterations in AMP-activated protein kinase (AMPK) activity might potentially contribute to the decline in stress tolerance observed with aging. There is also significant evidence linking genetic mutations in the AMPK genes to abnormal function of cardiac and skeletal muscle. We are currently investigating the mechanisms leading to altered AMPK activation in response to ischemia/reperfusion with aging, and determining the effects of aging on the downstream effectors of AMPK in the ischemic heart. Our goal is to understand the mechanisms that underlie the reduced tolerance to ischemia/reperfusion stress seen in the elderly with the hope of devising novel strategies to prevent the decline, or to boost responsiveness in aged populations.


Li, J, Gorospe, M., Hutter, D., Barnes, J., Keyse, S.M., Liu, Y.: Transcriptional Induction of MKP-1 in Response to Stress is Associated with Histone H3 Phosphorylation/Acetylation. Mol Cell Biol 21:8213-8224, 2001.

Li, J., Sinogeeva, N., Chen, P., Barnes, J., Wersto, R.P., Chrest, F.J., Gorospe, M., Liu, Y.: Arsenic Trioxide Promotes Histone H3 Modification at the Chromatin of CASPASE-10 during Apoptosis of Acute Promyelocytic Leukemia Cells. J Biol Chem 277:49504-49510, 2002.

Cui, K., Li, J., Xing, G., Li, J.L., Wang, L., Wang, Y.: Effect of Hydrogen Peroxide on Synthesis of Proteins during Somatic Embryogenesis in Lycium Barbarum. Plant Cell, Tissue and Organ Culture 68: 187-193, 2002.

Hutter, D., Chen, P., Li, J., Barnes, J., Liu, Y.: The Carboxyl-terminal Domains of MKP-1 and MKP-2 Have Inhibitory Effects on Their Phosphatase Activity. Mol Cell Biochem 233: 107-117, 2002.

Chen, P., Li, J., Barnes, J., Kokkonen, G., Lee, J.C., Liu, Y.: Restraint of the Pro-inflammatory Cytokine Biosynthesis by MKP-1 in Lipopolysaccharide-stimulated Macrophages. J Immunol 169:6408-6416, 2002.

Li, J., Gorospe, M., Barnes, J., Liu, Y.: Tumor Promoter Arsenite Stimulates Histone H3 Phosphoacetylation of Proto-oncogenes c-fos and c-jun Chromatin in Human Diploid Fibroblasts. J Biol Chem 278:13183-13191, 2003.

Ikeyama, S., Wang, X.T., Li, J., Podlutsky, A., Martindale, J.L., Kokkonen, G., Van Huizen, R., Gorospe, M., Holbrook, N.J.: Expression of the Pro-apoptotic Gene gadd153/chop Is Elevated in Liver with Aging and Sensitizes Cells to Oxidant Injury. J Biol Chem 278: 16726-16731, 2003.

Li, J., Holbrook, N.J.: Common Mechanisms for Declines in Oxidative Stress Tolerance and Proliferation with Aging. Free Rad Biol Med 35:292-299, 2003.

Li, J., Holbrook, N.J.: Elevated of gadd153/chop Expression and Enhanced c-Jun N-terminal Protein Kinase Activation Sensitize Aged Cells to ER Stress. Exp. Gerontology 39:735-744, 2004.

Russell, R.R., Li, J., Coven, D.L., Pypaert, M., Zechner, C., Palmeri, M., Giordano, F.J., Mu, J., Birnbaum, M.J., Young, L.H.: AMP-activated Protein Kinase Mediates Ischemic Glucose Uptake and Prevents Post-ischemic Cardiac Dysfunction, Apoptosis and Injury. J. Clinical Investigation 114: 465-503, 2004.

Li, J., Hu, X., Selvakumar, P., Russell, R.R., Cushman, S.W., Holman, G.D., Young, L.H.: Role of the Nitric Oxide Pathway in AMPK-mediated Glucose Uptake and GLUT4 Translocation in Heart Muscle. American J. Physiology 287:E834-E841, 2004.

Baron, S*., Li, J*., Russell, R.R., Neumann, D., Miller, E.J., Tuerk, R., Walliman, T., Hurley, R., Witters, L.A., Young, L.H. (*The first two authors contributed equally). Dual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart. Circulation Research 96:337-345, 2005.

Young, L.H., Li, J., Baron, S.J., Russell, R.R.: AMP-activated Protein Kinase: A Key Stress Signaling Pathways in the Heart. Trends Cardiovasc Med 15:110-118, 2005.

Li, J., Miller, E.J., Ninomiya-Tsuji, J., Russell, R.R., Young, L.H.: AMP-activated Protein Kinase Activates p38 Mitogen-activated Protein Kinase by Increasing p38 MAPK Recruitment to TAB1 in the Ischemic Heart. Circulation Res. 97:872-879, 2005.

Miller, E.J., Russell, R.R., Li, J., Young, L.H.: AMPK-A Pivotal Rheostat in the Control of Cardiac Metabolism. Drug Discovery Today: Disease Mechanisms 2:93-100, 2005.

Li, J., Coven, D.L., Miller, E.J., Hu, X., Young, M.E., Carling, D., Sinusas, A., Young, L.H.: Activation of AMPK a- and g-isoform Complexes in the Intact Ischemic Rat Heart. Am J Physiol 291:H1927-H1934, 2006.

Shi, X., Leng, L., Wang, T., Wang, W., Du, X., Li, J., McDonald, C., Chen, Z., Murphy, J.W., Lolis, E., Noble, P., Knudson, W., Bucala, R.: CD44 is the signaling component of MIF CD74 receptor complex. Immunity 25:595-606, 2006.

Zhang, L., Li, J., Young, L.H., Caplan, M.J.: AMP-activated Protein Kinase Regulates the Assembly of Epithelial Tight Junctions. P Natl Acad Sci USA (PNAS) 103:17272-17277, 2006.

Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, Liu Z, Dong J, Mustard KJ, Hawley SA, Befroy D, Pypaert M, Hardie DG, Young LH and Shulman GI. Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell Metabolism 5:151-156, 2007.

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Last modified: Monday, 26-Feb-2007 08:52:47 EST (PL).