Research Interests:Autophagy, a catabolic process mediating the turnover of bulk cytoplasmic constituents including organelles and protein aggregates in a lysosome-dependent manner, protects organisms from a variety of diseases, including neurodegeneration, cancer and aging. Up-regulation of autophagy has also been observed following traumatic brain injury (TBI), but its function in this context remains unknown. The goal of my research is use in vivo and in vitro models to examine the role of autophagy aftertraumatic injury, and to delineate the molecular mechanisms involved. Since mitochondrial damage plays an important role in neurodegenerationassociated with both TBI and Parkinson’s disease (PD), and prior head injury is a well-established epidemiological factor for PD, I will examine in TBI models the potential role of genes known to be involved in the regulation of mitochondrial autophagy (mitophagy) in PD. The long-term goal is to define novel druggable target molecules and pathways for theeffective modulation of autophagy in TBI and other neurodegenerative diseases.
Lipinski M.M., Zheng B., Py B.F., Lu T., Yan Z., Ng A., Xavier, R.J., Li C., Yankner B.A., Scherzer C.R. and Yuan J. (2010) A genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. PNAS, 107:14164-9
Lipinski M.M., Hoffman G., Ng A., Zhou W., Py B.F., Hsu E., Liu X., Eisenberg J., Liu J., Blenis J., Xavier R.J. and Yuan J. (2010) Multiple mTORC1 independent signaling pathways regulate autophagy through type III PI3 kinase under normal nutritional conditions. Dev. Cell, 18:1041-1052
Huang Y, Zhou X, Miao B, Lipinski M, Zhang Y, Li F, Degterev A, Yuan J, Hu G, Wong ST. (2010) A computational framework for studying neuron morphology from in vitro high content neuron-based screening. J Neurosci Methods, 190:299-309
Furuya, T., Kim, M., Lipinski, M., Li, J., Kim, D., Lu, T., Shen, Y., Rameh, L., Yankner, B.,Tsai, L. and Yuan, J. (2010) Negative regulation of Vps34 by Cdk mediated phosphorylation. Mol. Cell, 38:500-511
Huang Y, Zhou X, Miao B, Lipinski M, Xia Z, Hu G, Degterev A, Yuan J, Wong ST. (2009) An Image Based System Biology Approach for Alzheimer's Disease Pathway Analysis. IEEE NIH Life SciSystAppl Workshop, Apr 1 2009:128-132
Zhang Y., Zhou, X., Degterev, A., Lipinski, M., Adjeroh, D., Yuan, J. and Wong, S.T.C. (2007) Automated neurite extraction using dynamic programming for high-throughput screening of neuron-based assays. NeuroImage, 35:1502-15
Py, B.F.*, Lipinski, M.M.* and Yuan, J. (2007) Autophagy limits Listeria monocytogenesintracellular growth in the early phase of primary infection. Autophagy, 3:117-125 *first co-authors
Zhang Y., Zhou X., Degterev A., Lipinski M., Adjeroh D., Yuan J and Wong S.T. (2007) A novel tracing algorithm for high throughput imaging Screening of neuron-based assays. J Neurosci Methods, 160:149-62
Lipinski, M.M., MacLeod, K.F., Williams, B.O., Mullaney, T.L., Crowley, D. and Jacks, T. (2001) Cell-autonomous and non-cell-autonomous functions of the Rb tumor suppressor in CNS development. EMBO J. 20:3402-13
Reviews, commentaries and book chapters
Kepp O., Galluzzi L., Lipinski M., Yuan J. and Kroemer G. (2011) Cell death assays for drug discovery. Nat Rev Drug Discov, 10:221-37
Boyce M., Lipinski M.M., Py B.F. and Yuan J. Endoplasmic reticulum stress response in cell death and cell survival; in: “Apoptosis: Physiology and Pathology of Cell Death” edited by Reed JC and Green DR, New York: Cambridge University Press. In press.
Lipinski M.M. (2010) Towards the global understanding of the autophagy regulatory network. Autophagy, 6:1218-1220
Lipinski, M.M. and Yuan, J. (2005) A cellular response to an internal energy crisis. Cell, 123:3-5
Lipinski, M.M. and Yuan, J. (2004) Mechanisms of cell death in polyglutamine expansion diseases. CurrOpinPharmacol, 4:85-90
Yuan, J., Lipinski, M. and Degterev, A. (2003) Diversity in the mechanisms of neuronal cell death. Neuron, 40:401-413
Lipinski, M.M. and Jacks, T. (1999) The retinoblastoma gene family in differentiation and development. Oncogene, 18:7873-7882
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