- BA: Indiana University, Bloomington, IN
- PhD: Massachusetts Institute of Technology, Cambridge, MA
- Postdoctoral training: Harvard Medical School, Boston, MA
The long-term goal of research in my laboratory is to define novel target molecules and pathways for safe and effective modulation of autophagy as a treatment against neurodegeneration induced by both acute (trauma) and chronic (neurodegenerative diseases) causes.
Autophagy is a catabolic process mediating the turnover of bulk cytoplasmic constituents including organelles and protein aggregates in a lysosome-dependent manner. It is necessary for cellular homeostasis and protects organisms from a variety of diseases, including neurodegeneration and aging. Up-regulation of autophagy has been observed following traumatic brain injury (TBI) and spinal cord injury (SCI), but its mechanisms and unction in those contexts remain unknown. We use in vivo and in vitro models to examine the role of autophagy after TBI and SCI, and to delineate the molecular mechanisms involved. Our data demonstrate that although autophagosomes accumulate in the brain and spinal cord after TBI and SCI, respectively, autophagic degradation cannot proceed to completion. This block of autophagy is especially apparent in neurons and correlates with markers of neuronal cell death. Thus defective autophagy may contribute to neuronal cell death in TBI and SCI. We are currently investigating potential methods to re-activate autophagy flux as a treatment for TBI and SCI.
Additionally, we are using in vitro models, including human induced pluripotent stem (iPS) cells, to examine function and mechanisms of USP24, a novel gene associated with Parkinson’s disease (PD). Our data demonstrate that USP24 is a negative regulator of autophagy and its inactivation can be beneficial in cellular models of PD. We are investigating whether inactivation of USP24 may be a potential future target for treatment of PD and other neurodegenerative conditions, including TBI and SCI.
- Py, B.F., Desai, B.N., Jin, M., Penumaka, A., Zhu, H., Kober, M., Dietrich, A., Lipinski, M.M., Henry, T., Clapham, D.E. and Yuan, J. (2014) Caspase-11 controls interleukin-1β release through degradation of TRPC1. Cell Reports, accepted
- Zhao, Z., Faden, A., Loane, D., Lipinski, M., Sabirzhanov, B. and Stoica, B. (2013) Neuroprotective effects of geranylgeranylacetone in experimental traumatic brain injury. J Cereb Blood Flow Metab, 33:1897-908
- Xu Y., Yuan J. and Lipinski M. M. (2013) Live imaging and single cell analysis reveal differential dynamics of autophagy and apoptosis. Autophagy, 9:1418-30
- Ofengeim D., Shi P., Miao B., Xia X., Fan Y., Lipinski M.M., Yuan J., Wong S.T.C. and Degterev A. (2012) Identification of small molecule inhibitors of neurite loss induced by A peptide using high-content screening. J Biol Chem, 287:8714-23
- 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 Sci Syst Appl Workshop, Apr 1 2009:128
- 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 monocytogenes intracellular growth in the early phase of primary infection. Autophagy, 3:117-125
- 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 & 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” edited by Reed J.C. and Green D.R., Cambridge University Press, 2011
- 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. Curr Opin Pharmacol, 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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