Shock,Trauma and Anesthesiology Research (STAR) Center; Center for Stem Cell Biology and Regenerative Medicine; Center for Biomolecular Therapeutics
Education and Training
- BA: Indiana University, Bloomington, IN
- PhD: Massachusetts Institute of Technology, Cambridge, MA
- Postdoctoral training: Harvard Medical School, Boston, MA
Additional Affiliations at UMB
- Member, Shock, Trauma and Anesthesiology Research (STAR) Center
- Member & Neural Stem Cell Interest Group Leader, Center for Stem Cell Biology and Regenerative Medicine
- Member, Center for Biomolecular Therapeutics
Autophagy, Neurodegeneration, Traumatic Brain Injury, Spinal Cord Injury, Parkinson's Disease
Selected Recent Publications
Sarkar C, Jones JW, Hegdekar N, Thayer JA, Kumar A, Faden AI, Kane MA, Lipinski MM. PLA2G4A/cPLA2-mediated lysosomal membrane damage leads to inhibition of autophagy and neurodegeneration after brain trauma. Autophagy. 2019; Jun 25:1-20. PMID: 31238788.
Thayer JA, Awad O, Hegdekar N, Sarkar C, Tesfay H, Burt C, Zeng X, Feldman RA, Lipinski MM. The PARK10 gene USP24 is a negative regulator of autophagy and ULK1 protein stability. Autophagy. 2019; Apr 7:1-14. PMID: 30957634
Li Y, Jones JW, M C Choi H, Sarkar C, Kane MA, Koh EY, Lipinski MM#, Wu J#. cPLA2 activation contributes to lysosomal defects leading to impairment of autophagy after spinal cord injury. Cell Death Dis. 2019; Jul 11;10(7):531. PMID:31296844
Liu S, Li Y, Choi HMC, Sarkar C, Koh EY, Wu J# and Lipinski MM#. Lysosomal damage after spinal cord injury causes accumulation of RIPK1 and RIPK3 proteins and potentiation of necroptosis. Cell Death & Disease. 2018; 9:476. PMID: 29686269
Barekat A, Gonzalez A, Mauntz R, Kotzebue R, Molina B, El-Mecharrafie N, Conner C, Garza S, Melkani G, Joiner W, Lipinski M, Finley K and Ratliff E. Using Drosophila as an integrated model to study mild repetitive traumatic brain injury. Scientific Reports. 2016; 6:25252. PMID: 27143646.
Liu S, Sarkar C, Dinizo M, Faden AI, Koh EY, Lipinski MM#, Wu J#. Disrupted Autophagy After Spinal Cord Injury is Associated With ER Stress and Neuronal Cell Death. Cell Death & Disease. 2015; 6:e1582. PMID: 25569099.
Srakar C, Zhao Z, Aungst S, Sabirzhanov B, Faden AI, and Lipinski MM. Impaired Autophagy Flux is Associated With Neuronal Cell Death After TBI. Autophagy. 2014; 10(12):1418-30. PMID: 25484084.
Other Highlighted Publications
Lipinski MM, Zheng B, Lu T, Yan Z, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR, Yuan J. A Genome-wide Analysis Reveals Mechanisms Modulating Autophagy in Normal Brain Aging and in Alzheimer's Disease. PNAS. 2010;107(32):14164-9. PMID: 20660724.
Lipinski MM, Hoffman G, Ng A, Zhou W, Py BF, Hsu E, Liu X, Eisenberg J, Liu J, Blenis J, Xavier RJ, A Genome-wide SiRNA Screen Reveals Multiple MTORC1 Independent Signaling Pathways Regulating Autophagy Under Normal Nutritional Conditions. Developmental Cell. 2010; 18(6):1041-52. PMID: 20627085.
Complete List of Published Work:
Function and Mechanisms of Autophagy in Neurotrauma & Neurodegeneration
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. Accumulation of autophagosomes has been observed following traumatic brain injury (TBI) and spinal cord injury (SCI), but its mechanisms and function 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 long-term goal 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.
Mechanisms and consequences of autophagy dysfunction after traumatic brain injury: We are using transgenic mice and in vitro models to determine the mechanisms leading to lysosomal damage and disruption of autophagy flux following traumatic brain injury (TBI). Specifically, we are focusing on the function of cellular phospholipase cPLA2 in mediation of lysosomal membrane damage after TBI. We are also investigating the effects of inhibition of autophagy on neuronal cell death and neuroinflammation after TBI as well as testing whether restoration of autophagy can be used as a treatment to improve functional outcomes after brain trauma.
Effects of autophagy disruption on neuronal cell death and functional recovery after spinal cord injury: In collaboration with Dr. Junfang Wu (Anesthesiology) and Dr. Eugene Koh (Orthopaedics) we are using transgenic mouse mice and in vitro models to determine the influence of disruption of lysosomal function and autophagy flux on apoptotic and non-apoptotic neuronal cell death mechanisms following spinal cord injury (SCI). We are also investigating potential involvement of inhibition of autophagy in axonal damage observed after SCI. Furthermore we are testing whether enhancing autophagy may have beneficial effects on functional outcomes after SCI.
Mechanisms of the PARK10 gene USP24 in regulation of autophagy: USP24 is a gene located in the PARK10 locus associated with late onset Parkinson's disease. We identified USP24 as a novel negative regulator of autophagy and are using cell-based models including human iPS cells differentiated into dopaminergic neurons to investigate its function and mechanisms. We are also investigating whether inactivation of USP24 may be a potential future target for treatment of PD and other neurodegenerative conditions. The iPSC modeling is carried out in collaboration with Drs. Ricardo Feldman and Ola Awad (Microbiology & Immunology).
Active Grant Support:
- The Function and Mechanisms of Autophagy in Spinal Cord Injury
NIH R01 NS094527 (PI: Junfang Wu)
06/01/2016 – 05/31/2021
- Function and Mechanisms of Autophagy-lysosomal Pathway in Traumatic Brain Injury
NIH R01 NS091218 (PI: Marta Lipinski)
03/01/2015 – 02/29/2020
- Inhibition of the PARK10 Gene USP24 as a Neuroprotective Treatment in Parkinson’s Disease
Maryland Stem Cell Research Fund 2019-MSCRFE-5106 (PI: Marta Lipinski)
07/01/2019 - 06/30/2021
- Member, Society for Neuroscience
- Member & Council Member, National Neurotrauma Society
- Member, American Society for Cell Biology
Current Lab Members
- Chinmoy Sarkar, PhD, Research Associate
- Harry Choi, PhD, Postdoctoral Fellow
- Julia Peter, Graduate Student (PhD Program in Toxicology)
- Nivedita Hegdekar, Graduate Student (PhD Program in Biochemistry)
From left: Shuo Liu, Niv Hegdekar, Marta Lipinski, Julia Peter and Chinmoy Sarkar
Former Lab Members
Shuo Liu, MD-PhD, Postdoctoral Fellow, 2012-2017
Current Position: Resident in Pathology, University of South Alabama, Mobile, AL
- Deepika Philkana, MS, Student, Cellular and Molecular Biomedical Science Masters Program, 2015-2016
- Current position: Research Associate-II, Sera Care Life Sciences, Gaithesburg, MD
- Prarthana Ravishankar, MS, Student, Cellular and Molecular Biomedical Science Masters Program, 2014-2015
- Current position: Associate Scientist-II, Thermo Fisher Scientific, Frederick MD
- Josh Ostovitz, Graduate Student, MS, Student, Cellular & Molecular Biomedical Science Masters Program, 2017-2019
- Current position: Research Technician, Center for Translational Research In Imaging, University of Maryland School of Medicine, Baltimore, MD
Collaborators at UMB
- Junfang Wu, MD-PhD, Departament of Anesthesiology & Shock, Trauma and Anesthesiology Research (STAR) Center
- Eugene Koh, MD-PhD, Departmetn of Orthopaedics
- Ricardo Feldman, PhD, Department of Microbiology & Immunology
- Ola Awad, PhD, Department of Microbiology & Immunology
- Maureen A. Kane, PhD, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy
- Jace W. Jones, PhD, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy
Collaborators Outside UMB
- Kim Finley, PhD, San Diego State University, San Diego, CA
- Xianmin Zeng, PhD, Buck Institute for Research on Aging, Novato, CA