Overview

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. In neurons, this block of autophagy is caused by phospholipase-mediated lysosomal membrane damage and contributes to neuronal cell death. Inhibition of autophagy is also observed in activated microglia and infiltrating macrophages and may contribute to neuroinflammation.

We are currently investigating the effects of TBI-induced perturbation in  brain  lipid homeostasis  on microglial and  macrophage autophagy  and assessing the contribution of the autophagy-lysosomal pathway to delayed development of neurodegeneration and dementia after TBI. Additionally, we are using in vitro models, including human induced pluripotent stem (iPS) cells,to examine the 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.

 Former lab members:

• Nivedita Hegdekar, PhD, Graduate Student 2014-2021; Postdoctoral Fellow 2022-2023
  Current position: Strategy Consultant, Life Sciences

• Harry Choi, PhD, Postdoctoral Fellow, 2017-2022 

• Julia Thayer, PhD, Graduate Student 2015-2019; Postdoctoral Fellow 2019-2020
  Current position: Postdoctoral Fellow, NIH, Bethesda, MD

• Shuo Liu, MD-PhD, Postdoctoral Fellow 2012-2017
  Current position: Resident in Pathology, University of South Alabama, Mobile, AL

• Deepika Philkana, MS, Graduate Student 2015-2016
  Current position: Research Associate-II Sera Care Life Sciences, Gaithersburg, MD

• Prarthana Ravishankar, MS, Graduate Student 2014-2015
  Current position: Special Project Associate, Mayo Clinic, Jacksonville, FL

• Joshua Ostovitz, MS, Graduate Student 2018-2019
  Current position: Research Technician, Center for Translational Research In Imaging, UMB-SOM, Baltimore MD

Collaborators at University of Maryland:

• Junfang Wu (UMB-SOM, Anesthesiology/STAR)
• Alan Faden, MD (UMB-SOM, Anesthesiology/STAR)
• Eugene Koh (UMB-SOM, Orthopedics)
• Ricardo Feldman, PhD (UMB-SOM, Microbiology & Immunology)
• Ola Awad, PhD (UMB-SOM, Microbiology & Immunology)
• Maureen Kane, PhD (UMB School of Pharmacy)
• Jace Jones, PhD (UMB School of Pharmacy)
• Michael Cummings, PhD (UMCP)

Publications

Please see Dr. Lipinski's faculty profile for a complete list of her publications.

You can also see his publications on PubMed.

Contact

Email: Mlipinski@som.umaryland.edu
Phone: (410) 706-5187