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Assistant Clinical Investigator

Derek Narendra, M.D., Ph.D.

Neurogenetics Branch


Building 35 Room 2A215
Convent Drive
Bethesda MD 20814
Office: 301-594-4737


derek.narendra@nih.gov

Dr. Narendra received his B.A. from Columbia University in 2002, Ph.D. from University of Cambridge in 2012, and M.D. from the University of Michigan in 2012. During his graduate research with mentors Dr. Richard Youle and Professor Sir John Walker, he identified a novel mitophagy pathway involving the coordinated activities of Parkin and PINK1, mutations in which are the leading cause of Early Onset Parkinson’s Disease. He completed the Brigham and Women’s Hospital & Massachusetts General Hospital Harvard Neurology Residency Program in 2016 with additional fellowship training in movement disorders at the University of Pennsylvania. In 2017, Dr. Narendra received the McFarland Transition to Independence Award for Neurologist-Scientists and joined the NINDS as an Assistant Clinical Investigator within the Neurogenetics Branch (NINDS). His laboratory focuses on the molecular pathogenesis of Early Onset Parkinson’s Disease.



Our group studies inherited movement disorders with a focus on the genetics and molecular pathogenesis of Early Onset Parkinson’s Disease (EOPD) (onset at 50 years or before). Whereas idiopathic Parkinson’s disease is typically sporadic, EOPD is frequently caused by mutation(s) in a single gene. Many of the genes responsible for EOPD have been identified. The relationship among these genes in the molecular pathogenesis of Parkinson’s disease, however, remains ill-defined. We recently discovered that two of these genes, Parkin and PINK1, function in a novel mitochondrial quality control pathway in which impaired mitochondria are targeted for lysosomal degradation by mitophagy (a selective form of macroautophagy). Interestingly, two other genes causing EOPD, DJ-1 and the recently identified CHCHD2, share with Parkin and PINK1 a role in mitochondrial biology, suggesting commonalities in pathogenesis. To characterize the molecular pathogenesis of EOPD, we use a combination of novel genetic tools, advanced imaging methods like super-resolution microscopy, quantitative proteomics, and biochemical studies in cellular and mouse models. Additionally, we are collecting DNA samples and fibroblasts from patients with EOPD to better assess the contribution of known genes to the risk of EOPD and to uncover new causes of EOPD, using exome sequencing. It is our hope that these studies will ultimately clarify the molecular pathogenesis of Parkinson’s disease and guide the development of disease-modifying therapy.

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  • Xiaoping Huang, M.D.
    Animal Biologist

  • Yi-Ting Liu, B.A.
    Post baccalaureate IRTA Fellow

  • Melika Marani
    Summer Student

  • Diana Nguyen, B.S.
    Post baccalaureate UGSP Fellow

  • Beverly Wu, B.S.
    Post baccalaureate UGSP Fellow

  • 1) Narendra DP (2016)
  • PARKIN/PINK1 Pathway for the Selective Isolation and Degradation of Impaired Mitochondria. Chapter in book: Mitochondrial Mechanisms of Degeneration and Repair in Parkinson’s Disease (Springer)
  • 2) Lazarou M*, Narendra DP*, Jin SM, Tekle E, Banerjee S, Youle RJ (2013)
  • PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding
  • J Cell Biol, 200(2), 163-72. *equal author contribution
  • 3) Narendra DP, Wang C, Youle RJ, Walker JE (2013)
  • PINK1 rendered temperature sensitive by disease-associated and engineered mutations
  • Hum Mol Genet, 22(13), 2572-89
  • 4) Narendra DP, Youle RJ (2012)
  • Neurodegeneration: Trouble in the cell's powerhouse
  • Nature, 483(7390), 418-9
  • 5) Narendra D, Walker JE, Youle R (2012)
  • Mitochondrial quality control mediated by PINK1 and Parkin: links to parkinsonism
  • Cold Spring Harb Perspect Biol, 4(11)
  • 6) Youle RJ, Narendra DP (2011)
  • Mechanisms of mitophagy
  • Nat Rev Mol Cell Biol, 12(1), 9-14
  • 7) Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ (2010)
  • PINK1 is selectively stabilized on impaired mitochondria to activate Parkin
  • PLoS Biol, 8(1)
  • 8) Narendra D, Kane LA, Hauser DN, Fearnley IM, Youle RJ (2010)
  • p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both
  • Autophagy, 16;6(8), 1090-106
  • 9) Narendra D, Tanaka A, Suen DF, Youle RJ (2008)
  • Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
  • J Cell Biol, 183(5), 795-803
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