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

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

Lasker Clinical Research Scholar and Investigator
Address
Inherited Movement Disorders Unit, Neurogenetics Branch (NGB)

BG 35 RM 2A-211
35 CONVENT DR
BETHESDA MD 20814

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 and the Movement Disorders fellowship at Penn Neurology in 2020. 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). He was awarded a Lasker Clinical Research Scholarship and became a tenure track investigator in 2020. In 2022, he was awarded the Grass Foundation - American Neurological Association Award in Neuroscience. His laboratory focuses on mitochondrial dysfunction and stress responses in neurodegeneration.

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Neurodegeneration is an increasing and unmitigated disease burden in our aging population. Among its causes are damaged mitochondria that accumulate with age, particularly in post-mitotic neurons and myocytes. Our group studies monogenic disorders to uncover mitochondrial stress responses that curb mitochondrial damage in neurodegeneration. Our focus includes PINK1 and Parkin, which form a stress-induced mitophagy pathway that targets damaged mitochondria for degradation. Mutations in these genes are the most common recessive forms of Parkinson’s disease, linking mitophagy to neurodegeneration. We are additionally focused on dominant mutations in the paralogs CHCHD2 and CHCHD10, which cause Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and myopathy. In addition to enabling precision therapies for neurogenetic disorders, our work is uncovering fundamental mitochondrial stress responses to mitochondrial damage.

  • Alexandra Jean (AJ) Gilsrud (post-bac)
  • Tzu-Hsiang (Eric) Huang, PhD (post-doc)
  • Xiaoping Huang, MD (lab manager, animal biologist)
  • Christian Lantz (PhD student)
  • Hsin-Pin Lin, MD, PhD (clinical fellow)
  • Mario Shammas (MD/PhD student)
  • Julia Thayer, PhD (post-doc)
  1. Shammas MK, Huang X, Wu BP, Fessler E, Song I, Randolph N, Li Y, Bleck CKE, Springer DA, Fratter C, Barbosa IA, Powers AF, Quirós PM, Lopez-Otin C, Jae LT, Poulton J, Narendra DP. OMA1 mediates local and global stress responses against protein misfolding in CHCHD10 mitochondrial myopathy. Journal of Clinical Investigation J Clin Invest. 2022 Jun 14:e157504. PMID: 35700042
  2. Zhu W, Huang X, Yoon E, Bandres-Ciga S, Blauwendraat C, Billingsley KJ, Cade JH, Wu BP, Williams VH, Schindler AB, Brooks J, Gibbs JR, Hernandez DG, Ehrlich D, Singleton AB, Narendra DP. Heterozygous PRKN mutations are common but do not increase the risk of Parkinson’s disease. Brain. 2022 Jun 30;145(6):2077-2091. PMID: 35640906
  3. Liu YT, Sliter DA, Shammas MK, Huang X, Wang C, Calvelli H, Maric DS, Narendra DP. Mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than mito-QC. Autophagy. 2021 Nov;17(11):3753-3762. PMID: 33685343.
  4. Isonaka R, Goldstein DS, Zhu W, Yoon E, Ehrlich D, Schindler AB, Kokkinis AD, Sabir MS, Scholz SW, Bandres-Ciga S, Blauwendraat C, Gonzalez-Alegre P, Lopez G, Sidransky E, Narendra DP. α-Synuclein Deposition in Sympathetic Nerve Fibers in Genetic Forms of Parkinson's Disease. Mov Disord. 2021 Oct;36(10):2346-2357. PMID: 34076298.
  5. Liu YT, Huang X, Nguyen D, Shammas MK, Wu BP, Dombi E, Springer DA, Poulton J, Sekine S, Narendra DP. Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations. Hum Mol Genet. 2020 Jun 3;29(9):1547-1567. PMID: 32338760.
  6. Narendra DP, Guillermier C, Gyngard F, Huang X, Ward ME, Steinhauser ML. Coupling APEX labeling to imaging mass spectrometry of single organelles reveals heterogeneity in lysosomal protein turnover. J Cell Biol. 2020 Jan 6;219(1):e201901097. PMID: 31719114.
  7. Narendra DP, Isonaka R, Nguyen D, Schindler AB, Kokkinis AD, Ehrlich D, Bardakjian TM, Goldstein DS, Liang TW, Gonzalez-Alegre P. Peripheral synucleinopathy in a DJ1 patient with Parkinson disease, cataracts, and hearing loss. Neurology. 2019 Jun 4;92(23):1113-1115. PubMed PMID: 31028127
  8. Huang X, Wu BP, Nguyen D, Liu YT, Marani M, Hench J, Bénit P, Kozjak-Pavlovic V, Rustin P, Frank S, Narendra DP. CHCHD2 accumulates in distressed mitochondria and facilitates oligomerization of CHCHD10. Hum Mol Genet. 2018 Nov 15;27(22):3881- 3900. PubMed PMID: 30084972

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