Department of Biology

Joshua Meisel

Joshua MeiselAssistant Professor of Biology
Ting Tsung and Wei Fong Chao Endowed Chair in Neuroscience

Professor Meisel is a new faculty member. He will begin on July 1, 2024

Research Description

Mitochondrial genetics and metabolism in health and neurodegenerative disease

Mitochondria are the products of an ancient symbiosis wherein an archaeal cell engulfed a bacterium, giving rise to the “powerhouse” of the eukaryotic cell. Mutations in mitochondrial genes – encoded by both the nuclear and mitochondrial genomes – underlie common and rare neurodegenerative diseases for which we have no effective therapies. Our lab’s goal is to discover genetic and environmental suppressors of mitochondrial dysfunction to ultimately rescue mitochondrial disease.

My work has explored how hypoxia (low oxygen) can rescue multiple models of mitochondrial disease (e.g. Friedreich’s ataxia and Leigh Syndrome). Using forward genetic screens, we identified suppressor mutations that also rescue these mitochondrial defects, shedding light on the hypoxia rescue mechanism and identifying new genetic pathways with therapeutic potential. My lab at Brandeis will use C. elegans genetics, neurobiology, and biochemistry to investigate the mechanisms that govern mitochondrial adaptations to (1) variable metabolic demands across tissues and cell types, with a particular focus on the dopaminergic neurons, (2) mitochondrial dysfunction which occurs in rare disease or naturally as part of the aging process, and (3) changes in the environment, such as oxygen gradients experienced during development or in natural environments.

Selected Publications

  1. Meisel JD, Wiesenthal PP, Mootha VK*, and Ruvkun G*. (2024) Widespread activation of a neuron-specific mitochondrial complex I subunit by the RNA methyltransferase CMTR-1. Accepted at Current Biology.
  2. Meisel JD, Miranda M, Skinner OS, Wiesenthal PP, Wellner SM, Jourdain AA, Ruvkun G*, Mootha VK*. (2024) Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism. Cell 187(3): 659-675.
  3. Ast T*, Meisel JD*, Patra S, Wang H, Grange RMH, Kim SH, Calvo SE, Orefice LL, Nagashima F, Ichinose F, Zapol WM, Ruvkun G, Barondeau DP, Mootha VK. (2019) Hypoxia Rescues Frataxin Loss by Restoring Iron Sulfur Cluster Biogenesis. Cell 117(6): 1507-1521.
  4. Meisel JD and Kim DH. (2016) Inhibition of Lithium-Sensitive Phosphatase BPNT-1 Causes Selective Neuronal Dysfunction in C. elegans. Current Biology 26(14): 1922-8. [Featured on cover]
  5. Meisel JD, Panda O, Mahanti P, Schroeder FC, and Kim DH. (2014) Chemosensation of Bacterial Secondary Metabolites Modulates Neuroendocrine Signaling and Behavior of C. elegans. Cell 159(2): 267-80.
  6. Meisel JD and Kim DH. (2014) Behavioral avoidance of pathogenic bacteria by Caenorhabditis elegans. Trends in Immunology 35(10): 465-70.