Research and Publications

LAB VISION:

We are interested in what occurs at a molecular level when neurons are in the earliest stages of neurodegenerative disease. In particular, we study the processes of early axon degeneration and synaptic dysfunction and loss, which occur before neurons die. Molecular pathways activated in these neurons, and their communication with nearby non-neuronal cells, promotes disease progression and ultimately disconnects regions of the brain and peripheral nervous system from one another. We are looking for the earliest events that signal disease states, and hope to find ways to reduce or prevent these processes from occurring.

Our work has extremely broad applications ranging from Chemotherapy-Induced Peripheral Neuropathy (a primarily sensory neuropathy), Amyotrophic Lateral Sclerosis (ALS, a motor neuron disease), spinal cord injury, and diabetic neuropathy, all the way to late-onset CNS dementias including Alzheimer’s Disease, Parkinson’s Disease, and Frontotemporal Dementia. As such, this work has received funding from numerous public and private sources including cancer research foundations, the Muscular Dystrophy Association, National Science Foundation, and the NIH/NINDS. 

Recent work had led us to investigate the role of the endolysosomal system in the development of both neurodegenerative diseases and neurodevelopmental disorders. Please stay tuned for results in this area!

MODEL SYSTEMS:

We take advantage of three systems in the lab: the fruit fly (Drosophila melanogaster) the mouse (Mus musculus), and human iPSC-derived neurons. Each has distinct advantages that enable our multi-system approach to be entirely complementary and will help drive new discoveries. Shown below are terminals of some of our favorite neurons: motor neurons responsible for body movement, and sensory terminals responsible for detecting touch and temperature.

Publications 

2024

Kimberly A Chapman*, Farid Ullah*, Zachary A Yahiku*, Sri Varsha Kodiparthi, Georgios Kellaris, Sandrina P Correia, Tommy Stödberg, Christalena Sofokleous, Nikolaos M Marinakis, Helena Fryssira, Eirini Tsoutsou, Jan Traeger-Synodinos, Andrea Accogli, Vincenzo Salpietro, Pasquale Striano, Seth I Berger, Kelvin W Pond, Suman Sirimulla, Erica E Davis#, Martha RC Bhattacharya#. Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome via alteration of metabolic signaling. Preprint (medRxiv). July 1, 2024. DOI: https://doi.org/10.1101/2024.06.27.24309417 . *indicates co-first authorship; #indicates co-corresponding authorship.

2023

Wright EB*, Larsen EG*, Coloma-Roessle, C, Hart HR, Bhattacharya MRC. (2023) Transmembrane protein 184B (TMEM184B) promotes expression of synaptic gene networks in the mouse hippocampus. BMC Genomics Sept 20; 84:559. Link to Paper

Bhattacharya MRC (2023). A nerve-wracking buzz: lessons from Drosophila models of peripheral neuropathy and axon degeneration. Front Aging Neurosci Aug 8;15:1166146. Link to Paper

2022

Cho TS*, Beigate E*, Klein NE*, Sweeney ST, Bhattacharya MRC (2022) The putative Drosophila TMEM184B ortholog Tmep ensures proper locomotion by restraining ectopic firing at the neuromuscular junction. Molecular Neurobiology. Link to paper. 

Larsen EG, Cho TS, McBride ML, Feng J, Manivannan B, Madura C, Klein NE, Wright EB, Garcia-Verdugo HD, Jarvis C, Khanna R, Hu H, Largent-Milnes TM, Bhattacharya MRC (2022). TMEM184B promotes pruriceptive neuron specification to facilitate itch sensitivity. PAIN. Link to paper.

  • This article was the Editor’s Featured article for this issue, and was featured in a video abstract, which you can watch at this link!
  • We have also filed a U.S. Patent on using TMEM184B to alleviate itch associated with IL-31 (which happens in eczema and asthma). Looking forward to seeing the impact of our discoveries!

2020

Bhattacharya MRC. (2020) A Chemotherapy-Induced Peripheral Neuropathy Model in Drosophila melanogaster. Methods Mol Biol. 2143:301-310. doi: 10.1007/978-1-0716-0585-1_22. PMID: 32524489

2019 and earlier

Bhattacharya MRC#, Geisler S, Pittman SK, Doan RA, Weihl CC, Milbrandt J, DiAntonio A. TMEM184b Promotes Axon Degeneration and Neuromuscular Junction Maintenance. J Neurosci. 2016 Apr 27;36(17):4681-9. PubMed PMID: 27122027; PubMed Central PMCID: PMC4846669.     #Martha is corresponding author as faculty @ STLCOP.

Bhattacharya MR, Gerdts J, Naylor SA, Royse EX, Ebstein SY, Sasaki Y, Milbrandt J, DiAntonio A. A model of toxic neuropathy in Drosophila reveals a role for MORN4 in promoting axonal degeneration. J Neurosci. 2012 Apr 11;32(15):5054-61. PubMed PMID: 22496551; PubMed Central PMCID: PMC3336743.

Bhattacharya MR, Bautista DM, Wu K, Haeberle H, Lumpkin EA, Julius D. Radial stretch reveals distinct populations of mechanosensitive mammalian somatosensory neurons. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):20015-20. PubMed PMID: 19060212; PubMed Central PMCID: PMC2604979.

Li R, Chase M, Jung SK, Smith PJ, Loeken MR. Hypoxic stress in diabetic pregnancy contributes to impaired embryo gene expression and defective development by inducing oxidative stress. Am J Physiol Endocrinol Metab. 2005 Oct;289(4):E591-9. PubMed PMID: 15928021.