Debomoy K. Lahiri, Ph.D.
Professor of Psychiatry
PhD, Banaras Hindu University (1980)
Neurobiology of Alzheimer’s disease: From Mechanistic Studies to Drug Target Discovery.
Research in my laboratory aims to understand cellular, genetic and molecular pathways of neurodegenerative diseases (e.g. Alzheimer’s disease-AD) and neurodevelopmental disorders (e.g., Autism, Fragile X). Particularly, we study the neurobiological function of synaptic proteins, the β-amyloid precursor protein (APP) and its metabolites, and other AD-related proteins. We have recently shown the novel role of specific microRNA species in the expression of APP and beta-secretase using human primary neuronal cultures and human brain tissues. Further, our group has shown neuroprotective effects of dietary nutrients, such as S-Ally cysteine (SAC) and nanoparticle emulsified curcumin. We are also investigating novel functions of some established therapeutic agents, such as acamprosate, memantine, rivastigmine and SSRIs as well as novel strategies such as phytochemicals, immunotherapy, and electromagnetic field stimulation.
In short, the following projects are among those underway in our laboratory: 1) to identify the biochemical pathways that underlie neurodegenerative disease, such as AD; 2) to trace the effects of early-life toxin exposure on AD and neurodevelopmental disorders; 3) to study gene-environment interaction as conceptualized in the LEARn model; 4) to discover novel markers for diagnosis; and 5) to devise rational and molecular-based strategies for treatment. Our research leading to the discovery of novel biomarkers and drug targets for CNS disorders has high translational implications.
- Long JM, Ray B, Lahiri DK. (2014) MicroRNA-339-5p down-regulates protein expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer’s disease subjects. Journal of Biological Chemistry 289(8):5184-98.
- Lahiri DK, Maloney B, Long JM, Greig NH. (2014) Lessons from a BACE1 inhibitor trial: Off-site but not off base. Alzheimers Dementia S1552-5260(13)02917-8.
- Shah K, Lahiri DK (2014) Cdk5 activity in the brain: Multiple paths of regulation. Journal of Cell Science 127:2391-400.
- Lahiri DK, Sokol DK, Erickson CA, Ray B, Ho CY, Maloney, B (2013) Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway. Frontiers in Cellular Neuroscience 7:94 doi: 10.3389/fncel.2013.00094.
- Lahiri, D.K. (2012) Prions: A Piece of the Puzzle? Science 337(6099):1172.
- Long JM, Ray B, Lahiri DK (2012) MicroRNA-153 physiologically inhibits expression of amyloid-β precursor protein in cultured human fetal brain cells and is dysregulated in a subset of Alzheimer disease patients. Journal of Biological Chemistry 28(37),31298-310.
- Ray B, Long JM, Sokol DK, Lahiri DK (2011) Increased secreted amyloid precursor protein-α (sAPPα) in severe autism: Proposal of a specific, anabolic pathway and putative biomarker. PLoS One 6(6):e20405.