Srinivasa Subramaniam
Florida Atlantic University, FL·Neuroscience
Huntington disease (HD) is an inherited brain disorder that causes movement, thinking and psychiatric problems. It is caused by an expanded stretch of repeated CAG DNA letters in the huntingtin gene.
- Fields
Neuroscience
Biochemistry
Pharmacology
- Topics
Huntington disease
huntingtin
mHTT
- Grants
- 2 known grants, through May 2029
What they work on
- Identify the protein and RNA components on ribosomes that interact with mutant huntingtin (mHTT), the toxic protein that causes Huntington disease, using biochemical approaches.
- Determine how ribosomes stall on mHTT messenger RNA before the CAG repeat region, using ribosome profiling (Ribo-Seq) and biochemical reporter experiments.
- Define how Fmrp, a protein that restrains protein production at synapses, changes synaptic protein synthesis in Huntington disease, including in a humanized HD mouse model.
- Test whether Rhes, a striatum-enriched protein, spreads mHTT between brain regions through protein modifications and tunneling nanotube-like membrane bridges between neurons.
- Test whether SUMO1 tagging of mHTT blocks autophagy, the cell's waste-clearing system, allowing mHTT to build up and spread from striatum to cortex in Q175 HD knock-in mice.
More about the research
This expansion produces a mutant huntingtin protein, mHTT, which damages neurons. The striatum, a deep brain region involved in movement, is hit first. Many harmful effects of mHTT have been proposed, but how it actually kills neurons remains unclear. Both projects examine specific ways mHTT harms cells: one asks how it stalls the cell's protein-making machinery, and the other asks how it spreads between brain regions.
Why it matters
Huntington disease has no cure. By identifying how mutant huntingtin stalls ribosomes and how the Rhes and SUMO1 proteins help it spread through the brain, this work could reveal treatment targets that limit damage or slow its spread between brain regions. It could also inform diagnostics. The ribosome-stalling findings may also shed light on why neurons are vulnerable in related disorders such as Parkinson disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Hiroko Yano
Washington University in St Louis, MO·Neuroscience
Determine how a DNA methyltransferase inhibitor alters gene expression in individual brain cell types, including striatal neurons and glia, in Huntington's disease model mice, using single-nucleus RNA sequencing.
Alexander S Mankin
University of Illinois Chicago, IL·Microbiology & Immunology
Optimize small-molecule inhibitors of peptidyl-tRNA hydrolase, the bacterial enzyme that recycles unfinished protein chains, by synthesizing derivatives of sub-micromolar hits for stronger activity against the Klebsiella pneumoniae enzyme and better uptake into cells.
Henk L. Granzier
University of Arizona, AZ·Physiology
Determine whether the dominant nebulin deletion NEBΔ14–89 accumulates because of more transcript or more efficient translation, quantifying RNA and protein in patient biopsies and using ribosome profiling (Ribo-seq) to measure translational output, with STORM super-resolution imaging and contractile assays for structural and functional effects.
The school
Florida Atlantic University: 7 labs on PI Pages, $88M a year on research, 124 research doctorates a year.
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