Yuhua Song
University of Alabama at Birmingham, AL·Biomedical Engineering
Some of the strongest genetic risk factors for late-onset Alzheimer's disease are single-letter changes in TREM2. TREM2 is a receptor on immune cells that senses molecules and switches on immune activity.
- Fields
Biomedical Engineering
Biophysics
Neuroscience
- Topics
Alzheimer's disease
triggering receptor expressed on myeloid cells 2
drug repositioning
- Grants
- 2 known grants, through Feb 2028
What they work on
- Identify endogenous ligands that bind the basic and/or hydrophobic sites of TREM2, an immune receptor linked to Alzheimer's risk, using virtual screening validated by biophysical and cell experiments.
- Determine the allosteric effects of ligand binding at one TREM2 site on the other, and how disease-linked TREM2 variants change endogenous ligand binding.
- Screen available drugs, including FDA-approved ones, for binding to TREM2's basic or hydrophobic site with unbiased virtual screening and biophysical and cellular validation.
- Test whether TREM2-binding drugs restore TREM2–ApoE binding and immune activation lost to Alzheimer's-associated TREM2 variants.
More about the research
Disease-linked TREM2 variants weaken its ability to bind these molecules and send signals. Both projects study how molecules attach to TREM2 at its two binding sites, a positively charged 'basic' site and an oily 'hydrophobic' site. A key idea is allosteric effects, where binding at one site changes binding at the other. Each project combines computer screening with laboratory binding and cell experiments. One project seeks the body's own TREM2 partners; the other seeks existing drugs that could act on TREM2.
Why it matters
People who carry TREM2 variants face higher Alzheimer's risk because the receptor's immune signaling is weakened. Identifying the molecules and existing drugs that bind TREM2 could give a molecular basis for repurposing approved medicines, alone or in combination, to restore TREM2 activity. The findings may also bear on other neurodegenerative and inflammatory diseases involving TREM2.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Tae-Wan Kim
Columbia University, NY·Neuroscience
Determine how the neuronal signal SEMA3A promotes β-amyloid uptake and a disease-associated microglia gene profile in human iPSC-derived microglia (iMGLs), independently of the TREM2 receptor.
Katrin I. Andreasson
Stanford University, CA·Neuroscience
Test whether reprogramming energy metabolism in aging microglia and blood macrophages, by blocking inflammatory PGE2 signaling, can prevent or reverse cognitive decline in aging and Alzheimer's model mice.
Marina Sirota
University of California-San Francisco, CA·Computer Science
Validate repurposed drugs predicted to reverse neuron and glia disease signatures, using iPSC-derived co-cultures and chronic dosing in 5xFAD and hTAU Alzheimer's mice, and measure amyloid, neuroinflammation and synapse loss.
The school
University of Alabama at Birmingham: 45 labs on PI Pages, $866M a year on research, 166 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.