Personal profile
Research interests
The Brett lab is focussed on using the methods of structural biology, biophysics, biochemistry, and cellular biology to understand molecular mechanisms underlying disease pathologies. Our current focusses are on chronic inflammatory airway diseases and Alzheimer's disease.
Our research on chronic airway disease is focussed on cystic fibrosis. We have identified a unique family of regulator proteins, the CLCA family, that regulate the TMEM16 family of chloride channels. Our research investigates the structural and biophysical mechanisms of CLCA potentiation of TMEM16 channels, as well as their role in airway biology and mucosal immunology.
Our research on Alzheimer's disease focusses on microglial receptors and their role in AD pathogenesis. Current focus is on TREM2, a scavenger receptor expressed on microglia that signals for important microglial functions. We use structural, biophysical, and cellular methods to understand how various ligands engage and signal through TREM2.
Clinical interests
cystic fibrosis
Education activities and interests
I currently serve as Co-Director for the Biochemistry, Biophysics, and Structural Biology (BBSB) PhD program and serve on the steering committee. I am committed to maintaining and increasing the quality of the BBSB program and supporting its students, as well those of other DBBS programs.
I serve as a coursemaster for the Structural Biology Journal Club.
Mentoring
My mentoring approach involves working closely with trainees on all aspects of their project and career objectives. Past trainees have been very successful in obtaining competitive fellowships, and have progressed to prominent independent positions.
The Brett lab is committed to support, wellness, diversity, and inclusion.
Available to Mentor:
- PhD Students
- High School Students
- Undergraduate Students
- Post-Baccalaureate Students
- Health Professions (Medical, OT, PT, Dental, Audiology, etc.) Students
- Postdocs
- Residents and Fellows
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Collaborations and top research areas from the last five years
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Cholecalciferol (vitamin D3) is an agonist of the Alzheimer's disease–associated immune receptor TREM2
Dean, H. B., Tuckey, R. A., Greer, R. A., Greven, J. A., Yang, S. Z., Elston, D. S., Eastep, G. N., Song, Y., Brett, T. J., Song, Y. & Roberson, E. D., Mar 2026, In: Neurotherapeutics. 23, 2, e00867.Research output: Contribution to journal › Article › peer-review
Open Access -
Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer’s disease ligands
Greven, J. A., Wydra, J. R., Greer, R. A., Zhi, C., Price, D. A., Svoboda, J. D., Camitta, C. L. M., Washington, M., Leung, D. W., Song, Y., Alexander-Brett, J. & Brett, T. J., Dec 2025, In: Molecular neurodegeneration. 20, 1, 3.Research output: Contribution to journal › Article › peer-review
Open Access20 Link opens in a new tab Scopus citations -
TREM2-apoE3 interactions and Alzheimer's disease: Molecular and structural insights and effects of TREM2 R47H and apoE4 variants
Greer, R. A., Tuckey, R. A., Dean, H. B., Brett, T. J., Roberson, E. D. & Song, Y., Oct 2025, In: Alzheimer's and Dementia. 21, 10, e70729.Research output: Contribution to journal › Article › peer-review
Open Access2 Link opens in a new tab Scopus citations -
Modulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells
Sala-Rabanal, M., Yurtsever, Z., Berry, K. N., McClenaghan, C., Foy, A. J., Hanson, A., Steinberg, D. F., Greven, J. A., Kluender, C. E., Alexander-Brett, J. M., Nichols, C. G. & Brett, T. J., Jul 2024, In: Journal of Biological Chemistry. 300, 7, 107432.Research output: Contribution to journal › Article › peer-review
Open Access4 Link opens in a new tab Scopus citations -
Multimerization of TREM2 is impaired by Alzheimer's disease–associated variants
Dean, H. B., Greer, R. A., Yang, S. Z., Elston, D. S., Brett, T. J., Roberson, E. D. & Song, Y., Sep 2024, In: Alzheimer's and Dementia. 20, 9, p. 6332-6350 19 p.Research output: Contribution to journal › Article › peer-review
Open Access12 Link opens in a new tab Scopus citations