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Alex R. DeCasien , Ph.D., Principal Investigator
The Computational and Evolutionary Neurogenomics Unit studies how sex, aging, and evolutionary history shape molecular variation in the human brain and influence risk for neurodevelopmental and neurodegenerative disease. Our work integrates single-cell and population-scale genomics with comparative biology to identify mechanisms underlying sex-biased brain aging and disease vulnerability.
A central focus of the group is understanding how sex chromosomes and sex hormones interact with aging to shape cell-type-specific brain trajectories. Using large human single-nucleus RNA-sequencing datasets, we have shown that sex differences in the adult brain are highly structured across regions and cell types and overlap with genetic risk for brain disorders. We are extending this work by integrating endocrine measures to examine how menopause and hormonal aging influence brain gene expression.
In parallel, we investigate chromosome-level mechanisms of aging and disease, including the function of homologous X-Y genes, age-related erosion of X-chromosome inactivation, and sex chromosome loss. Our group also contributes computational and conceptual expertise to multidisciplinary studies within the Laboratory of Neurogenetics and across NIH.
Finally, we use comparative primate genomics to place human brain aging in an evolutionary context and to inform model selection for translational neuroscience.
Portfolio/Research Areas
- Sex differences in brain aging and neurodegeneration
- Variation in sex chromosomes and X-chromosome inactivation
- Single-cell and multi-omic analyses
- Population-scale risk architecture of neurodegenerative disease
- Comparative genomics and primate brain evolution
- Translational frameworks for aging and Alzheimer’s disease
Key Findings and Publications
DeCasien, A.R., Tsai, K., Liu, S., Thomas, A., Raznahan, A. Evolutionary divergence between homologous X-Y chromosome genes shapes sex-biased biology . (2025). Nature Ecology & Evolution, 9(3), 448-463.
DeCasien, A.R., Chiou, K.L., Testard, C., Mercer, A., Negrón-Del Valle, J.E., Bauman Surratt, S.E., González, O., Stock, M.K., Ruiz-Lambides, A.V., Martínez, M.I., Cayo Biobank Research Unit, Antón, S.C., Walker, C.S., Sallet, J., Wilson, M.A., Brent, L.J.N., Montague, M.J., Sherwood, C.C., Platt, M.L., Snyder-Mackler, N., Higham, J.P. Evolutionary and biomedical implications of sex differences in the primate brain transcriptome. (2024). Cell Genomics, 4(7), 100589.
Chiou, K.L., DeCasien, A.R., Testard, C., Spurrell, C.H., Gogate, A.A., Wilson, M., Pliner, H.A., Mercer, A., Negrón-Del Valle, J.E., Janiak, M.C., Bauman, S.E., González, O., Compo, N.R., Stock, M.K., Ruiz-Lambides, A.V., Martínez, M.I., Cayo Biobank Research Unit, Melin, A.D., Antón, S.C., Walker, C.S., Sallet, J., Starita, L.M., Shendure, J., Higham, J.P., Brent, L.J.N., Montague, M.J., Platt, M.L., Snyder-Mackler, N. Multiregion transcriptomic profiling of the primate brain reveals signatures of the aging social environment . (2022). Nature Neuroscience, 25(12), 1714-1723.
DeCasien, A.R., Guma, E., Liu, S., Raznahan, A. Sex differences in the human brain: a roadmap for more careful analysis and interpretation of a biological reality . (2022). Biology of Sex Differences, 13(1), 1-21.
DeCasien, A.R., Barton, R.A., Higham, J.P. Understanding the human brain: insights from comparative biology . (2022). Trends in Cognitive Sciences, 26(5), 432-445.
DeCasien, A.R., & Higham, J.P. Primate mosaic brain evolution reflects selection on sensory and cognitive specialization . (2019). Nature Ecology & Evolution, 3(10), 1483.
DeCasien, A.R., Williams, S.A., & Higham, J.P. Primate brain size is predicted by diet but not sociality . (2017). Nature Ecology & Evolution, 1(5), 0112.