Training Technologies Used:
Single-cell RNA sequencing, spatial transcriptomics, CRISPR-based gene perturbation, mouse behavioral cognitive assessments, and computational analysis of omics datasets.
- M.S., Cell Biology, University of Bern, Switzerland-2007
- Ph.D., Biochemistry, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland-2012
- Postdoc, Massachusetts Institute of Technology (MIT), Cambridge, MA, 2014-2020
Mathys H*, Boix CA*, Akay LA*, Xia Z, Davila-Velderrain J, Ng AP, Jiang X, Abdelhady G, Galani K, Mantero J, Band N, James BT, Babu S, Galiana-Melendez F, Louderback K, Prokopenko D, Tanzi RE, Bennett DA, Tsai LH, Kellis M. Single-cell multiregion dissection of Alzheimer's disease. Nature. 2024 Aug;632(8026):858-868. doi: 10.1038/s41586-024-07606-7. Epub 2024 Jul 24. PMID: 39048816. * these authors contributed equally.
Mathys H #*, Peng Z *, Boix CA *, Victor MB, Leary N, Babu S, Abdelhady G, Jiang X, Ng AP, Ghafari K, Kunisky AK, Mantero J, Galani K, Lohia VN, Fortier GE, Lotfi Y, Ivey J, Brown HP, Patel PR, Chakraborty N, Beaudway JI, Imhoff EJ, Keeler CF, McChesney MM, Patel HH, Patel SP, Thai MT, Bennett DA, Kellis M #, Tsai LH #. Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology. Cell. 2023 Sep 28;186(20):4365-4385.e27. doi: 10.1016/j.cell.2023.08.039. PMID: 37774677. # Corresponding author. * these authors contributed equally.
Sun N, Victor MB, Park YP, Xiong X, Scannail AN, Leary N, Prosper S, Viswanathan S, Luna X, Boix CA, James BT, Tanigawa Y, Galani K, Mathys H, Jiang X, Ng AP, Bennett DA, Tsai LH, Kellis M. Human microglial state dynamics in Alzheimer's disease progression. Cell. 2023 Sep 28;186(20):4386-4403.e29. doi: 10.1016/j.cell.2023.08.037. PMID: 37774678
Xiong X, James BT, Boix CA, Park YP, Galani K, Victor MB, Sun N, Hou L, Ho LL, Mantero J, Scannail AN, Dileep V, Dong W, Mathys H, Bennett DA, Tsai LH, Kellis M. Epigenomic dissection of Alzheimer's disease pinpoints causal variants and reveals epigenome erosion. Cell. 2023 Sep 28;186(20):4422-4437.e21. doi: 10.1016/j.cell.2023.08.040. PMID: 37774680
Dileep V, Boix CA, Mathys H, Marco A, Welch GM, Meharena HS, Loon A, Jeloka R, Peng Z, Bennett DA, Kellis M, Tsai LH. Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration. Cell. 2023 Sep 28;186(20):4404-4421.e20. doi: 10.1016/j.cell.2023.08.038. PMID: 37774679
Garcia FJ, Sun N, Lee H, Godlewski B, Mathys H, Galani K, Zhou B, Jiang X, Ng AP, Mantero J, Tsai LH, Bennett DA, Sahin M, Kellis M, Heiman M. Single-cell dissection of the human brain vasculature. Nature. 2022 Mar;603(7903):893-899. PMID: 35158371
Blanchard JW, Akay LA, Davila-Velderrain J, von Maydell D, Mathys H, Davidson SM, Effenberger A, Chen CY, Maner-Smith K, Hajjar I, Ortlund EA, Bula M, Agbas E, Ng A, Jiang X, Kahn M, Blanco-Duque C, Lavoie N, Liu L, Reyes R, Lin YT, Ko T, R'Bibo L, Ralvenius WT, Bennett DA, Cam HP, Kellis M, Tsai LH. APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature. 2022 Nov;611(7937):769-779. doi: 10.1038/s41586-022-05439-w. Epub 2022 Nov 16. PMID: 36385529
Mathys H *, Davila-Velderrain J *, Peng Z, Gao F, Mohammadi S, Young JZ, Menon M, He L, Abdurrob F, Jiang X, Martorell AJ, Ransohoff RM, Hafler BP, Bennett DA, Kellis M, Tsai LH. Single-cell transcriptomic analysis of Alzheimer's disease. Nature. 2019 Jun;570(7761):332-337. PMID: 31042697 *These authors contributed equally to this work.
Mathys H, Adaikkan C, Gao F, Young JZ, Manet E, Hemberg M, De Jager PL, Ransohoff RM, Regev A, Tsai LH. Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution. Cell Rep. 2017 Oct 10;21(2):366-380. PMCID: PMC5642107
Mathys H. *, Basquin J. *, Ozgur S., Czarnocki-Cieciura M., Bonneau F., Aartse A., Dziembowski A., Nowotny M., Conti E., Filipowicz W. (2014) Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression. Mol Cell. 54(5):751-65. PMID: 24768538 *These authors contributed equally to this work.
The Mathys Group develops and applies new functional genomics tools and methodologies to systematically decipher the molecular regulatory circuitry that controls the biology of brain cells in health and disease. With nearly one hundred billion neurons, which are connected by trillions of synapses, the human brain is arguably the most complicated biological structure in the known universe. How the brain is built and functions remains one of the greatest mysteries in science and understanding what causes dysfunction of the brain in the case of disease poses one of the greatest challenges in medicine. The research in our laboratory aims towards contributing to a better understanding of this enigmatic organ in health and disease focusing on the molecular mechanisms underlying Alzheimer’s disease. We use a multi-disciplinary approach, combining single-cell genomics, genome engineering, pooled genetic screens, and computational analysis, to dissect the inner workings of brain cells and their dysfunction in Alzheimer’s disease.
A major focus of our research are the cellular and molecular mechanisms underlying Alzheimer’s disease. The goal is to understand why some people age in a healthy way without cognitive impairment and why others do not and develop dementia? We hope that understanding the underlying cellular and molecular root causes of Alzheimer’s disease will facilitate the development of protective or preventive therapeutic strategies that promote healthy aging.
