Hansruedi Mathys, PhD

  • Assistant Professor, Neurobiology

E-mail

mathysh@pitt.edu

Personal Website

Website Link

Education & Training

PhD, Friedrich Miescher Institute of Biomedical Research (FMI), Basel, Switzerland
Postdoc, Massachusetts Institute of Technology (MIT), Cambridge, MA

Campus Address

Biomedical Science Tower 3, 3rd Floor

One-Line Research Description

The cellular and molecular mechanisms underlying Alzheimer’s disease

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.

Representative Publications

Eberle AB, Stalder L, Mathys H, Orozco RZ, Mühlemann O. Posttranscriptional gene regulation by spatial rearrangement of the 3' untranslated region. PLoS Biol. 2008 Apr 29;6(4):e92. PMCID: PMC2689704

 

Zipprich JT, Bhattacharyya S, Mathys H, Filipowicz W. Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repression. RNA. 2009 May;15(5):781-93. PMCID: PMC2673060

 

Fabian MR, Mathonnet G, Sundermeier T, Mathys H, Zipprich JT, Svitkin YV, Rivas F, Jinek M, Wohlschlegel J, Doudna JA, Chen CY, Shyu AB, Yates JR 3rd, Hannon GJ, Filipowicz W, Duchaine TF, Sonenberg N. Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Mol Cell. 2009 Sep 24;35(6):868-80. PMCID: PMC2803087

 

Chekulaeva M. *, Mathys H. *, Zipprich J.T., Attig J., Colic M., Parker R., Filipowicz W. (2011) miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs. Nat Struct Mol Biol. 18(11):1218-26. PMCID: PMC3885283

* these authors contributed equally to this work

 

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

 

Gjoneska E, Pfenning AR, Mathys H, Quon G, Kundaje A, Tsai LH, Kellis M. Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease. Nature. 2015 Feb 19;518(7539):365-9. PMCID: PMC4530583

 

Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. PMCID: PMC5656389

 

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

 

Singer AC, Martorell AJ, Douglas JM, Abdurrob F, Attokaren MK, Tipton J, Mathys H, Adaikkan C, Tsai LH. Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load. Nat Protoc. 2018 Aug;13(8):1850-1868. PMID: 30072722

 

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

 

Adaikkan C, Middleton SJ, Marco A, Pao PC, Mathys H, Kim DN, Gao F, Young JZ, Suk HJ, Boyden ES, McHugh TJ, Tsai LH. Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron. 2019 Jun 5;102(5):929-943.e8. PMID: 31076275

 

Blanchard JW, Bula M, Davila-Velderrain J, Akay LA, Zhu L, Frank A, Victor MB, Bonner JM, Mathys H, Lin YT, Ko T, Bennett DA, Cam HP, Kellis M, Tsai LH. Reconstruction of the human blood-brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes. Nat Med. 2020 Jun;26(6):952-963. PMID: 32514169