Faculty and Research

Biography

Our laboratory investigates the cellular, molecular, and network mechanisms that contribute to the pathogenesis of Alzheimer’s disease (AD), with particular focus on neuroimmune interactions and glial biology. We aim to better understand how immune responses in the brain are regulated and how they contribute to synaptic integrity, neuronal function, and cognitive decline during aging and disease.

Our work has contributed to identifying gene networks disrupted in aging and AD, highlighted the importance of glial regulatory pathways in disease progression, and explored how viral infections may influence neuroinflammation and neurodegeneration.

Our current research is centered on two major objectives: (1) investigating how glial cells, including microglia and astrocytes, are activated and regulated in aging and neurodegeneration, and how these immune responses impact disease progression, and (2) determining how the gut microbiome modulates brain physiology and immune signaling through the gut-brain-immune axis.

To address these questions, we use a multidisciplinary approach that integrates models of neurodegeneration with behavioral assays, transcriptomic and proteomic profiling, high-resolution imaging, and molecular analyses. Our long-term goal is to identify disease-modifying targets and develop novel therapeutic strategies to slow or halt the progression of Alzheimer’s disease.

Selected Publications:

  1. Readhead BP, Mastroeni DF, Wang Q, Sierra MA, de Avila C, Jimoh TO, Haure-Mirande JV, Atanasoff KE, Nolz J, Suazo C, Barton NJ, Orszulak AR, Chigas SM, Tran K, Mirza A, Ryon K, Proszynski J, Najjar D, Dudley JT, Liu STH, Gandy S, Ehrlich ME, Alsop E, Antone J, Reiman R, Funk C, Best RL, Jhatro M, Kamath K, Shon J, Kowalik TF, Bennett DA, Liang WS, Serrano GE, Beach TG, Van Keuren-Jensen K, Mason CE, Chan Y, Lim ET, Tortorella D, Reiman EM. Alzheimer’s disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain. Alzheimers Dement. 2024. Epub 20241219. doi: 10.1002/alz.14401. PubMed PMID: 39698934.
  2. Creus-Muncunill J, Haure-Mirande J-V, Mattei D, Bons J, Ramirez AV, Hamilton BW, Corwin C, Chowdhury S, Schilling B, Ellerby LM, Ehrlich ME. TYROBP/DAP12 knockout in Huntington’s disease Q175 mice cell-autonomously decreases microglial expression of disease-associated genes and non-cell-autonomously mitigates astrogliosis and motor deterioration. J Neuroinflammation. 2024;21(1):66. doi: 10.1186/s12974-024-03052-4.
  3. Perez Garcia G, Bicak M, Buros J, Haure-Mirande J-V, Perez GM, Otero-Pagan A, Gama Sosa MA, De Gasperi R, Sano M, Gage FH, Barlow C, Dudley JT, Glicksberg BS, Wang Y, Readhead B, Ehrlich ME, Elder GA, Gandy S. Beneficial effects of physical exercise and an orally active mGluR2/3 antagonist pro-drug on neurogenesis and behavior in an Alzheimer’s amyloidosis model. Frontiers in Dementia. 2023;2. doi: 10.3389/frdem.2023.1198006.
  4. Perez-Garcia G, Bicak M, Haure-Mirande JV, Perez GM, Otero-Pagan A, Gama Sosa MA, et al. BCI-838, an orally active mGluR2/3 receptor antagonist pro-drug, rescues learning behavior deficits in the PS19 MAPT(P301S) mouse model of tauopathy. Neurosci Lett. 2023:137080. Epub 20230116. doi: 10.1016/j.neulet.2023.137080. PubMed PMID: 36657633.
  5. Castranio E*, Hasel P*, Haure-Mirande J-V, Ramirez Jimenez A, Hamilton W, Kim R, et al. INPP5D limits plaque formation and glial reactivity in the APP/PS1 mouse model of Alzheimer’s disease. Alzheimers Dement. 2022; 1- 14. doi: 10.1002/alz.12821
  6. Haure-Mirande J-V, Audrain M, Ehrlich ME, Gandy S. Microglial TYROBP/DAP12 in Alzheimer’s disease: Transduction of physiological and pathological signals across TREM2. Mol Neurodegener. 2022;17(1):55. Epub 20220824. doi: 10.1186/s13024-022-00552-w. PubMed PMID: 36002854; PubMed Central PMCID: PMC9404585.
  7. Audrain M, Haure-Mirande JV, Mleczko J, Wang M, Griffin JK, St George-Hyslop PH, Fraser P, Zhang B, Gandy S, Ehrlich ME. Reactive or transgenic increase in microglial TYROBP reveals a TREM2-independent TYROBP-APOE link in wild-type and Alzheimer’s-related mice. Alzheimers Dement. 2020. Epub 2020/12/15. doi: 10.1002/alz.12256. PubMed PMID: 33314529.
  8. Readhead B.*, Haure-Mirande J-V. *., Mastroeni D., Audrain M., Fanutza T., Kim S. H, Blitzer R. D., Gandy S., Dudley J. T., Ehrlich M. E.. miR155 modulates a multiplex of behavioral and molecular pathological phenotypes in the APP/PSEN1 mouse model of Alzheimer’s pathology. Acta Neuropathol. 2020. doi: 10.1007/s00401-020-02185-z. (* co-first author)
  9. Readhead B, Haure-Mirande J.-V., Ehrlich M.E., Gandy S., Dudley J.T.. Clarifying the Potential Role of Microbes in Alzheimer’s Disease. Neuron. 2019;104(6):1036-7. Epub 2019/12/20. doi: 10.1016/j.neuron.2019.11.008. PubMed PMID: 31855627.
  10. Haure-Mirande J.-V., Wang M., Audrain M., FanutzaT., KimS. H., Schadt E. E., Heja S., Readhead B., Dudley J. T., Blitzer R. D., Zhang B.*, Gandy S.*, Ehrlich M. E.*. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in cerebral Abeta amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing Abeta burden. Mol Psychiatry. 2018. Epub 2018/10/05. doi: 10.1038/s41380-018-0255-6. PubMed PMID: 30283032.
  11. Audrain M., Haure-Mirande J.-V., Wang M., KimS. H., Fanutza T., Chakrabarty P., Fraser P., St George-Hyslop P. H., Golde T. E., Blitzer R. D., Schadt E. E., Zhang B., Ehrlich M. E., Gandy S. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau. Mol Psychiatry. 2018. doi: 10.1038/s41380-018-0258-3.
  12. Readhead B.*, Haure-Mirande J.-V.*, Funk C.C., Richards M.A., Shannon P., Haroutunian V., Sano M., Liang W.S., Beckmann N.D., Price ND, Reiman E.M., Schadt E.E., Ehrlich M.E., Gandy S., Dudley J.T.. Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron. 2018;99(1):64-82 e7. Epub 2018/06/26. doi: 10.1016/j.neuron.2018.05.023. PubMed PMID: 29937276. (* co-first author)
  13. Haure-Mirande J.-V., Audrain M., Fanutza T., Kim S.H., Klein W.L., Glabe C., Readhead B., Dudley J.T., Blitzer R.D., Wang M., Zhang B., Schadt E.E., Gandy S., Ehrlich M.E.. Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer’s pathology. Acta Neuropathol. 2017 Nov;134(5):769–788. PMCID: PMC5645450
  14. Readhead B.*, Haure-Mirande J.-V.*, Zhang B., Haroutunian V., Gandy S., Schadt E.E., Dudley J.T., Ehrlich M.E.. Molecular systems evaluation of oligomerogenic APP(E693Q) and fibrillogenic APP(KM670/671NL)/PSEN1(Δexon9) mouse models identifies shared features with human Alzheimer’s brain molecular pathology. Mol Psychiatry. 2016;21(8):1099–1111. PMCID: PMC4862938 (* co-first author)

For more publication information, please visit Pubmed:  https://www.ncbi.nlm.nih.gov/myncbi/1F5tMSZLb9Vkl/bibliography/public/

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