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Mazahir T. Hasan

Principal Investigator

Ikerbasque Research Professor

Mazahir T. Hasan

Contact

Correo electrónico:Mazahir.Hasan@achucarro.org

Tel.:(+34) 94 601 8285

Science Park of the UPV/EHU
Sede Building, 3rd floor, Barrio Sarriena, s/n
E-48940 Leioa Spain

About me

I completed my undergraduate degrees in Chemistry and Biology at Boston University in the United States. I then earned a PhD in Biochemistry from Dartmouth College, solidifying my expertise in the field. Following my doctoral studies, I conducted postdoctoral research in synthetic biology, working directly with Nobel Laureate Professor Susumu Tonegawa at the Massachusetts Institute of Technology (MIT). I subsequently took on the role of group leader at the Max Planck Institute for Medical Research in Heidelberg, Germany, and at CharitƩ Medical University in Berlin, Germany, where I led significant research initiatives.

In my laboratory, we assertively leverage the power of synthetic biology to investigate cognitive processes, motor behavior, and the mechanisms of disease. We are at the forefront of research with an integrated systems approach that thoroughly examines the pivotal roles of essential components within brain circuits. These components—including various types of neurons (both pre-synaptic and post-synaptic), microglia, astrocytic processes, the extracellular matrix (ECM) including the perineuronal net, and the brain’s vascular system—constitute the crucial Ā«multipartiteĀ» synapse. These elements are non-negotiable for effective communication between and within cells, forming a robust network that connects the entire brain and ensures seamless, coordinated function. Our ongoing studies indisputably reveal that disruption of any one of these components dramatically impacts the others, impairing critical brain functions. This disruption is fundamental to understanding the onset and progression of diseases. Our research is essential for demystifying these dynamics and tackling the challenges they pose with determination.

Our lab has achieved groundbreaking technological advancements in the functional mapping of microcircuits and the manipulation of brain-wide circuits. Notably, my team and our collaborators were the first to showcase optical bioluminescence imaging in the living brains of mammals (Genesis. 2001;29(3):116-122). We have also led the way in applying genetically encoded calcium indicators (GECIs) in the mammalian brain to effectively map brain activity tied to sensory experiences (PLoS Biol. 2004;2(6):e163), achieving unparalleled single-cell and single action potential resolution (Nat Methods. 2008;5(9):797-804). Our innovation in utilizing optical fibers in freely moving mammals (Front Neural Circuits. 2010;4:9) set new standards in the field. These pioneering studies not only established the first applications of GECIs in the mammalian brain but also catalyzed further development and utilization of GECIs in systems neuroscience, decisively linking the functional roles of circuits to neurobiological processes, behavior, and disease mechanisms. Moreover, we have revolutionized the field with our development of tetracycline-controlled virus-delivered inducible gene deletion technology (Front Cell Neurosci. 2015;9:142, Mol Ther Nucleic Acids. 2016;5(4):e309). We provided the first direct evidence that the N-methyl-D-aspartate (NMDA) receptor in the primary motor cortex is critical for trace eyeblink conditioning, a classic model of declarative memory (Nat Commun. 2013;4:2258). To pinpoint cell assemblies activated during learning and memory retrieval, we introduced a transformative technology known as virus-delivered Genetic Activity-induced Tagging of cell Ensembles (vGATE). This pivotal work demonstrated for the first time that context-specific memory engrams reside in evolutionarily older brain structures, such as the hypothalamus, fundamentally expanding our understanding that memory representations (or engrams) are distributed across various brain regions, from older to newer structures (Neuron. 2019;103(1):133-146.e8).Ā  Using vGATE technology, we successfully identified circuits in the thalamus that correspond to a ā€œsocial engramā€ (Curr Biol. 2022 S0960-9822(22)01384-7). To establish the causal role of selectively targeted circuits in specific neurobiological processes, we developed the innovative virus-delivered Inducible Silencing of Synaptic Transmission (vINSIST) technology (Cereb Cortex. 2020;bhaa225). These advanced technologies empower us to manipulate specific brain circuits involved in learning, memory processes, and behavior. By integrating our cutting-edge genetic technologies, we have established for the first time that memory engrams are formed sequentially from one brain region to the next along a distinct neuroanatomical pathway (iScience. 2023 Sep 25;26(11):108050). Significantly, our breakthroughs have clarified that the dentate gyrus is essential for memory retrieval rather than memory storage, effectively resolving a long-standing controversy in the field (Mol Psychiatry. 2024 Apr 12).

We are pioneering groundbreaking technologies for comprehensive brain-scale Ā«integratedĀ» activity mapping using magnetic resonance imaging (MRI), backed by the prestigious BRAIN Initiative grant (NIH, USA) and the IKUR Neuroscience Program of the Basque Country. Moreover, we are developing cutting-edge genetic technologies that empower ā€œreal-timeā€, complete brain-scale activity mapping via MRI. These innovations will enable us to image the entire brain, effectively overcoming depth penetration limitations, and will deliver detailed functional connectomes. This opens unparalleled opportunities to link brain-wide circuits across diverse neurobiological processes, disease conditions, and post-therapeutic interventions in the same animals.

Our objective is to decisively identify and target pathological circuits at the Ā«multipartiteĀ» synapse throughout the entire brain to effectively combat brain pathologies (Mol Ther. 2013;21(8):1497-1506, Front Neurosci. 2023 17:1140679). We are rigorously developing and implementing cutting-edge genetic technologies that leverage adeno-associated viruses (AAVs), along with protein-based, lipid-based, and programmed cellular strategies. These innovative approaches will effectively protect against and treat neurological and psychiatric disorders in animal models, including Parkinson’s disease, Alzheimer’s disease, and epilepsy, while reversing the effects of aging. We are fully committed to translating these groundbreaking treatments into real solutions that will enhance human health.

We firmly believe in the critical importance of diversity and international collaboration in science across all cultures and nations. This conviction led us to establish “The Science Bridge“ initiative, a non-profit organization backed by scientists from around the globe. Our organization is dedicated to a science-driven mission that actively promotes world peace and prosperity (Neuron. 2017;96(4):730-735).

Publications

  1. Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation

    MuƱoz-Oreja, Mikel; Sandoval, Abigail; [...] Yoon, Wan Hee; Holt, Ian J
    Brain (May, 2024) DOI: 10.1093/brain/awae018
  2. Dentate gyrus is needed for memory retrieval

    Carretero-Guillén, Alejandro; Treviño, Mario; Gómez-Climent, María Ángeles; Dogbevia, Godwin K.; Bertocchi, Ilaria; Sprengel, Rolf; Larkum, Matthew E.; Vlachos, Andreas; Gruart, Agnès; Delgado-García, José M.; Hasan, Mazahir T.
    Molecular Psychiatry (Apr, 2024) DOI: 10.1038/s41380-024-02546-0
  3. Pre- and postsynaptic NMDA receptors are required for sequential printing of fear memory engrams

    Bertocchi, Ilaria; Rocha-Almeida, Florbela; Romero-BarragƔn, Marƭa Teresa; Cambiaghi, Marco; Carretero-GuillƩn, Alejandro; Botta, Paolo; Dogbevia, Godwin K.; TreviƱo, Mario; Mele, Paolo; Oberto, Alessandra; Larkum, Matthew E.; Gruart, Agnes; Sprengel, Rolf; Delgado-Garcƭa, JosƩ Maria; Hasan, Mazahir T.
    iScience (Nov, 2023) DOI: 10.1016/j.isci.2023.108050
  4. The neurogenetics of functional connectivity alterations in Autism: Insights from subtyping in 657 patients

    Rasero, Javier; Jimenez-Marin, Antonio; Diez, Ibai; Toro, Roberto; Hasan, Mazahir T.; Cortes, Jesus M.
    Biological Psychiatry (Apr, 2023) DOI: 10.1016/j.biopsych.2023.04.014
  5. Advances toward precision therapeutics for developmental and epileptic encephalopathies

    Bertocchi, Ilaria; Cambiaghi, Marco; Hasan, Mazahir T.
    Frontiers in Neuroscience (Apr, 2023) DOI: 10.3389/fnins.2023.1140679
  6. A thalamo-preoptic pathway promotes social grooming in rodents

    Keller, DÔvid; LÔng, TamÔs; CservenÔk, Melinda; Puska, Gina; Barna, JÔnos; Csillag, Veronika; Farkas, Imre; Zelena, Dóra; Dóra, Fanni; Küppers, Stephanie; Barteczko, Lara; Usdin, Ted B.; Palkovits, Miklós; Hasan, Mazahir T.; Grinevich, Valery; Dobolyi, ArpÔd
    Current Biology (Nov, 2022) DOI: 10.1016/j.cub.2022.08.062
  7. The Claustrum is Involved in Cognitive Processes Related to the Classical Conditioning of Eyelid Responses in Behaving Rabbits

    Reus-García, M. Mar; SÔnchez-Campusano, Raudel; Ledderose, Julia; Dogbevia, Godwin K.; Treviño, Mario; Hasan, Mazahir T.; Gruart, Agnès; Delgado-García, José M.
    Cerebral Cortex (Jan, 2021) DOI: 10.1093/cercor/bhaa225
  8. Predicting susceptibility and resilience in an animal model of post-traumatic stress disorder (PTSD)

    Colucci, Paola; Marchetta, Enrico; Mancini, Giulia Federica; Alva, Phoebe; Chiarotti, Flavia; Hasan, Mazahir T.; Campolongo, Patrizia
    Translational Psychiatry (Jul, 2020) DOI: 10.1038/s41398-020-00929-9
  9. Astrocytic p38α MAPK drives NMDA receptor-dependent long-term depression and modulates long-term memory

    Navarrete, Marta; Cuartero, Marƭa I.; Palenzuela, Rocƭo; Draffin, Jonathan E.; Konomi, Ainoa; Serra, Irene; ColiƩ, Sandra; CastaƱo-CastaƱo, Sergio; Hasan, Mazahir T.; Nebreda, Ɓngel R.; Esteban, JosƩ A.
    Nature Communications (Jul, 2019) DOI: 10.1038/s41467-019-10830-9
  10. A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System

    Hasan, Mazahir T.; Althammer, Ferdinand; [...] Charlet, Alexandre; Grinevich, Valery
    Neuron (Jul, 2019) DOI: 10.1016/j.neuron.2019.04.029