27419-Lasagna Reeves, Cristian
Faculty

Cristian A. Lasagna Reeves, PhD

Assistant Professor of Anatomy, Cell Biology & Physiology

Phone 317-274-7830
Address
Neurosciences Research Building
320 W. 15th Street, NB-214G

Indianapolis, IN 46202

Bio

My scientific career has revolved around the study of protein aggregation in neurodegenerative diseases with a special emphasis in the role of tau pathogenesis in Alzheimer’s disease and related dementias. For several years, my work has focused on the relevance of tau oligomers in the pathogenesis of AD. My studies yielded evidence that this pre-filamentous form of tau is a possible biomarker and target for the diagnosisand treatment of AD. My work in characterizing tau and tau oligomers not only challenged the traditional view of tau neurofibrillary tangles as responsible for neurodegeneration in AD, but also may lead to therapies that target tau oligomers to combat neurodegeneration.

 

Currently, my laboratory focuses in understanding the role of tau in AD/Alzheimer’s Disease and Related Dementias (ADRD), with special emphasis in the mechanism(s) involved in tau aggregation and propagation and the contribution of vascular damage and neuroinflammation to synaptoxicity associated to tau aggregation. A detail description of my lab research and publications can be found at www.lasagnareeveslab.com

Titles & Appointments

  • Assistant Professor of Anatomy, Cell Biology & Physiology
  • Investigator, Stark Neuroscience Research Institute.
  • Education
    2010 PhD University of Texas Medical Branch at Galveston
    2008 MS University of Chile
    2005 BS University of Chile
  • Research

    Tau Physiology and pathology in neurodegeneration.

     

    Pathological aggregation of the microtubule-associated protein tau and the preponderance of neurofibrillary tangles (NFT) or other inclusions containing tau are the defining histopathological features of Alzheimer disease (AD) and over 20 other neurodegenerative tauopathies. Therefore, the study of the physiological and pathological function of tau is key to understand and treat these neurodegenerative diseases. Hence, the main focus of my lab is to comprehensive elucidated the role that tau physiology plays in neurodegenerative tauopathies.

     

    Investigating the role of tau native interactors on tau amyloidogenic properties and disease pathogenesis.

     

    We study the role of different physiological partners of tau in its stabilization, accumulation, localization, folding, misfolding, and toxicity.  To pursue this, we combined in vitro structural and cellular techniques with mouse genetic and pharmacological manipulations to determine the effect of a specific interactor on tau toxicity in neurodegenerative tauopathies. This research strategy is suitable not only for tau, but is also applicable to the study of other neurodegenerative diseases characterized by toxic protein aggregation.

     

    Role of AMPK-related kinases in the pathogenesis of Alzheimer’s disease and how modulation of its levels affects tau-induced pathology.

     

    At the pathological level, the correlation between NFT and disease progression has been studied extensively with conflicting results; the mechanisms linking the pathological aggregation of tau with synaptic dysfunction and neurodegeneration are poorly understood. An emerging view is that NFT themselves are not the true toxic entity in tauopathies, but rather lowering tau levels is most critical. I previously demonstrated how reducing the levels of Nuak1, an AMPK-related kinase, decreases tau a reverses phenotypes in a tauopathy mouse model (C.A. Lasagna-Reeves, Neuron, 2016). Currently in my lab we are continuing dissecting the physiological and pathological relation between AMPK-related kinases and tau.

     

    Formation of tau pore-like structures in neurodegenerative tauopathies.

     

    Annular protofibrils (APFs) represent a new and distinct class of amyloid structures formed by disease- associated proteins. In vitro, these pore-like structures have been implicated in membrane permeabilization and ion homeostasis via pore formation. In previous studies I reported that tau and Aβ APFs are in a pathway distinct from fibril formation in vitro and in vivo. These findings establish the pathological significance of APFs in vivo and highlight their suitability as therapeutic targets for several neurodegenerative diseases. Currently in the lab we are studying the role of tau in the plasma membrane and dissecting the mechanism of APFs formation.

     

  • Awards
    Org: Keystone Symposia
    Desc: Underrepresented Trainee Scholarship to attend to Keystone Symposia “Alzheimer’s Disease – From Fundamental Insights to Light at the End of the Translational Tunnel"
    Scope: International
    Date: 2014-03-17
    Org: University of Texas Medical Branch
    Desc: Dr. and Mrs. Seymour Fisher Academic Excellence Award in Neuroscience
    Scope: University
    Date: 2010-08-20
    Org: University of Texas Medical Branch
    Desc: Jen Chieh and Katherinen Huang Scholarship Award for excellence in Neuroscience
    Scope: University
    Date: 2010-05-15
    Org: Baylor College of Medicine
    Desc: Postdoc Dean’s Award of Excellence
    Scope: University
    Date:

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