Full Scientific Report

Program Overview

The Kaczorowski laboratory continues to push boundaries and take novel approaches to investigate and define the genetic principles underlying human resilience to dementia. Our goal is to establish the first system to bridge the gap between organismal and cellular resilience to Alzheimer’s disease (AD) and other neurodegenerative dementias. Ongoing, complementary, research initiatives are using a systems genetics approach to ultimately define and establish a cycle from discovery to preclinical testing that will provide a roadmap for resilience-based precision medicine and gerontology.
The work in the laboratory, including participation in large collaborative efforts, is focused on three broad interrelated goals.

Quantitatively assess resilience.  

There are many gene mutations known to cause Alzheimer's disease (AD), but there are also people that carry these mutations, who are nonetheless resistant, or resilient, to the disease-related mental decline. Similarly, there is significant variability in “normal” age-related mental decline, with some individuals resisting significant cognitive decline well into their 80s, and 90s. Our work, and that of others, has confirmed the genetic basis of resilience, as well as the existence of a host of environmental factors that interact in a complex manner within each individual to establish a personal level of resilience to AD and age-related mental decline. In order unravel these complex genetic and environmental interactions and identify strategies that make individuals resilient to cognitive decline we are developing the first in vitro system to quantitatively assess resilience to aging, AD pathologies and environmental insults at the cellular level in mice. Data from our complex customized mouse models are then subjected to sophisticated computational and statistical methods to “merge” the mouse data with human data. 

Model the spectrum of human neurodegenerative diseases.

 Differences in age and genetic background significantly affect how and when age-related cognitive decline and brain diseases like AD manifest. Dissecting the complex underlying mechanisms that create this variation is exceedingly difficult, if not impossible, with the use of human studies alone. We are using a sophisticated mouse-to-human approach to identify genetic factors in mice and then validate their relevance to cognitive aging in humans. We expect that this effort will produce a growing spectrum of novel mouse models that will allow us to surmount current experimental limitations to identify the specific factors that drive age-related cognitive decline and AD.

Predict individual risk and personalize intervention

Our ultimate goal is to develop preventative treatments and cures for AD and age-related dementia. The identification of novel genetic factors and mechanisms of memory decline is just a first step toward the development of both mechanistic-based treatments and personalized gene therapies. As underlying factors and mechanisms are validated, we will confirm predictive genetic variants or neurophysiological biomarkers that would permit earlier detection and intervention. Together this information will be used to develop powerful computational models to predict individual risk. This will set the stage for the initiation of the preclinical experiments that are a necessary step toward translating our research into clinical applications for AD and age-related dementia patients.

Selected Awards and Accomplishments of Kaczorowski Laboratory Members

Current Lab Members

  • Niran Hadad, Postdoctoral Fellow, The Jackson Laboratory (JAX)
    • Pyewacket Fellowship 
    • BrightFocus Foundation Fellowship
  • Andrew Ouellette, Graduate Student, University of Maine, GSBSE program
    • T32 Training Program Fellowship
  • Miko Dai, Research Intern, The Jackson Laboratory (JAX)
    • Invited international talk, IBANGs Neurodegenerative and Neuropsychiatric disorders Symposium (05/13/2021)
    • Brianna Gurdon, Graduate Student, University of Maine, GSBSE program
    • Project Lead, BRAINSPACE Award, Human Brain Project
    • Tom Murdy, Research Intern, The Jackson Laboratory (JAX)
    • Surjeet Singh, Postdoctoral Fellow, The Jackson Laboratory (JAX)

Alumni

  • Amy Dunn, Postdoctoral Fellow (alum)
    • STAT 2019 Wunderkind Award
    • Alzheimer’s Disease Association Research Award
    • 2018 The Jackson Laboratory (JAX) Scholar Awardee
    • Alfond Leaders Award Recipient (2018)
    • Current position, Associate Research Scientist, The Jackson Laboratory (JAX)
  • Jill King, Postdoctoral Fellow, The Jackson Laboratory (JAX)
    • Alzheimer’s Association Research Award
  • Stanley Yang, Co-Mentor on Alzheimer’s Association Research Fellowship
    • Current position, Scientist, Abbvie
  • David Anderson, Research Intern, The Jackson Laboratory (JAX)
    • Current position, MS Computer Science at Roux Institute at Northeastern Univ.
  • Sarah Heuer, Graduate Student, Genetics Track, The Jackson Laboratory (JAX)
    • AAIC Award, Best Lightning talk Reserve, Resilience and Protective Factors PIA
    • Predoctoral Fellow, Precision Genetics of Aging, Alzheimer’s Disease and Related Dementias (PGAD) T32 Training Program
    • Burroughs Wellcome Training Fellow
  • Patricia Doyle, Research Intern, The Jackson Laboratory (JAX)
    • Current position, PhD student, University of Kentucky
  • Alex Bednarek, Research Intern, The Jackson Laboratory (JAX)
    • Software Engineer, Plutoshift, Palo Alto, CA
  • Erin Merchant, Summer Intern and Student Intern, The Jackson Laboratory (JAX)
    • Developed workflow for brain-wide quantification of amyloid
  • Andrea Mirow, Summer Student, Undergraduate at Amherst College, MA
    • Kauffman Fellow, Amherst College, MA
  • Sarah Neuner, Graduate Student, Neuroscience Track, UTHSC
    • F31 NIA NRSA grant award (2015-2019)
    • HHMI 2020 Hanna Gray Fellow, Semi-finalist 
    • Current position, F32 NRSA Postdoctoral Fellow in Alison Goate’s lab, Mt. Sinai, NY
  • Glen Acosta, postdoctoral fellow
    • Current position, Scientist at Dicerna Pharmaceuticals, Cambridge MA
  • Travis McMurphy, Postdoctoral Fellow
    • Current position, AstraZeneca, Gaithersburg, MD
  • John Buttross, Undergraduate Research Assistant: Systems genetics of AD
    • Best paper award at 2017 Tennessee Academy of Science's meeting (role: mentor)
  • Robert H. Buckman and Joyce Mollerup Scholarship for Lasallian Fellow
    • Current position, Medical Student, UTHSC (MD, graduate class of 2022)
  • Michelle Kung, Summer Student, Undergraduate at Villanova, PA
    • JAX Summer Student
    • Semifinalist for the Fulbright Scholarship (2018-2019)
    • Current position, medical student, Temple University (class of 2023)
  • Lynda Wilmott, Postdoctoral Fellow, Neuroscience Track, UTHSC
    • Awarded American Federation of Aging Research Grant Award, 2015-2016
    • Awarded Alzheimer’s Disease Drug Discovery Scholarship, 2015
    • Current position, Staff Scientist, Washington University 
  • Kevin Hope, Graduate Student (EPhys), Neuroscience Track, UTHSC
    • Current position, Postdoctoral Fellow in Clement Chow’s lab, University of Utah
  • Iman Abutineh, Undergraduate Research Assistant: Immunohistochemistry (CBU)
    • Current position, Resident Physician, UTHSC (MD, graduate class of 2019)
  • Anna Zhu, M1 Medical Student Summer Research Rotation, UTHSC (class of 2018)
    • Gold Humanism Honor Society
    • Current position, Psychiatry Resident, UCLA Semel Institute for Neuroscience and Human Behavior

Recent Relevant Publications

A complete publication list is available here: https://www.ncbi.nlm.nih.gov/myncbi/catherine.kaczorowski.1/bibliography/public/

Funding Support

Media Links

 Articles on JAX’s website:

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