Assistant Professor of Neurology
Department of Neurology
Bryan Alzheimer's Disease Research Center and
Duke Institute for Genome Sciences & Policy
Duke University Medical Center
Durham, NC 27710
905 S. LaSalle Street
GSRB I, Room 2005
Durham, NC 27710
Our research interests center around the genetics of complex neurological diseases. Specifically, we focus on two major areas:
1. The significance and functional consequences of genomic regions/genes associated with neurodegenerative-diseases
Our work capitalizes on the identification of genomic regions and/or genes as highly significant genetic risk factors through candidate-genes and genome-wide based association studies.
Our goal is to reveal the mechanism by which the associated regions contribute to disease susceptibility. Pinpointing the causal genetic variants within a genomic region that has been implicated in disease by association studies is a current, though a challenging need.
First, this is due to the fact that most genetic variants were implicated due to linkage disequilibrium with the causal variant, which only occasionally was directly called. Moreover, many identified associations map to non-coding regions. Thus for the majority of the complex disease associated genomic region the precise causal variant remains unknown. Primarily we test the hypothesis that changes in expression levels of normal protein can lead to neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases.
Using post-mortem human brain tissues, cell-based systems and humanized mouse model we have been studying the effect of genetic variations within a genomic region of interest on gene expression pattern.
In particular we investigate three model genes: SNCA, implicated in Parkinson’s disease; TOMM40 and SORL1 involved in Alzheimer’s disease. By determining the functional association of genetic variants with differential expression we advance the identification of novel causal variants and hence impact our understanding of the genetic factors and molecular mechanisms underlying common neurodegenerative disorders
The lab is also member of both the Bryan Alzheimer’s Disease Research Center (ADRC) and the Duke University’s Institute for Genome Sciences & Policy that provides the foundation for the establishment of this unique collaborative program between these two centers at Duke.
Using a comprehensive battery of the different neuropsychiatric tests we are currently developing endophenotypes to establish a thorough phenotypic characterization of mild cognitive impairment (MCI) vs. normal controls. In addition we have initiated fine phenotypic characterization to identify individuals over the age of 85 who we define as successful cognitive aging. These cognitive endophenotypes will be used in genetic tests by candidate genes and whole genome approaches to investigate the genetics basis of cognitive changes in elderly.
The Chiba-Falek lab is working very closely with the Deane Drug Discovery Laboratory headed by Dr. Allen Roses.