Brigham and Women's Hospital
Associate Professor of Neurology
Harvard Medical School
Brigham and Women's Hospital
Dr. De Jager’s research focuses on understanding the role of human genetic variation in neuroimmunologic function and neurologic disease, with a particular interest in the pathophysiology and treatment of an inflammatory disease of the central nervous system, multiple sclerosis (MS) as well as in the understanding of cognitive decline in healthy, aging individuals. Specifically, in MS, he is (1) using genome-wide association testing methods to find susceptibility loci and disease-modifying loci for MS, (2) pursuing the functional characterization of susceptibility alleles that we have recently discovered, (3) refining a gene expression signature for MS, and (4) using association mapping techniques to discover genetic determinants of MRI and neuropsychologic phenotypes in MS and healthy individuals. In relation to cognitive decline associated with aging, Dr. De Jager and his research team are using the same techniques to explore the human genome as well the aging brain's epigenome and transcriptome for determinants of (1) the rate at which individuals lose cognitive function with aging and (2) the extent Alzheimer’s disease-related neuropathology accumulated by aging individuals at the time of death.
In preparation for his MS studies, he has established a new DNA sample collection with the support of the MS Center; he and his research team have collected over 3000 subjects from the MS Center in the past three years. These individuals have rich clinical phenotypes of disease course, severity, and response to treatment documented in the MS Center clinical database as well as serial MRIs at BWH with volumetric measurements such as lesion load and brain parenchymal fraction. He and his research team have published both an initial genome-wide association scan for MS susceptibility (NEJM 2007) as well as a subsequent meta-analysis of MS genome scans (Nat Genet 2009) that report the discovery of multiple susceptibility loci. Dr. De Jager is now beginning to explore the relationship of clinical and radiographic phenotypes to genetic variation. Ultimately, he and his team hope to develop diagnostic and prognostic algorithms for use in the clinic.
To explore the function of genetic variation associated with human disease, Dr. De Jager created the PhenoGenetic Project, a resource that provides fresh blood samples from over 1600 individuals based on their genotype or other characteristics. His current work focuses on the effect of MS and AD related genetic variation in the function of the immune system. An important component of this effort is the generation of an atlas of gene expression related to genetic variation in 600 healthy subjects.
In the field of cognitive decline, Dr. De Jager and his team are currently analyzing genome-wide association data in relation to two phenotypes: (1) a measure of Alzheimer’s disease-related pathology gathered from over 700 autopsied subjects and (2) longitudinal neuropsychological data that documents each individual’s trajectory of cognitive decline in over 8000 subjects. In parallel, the DNA methylome and genome-wide H3K9Ac profile from 1000 subjects is being investigated to identify loci that influence our outcome measures. RNAseq data is now being generated on these subjects to better characterize the functional consequences of different loci.
Dr. De Jager’s research interest therefore lies in human genetics and neurology, with a particular interest in MS and neurodegeneration. Human genetics and epigenomics, computational methods and cellular immunology are some of the techniques that he and his team are using today. This selection of method will doubtlessly evolve as he and his research team continue to explore the function of the genetic variation that they identify.
This page was last modified on 9/18/2015