William Hendriks, PhD

Instructor in Investigation
Neurology, Mass General Research Institute
Instructor in Neurology
Harvard Medical School
Research Staff
Neurology, Massachusetts General Hospital
Affiliate Faculty
Harvard Stem Cell Institute
PHD Vrije Universiteit 2008
genome engineering; mitochondrial genetics; parkinsons's disease; stem cell-based disease modeling; x-linked dystonia parkinsonism In 2014 I joined the MGH Collaborative Center for X-Linked Dystonia-Parkinsonism (CCXDP), an international consortium focused on a rare and fatal neurodegenerative disease affecting individuals with maternal ancestry to the Philippines. As an Instructor in Neurology at the center, I established an hiPSC-based cellular platform comprising XDP individuals and unaffected control relatives for interrogating candidate gene variants. This work enabled a major collaborative effort combining genomic and transcriptomic analyses of generated cell lines, which culminated in the discovery of a disease-specific retrotransposon insertion bearing a DNA repeat expansion, the length of which correlates with clinical disease severity. These results were published in two joint reports:  one in Cell and another in PNAS.  My current focus for CCXDP is to develop new CRISPR methods as (1) tools for studying the functional consequences of specific elements within the XDP-specific retrotransposon; and (2) a potential gene therapy approach to excise the pathogenic retroelement in human patient neurons.
Another line of research that I am developing is to study the contribution of somatic mitochondrial DNA variation in the brain to neurodegenerative disease, specifically Parkinson's disease (PD). Damage to the mitochondrial genome due to mitochondrial oxidative stress is associated with normal aging, but excess mitochondrial DNA damage has been associated with PD aetiology. I am developing in vitro, human induced pluripotent stem cell-based PD models to study mitochondrial DNA damage-induced neuronal degeneration with the aim to find if increased mitochondrial DNA damage is an early indicator of PD and whether mitochondrial DNA-containing extracellular vesicles (EVs) might be a potential early PD biomarker.

Dept. of Neurology: Bragg Lab Publications
CNY-Building #149
149 13th Street
Charlestown, MA 02129-2000