Postdoctoral Research

Morton Laboratory

After collaborating with Dr. Cynthia Morton during my graduate studies, she invited me to join her genetics laboratory at Brigham and Women’s Hospital (BWH). She soon opened my eyes to the rapidly evolving world of genetics, which was redefining research with the concepts of high-throughput analysis and big data compilation. I obtained an early postdoctoral NIGMS T32 grant to help train me in the field of genetics. Through weekly meetings at the Broad Institute, training alongside clinical geneticists and immersion in the Harvard/MIT genetics community, I have now come to appreciate fully how genetics can help advance our understanding of hearing loss. This training was put into practice while I worked alongside internationally recognized geneticists as part of the Development Genome Anatomy Project (DGAP). During my early work in Dr. Morton’s laboratory, we identified a human subject, referred to as DGAP056, who has a constellation of phenotypes, including profound congenital neurosensory HL and early-onset prostate cancer (developed at age 38). We discovered that DGAP056 had a de novo chromosomal translocation that broke the poorly annotated gene C2orf43. My initial work demonstrated that C2orf43 is expressed in the inner ear of zebrafish and provided preliminary data for an NIDCD F32 obtained in July of 2013. Per the goals of this grant, I developed a C2orf43 knockout (KO) mouse model to determine if this novel gene is involved in HL. After extensive auditory exams, I am delighted to report that we have demonstrated that loss of C2orf43 is sufficient to cause HL in 1-year-old male mice as well as prostate cancer, recapitulating the findings in DGAP056, in addition to obesity in female KOs. Recent evidence suggests that C2orf43 is crucial for a lipid/cholesterol pathway, prompting my investigations into genetically induced metabolic disorders associated with HL.

In addition to my major work which focused on DGAP056, I have been luckily enough to participate in several other DGAP studies, many with a hearing loss phenotype. We are now creating a pipeline in which chromosomal translocations can be rapidly sequenced to nucleotide level resolution, identified with standard nomenclature and analyzed with convergent genomics to rapidly establish genetic diagnosis. This platform should accelerate the rate of research and hopefully establish a clinical platform so that we can help end the diagnostic quest for those with chromosomal translocations.