Boston Children’s Hospital, Division of Genetics and Genomics: Director, The Manton Center for Orphan Disease Research and Neuromuscular Disease Research Laboratory PI.
Harvard Medical School: Sir Edwin and Lady Manton Professor of Pediatrics in the Field of Genetics.
Broad Institute of MIT and Harvard: Associate Member, Program in Medical and Population Genetics.
Education summary
1978-1982: Cornell University School of Arts and Sciences, A.B. in Biology (Genetics). Ithaca, NY, USA.
1982-1987: Johns Hopkins University, PhD in Human Genetics. Baltimore MD, USA.
1987-1988: Johns Hopkins University School of Medicine, Department of Pediatrics. Fellowship in Medical Genetics with Prof. Barbara Migeon. Baltimore MD, USA.
1988-1991: Boston Children’s Hospital & Harvard Medical School, Division of Genetics. Fellowship in Molecular Genetics of Neuromuscular Disease with Prof. Louis Kunkel.
Career summary
My training is in human genetics, which I use to understand the genetic and cell biological basis for inherited human neuromuscular diseases. Throughout my career, I have used the toolset of human molecular genetics to study normal muscle biology and the pathophysiology of neuromuscular diseases. My primary research focus has been skeletal muscle-specific genes and their roles in muscular dystrophies and congenital myopathies. Significant accomplishments include early characterisation of mutations causing Duchenne/Becker and congenital muscular dystrophies, development of rapid and sensitive multiplexed PCR tests for muscular dystrophy, and gene discovery in many rare diseases, including nemaline, centronuclear, minicore and related congenital myopathies.
My laboratory has one of the largest well-characterised registries and DNA/tissue banks of patients representing the full spectrum of congenital myopathies, which we have used to facilitate many new disease gene discoveries leading to clinical confirmation and return of these results in a clinical setting. We have developed and used zebrafish, mouse and canine models of these conditions to study the pathophysiology and develop therapies. I am most proud of having helped lead the development of AAV-based gene therapy for XLMTM and assisting in the creation of a company that initiated the first-in-human trial for this. Despite significant toxicity and several deaths, the trial demonstrated remarkable efficacy before being stopped. I was the scientific founder of Kate Therapeutics (recently acquired by Novartis), a biotechnology startup developing a new class of highly potent myotropic MyoAAV vectors. The MTM1 vector we developed is just entering a new round of clinical trials.
What is the personal or professional achievement you’re most proud of?
Without a doubt, the personal achievement I am most proud of is my family – my wonderful partner and wife (also in medicine), and my two children (neither one interested in medicine!) who this year are both getting married and starting their own families.
Professionally, I am most proud of the positive impact I’ve been able to make for the several dozen students, technicians, postdocs and other trainees whose life paths (both within medicine and without) I’ve had the privilege to help mentor and guide. I’m proud of the collaborative approach to science that Lou Kunkel instilled in me, and that I’ve tried to model in my own career, and I’m proud of having had close friendships and working relationships with patients and patient advocacy organisations, and with public policy and advocacy groups such as the WMS, the ENMC, and MDA USA.
Professionally, my research output is reflected in more than 300 peer-reviewed articles (h-index 103, i10-index 313, 41,920 citations on Google Scholar).
Why did you first join the WMS?
In the 1990’s, during the early stages of my career, there was a lot of parochialism in our field. The United States had the Muscular Dystrophy Association, with many resources, but little interest in coordinating with other organisations. The ENMC was funded by the EU but put strict limits on participation by North American scientists because the MDA and other North American organisations declined to join and share funding. Conferences in the US were largely attended by people from North America and conferences in Europe and Asia were similar. When our founding Peripatetic Paediatrician, Victor Dubozitz, first conceived of the WMS he took a refreshing globalist view emphasising inclusiveness for members across the planet. WMS gives equal voice to members and constituents of every culture, and (almost) every continent (although I’m still waiting for our first Congress in Antarctica). Since becoming a member in 1999, the many congresses I have attended and activities I have been part of have led to numerous friendships, collaborations, and positive interactions with colleagues around the world. Our WMS Mission, to advance the science of neuromuscular disorders and care for people living with them, epitomises the goals of my career and provides me with important opportunities to have an impact beyond my hospital, university, and the patients and collaborators I work directly with.
What is your goal in joining the Executive Board?
As an Executive Board member for the past three years, I have had the privilege to help fashion and guide the policies of the WMS and be a part of evolving our organisation for the present and future challenges. As the Executive Board representative to the Sustainability Committee, I have become committed to empowering our Society and its members to be a force for good, not only on a scientific and medical level but also on a broader societal scale. My personal experiences developing and translating gene therapy from mice and dogs to first-in-human clinical trials have demonstrated the necessity and power of collaboration between academic scientists like myself, industry with greater resources and expertise, and patients and the patient advocacy community. I have advocated for closer ties between the WMS and both industry and patient organisations and will continue to do so as I feel that open sharing and collaboration across disciplines, cultures, and countries is critical in pursuing our Mission, especially in today’s fraught political climate. I look forward to serving you, my colleagues, for another three years.
