Researcher | Research Overview
A major focus over the years has been on gene discovery and improving methods for identification of pathogenic mutations, with return of these research results to patients in a clinical setting. Current research in the Beggs laboratory utilizes genomic approaches in human patients and animal models to understand the pathophysiology of rare genetic conditions, and to develop animal models for use in creating targeted therapies to treat these devastating childhood disorders.
- Gene discovery and disease mechanisms in neuromuscular disease:Much of our work has focused on understanding the genetics of congenital myopathies such as nemaline myopathy (NM), centronuclear myopathy, and related conditions. We have one of the largest data and specimen banks for patients with congenital myopathy, and have used this in contributing to discoveries of over a dozen disease genes for myopathies and related neuromuscular diseases. We continue to enroll patients, find new disease genes, and study the mechanisms leading to weakness in these children.
- Development of therapies for congenital myopathies:Availability of faithful animal models and our knowledge of the genetic basis for rare diseases has led to development and testing of new therapies for some of these conditions. We have tested and/or developed myostatin inhibition as well as both protein and gene replacement therapies for myotubular myopathy, resulting in the awarding of a patent for gene therapy of MTM and the creation of a biotechnology company that is now planning clinical trials of gene therapy. Collaborations with colleagues expert in muscle mechanics, have led to tests of drugs (troponin activators) to increase strength. Ongoing work is focusing on small molecule drug screens in zebrafish models and has already resulted in identification of several promising candidates for several neuromuscular mutants.
- Discovery of rare Mendelian disease genes: Recent technological advances have revolutionized our ability to sequence entire genomes. With the Manton Center for Orphan Disease Research, we have built an institutional infrastructure to ascertain, consent, and enroll patients with rare genetic diseases into a research program that allows us to study patients with unknown diagnoses who otherwise would be discharged and potentially lost to follow up without the benefit of any research investigation. The Center provides expertise in genomics to junior clinical and research staff and collaborative support in new gene discovery, which has led to numerous genetic discoveries as well as spawning new research projects throughout the hospital.
Researcher | Research Background
Alan H. Beggs PhD. is the Director of the Manton Center for Orphan Disease Research at Boston Children's Hospital and Sir Edwin & Lady Manton Professor of Pediatrics at Harvard Medical School. Following undergraduate studies at Cornell University, Dr. Beggs obtained his PhD in Human Genetics at Johns Hopkins University, with subsequent postdoctoral fellowship training in medical and molecular genetics at Johns Hopkins and Boston Children’s hospitals. He has general expertise in laboratory and clinical applications of genetics to human disease, and since 1992 has directed an independent research program in the Division of Genetics and Genomics.
Over the years, he has used the toolset of human molecular genetics to study normal biology and pathophysiology of a variety of disorders including muscular dystrophies, cardiac arrhythmias, developmental brainstem defects, hereditary anemias, sudden infant death syndrome, and congenital myopathies. Dr. Beggs has been a standing and ad hoc member of numerous NIH study sections and grant reviewer for the Muscular Dystrophy Association and March of Dimes. He is a member of several scientific advisory boards and boards of directors for nonprofit and commercial entities.