Dr. Biesecker's research focuses on understanding the relationship of genomic variation to health and disease. Currently, his laboratory is engaged in studies in two main areas: rare disorders of development and growth, and new approaches to hypothesis-generating clinical genomics research. The goals of his research program are to improve the medical care of patients affected by these disorders, provide generalized knowledge about the broad field of genetic disease and better understand basic mechanisms of normal and abnormal human development and physiology.
Dr. Biesecker's group studies several multiple anomaly syndromes, including Proteus syndrome and related mosaic overgrowth disorders and syndromic and non-syndromic polydactyly. Patients with these disorders exhibit various combinations of malformations, overgrowth, and birthmarks. Some patients have functional complications, such as intellectual disability, cardiovascular compromise. The Human Development Section has been recognized as an international leader in finding novel diagnostic and management approaches to these disorders, many of which are extremely rare. To further elucidate the clinical manifestations of these multiple anomaly syndromes, Dr. Biesecker's group takes advantage of the clinical resources available through the Mark O. Hatfield Clinical Research Center on the main NIH campus.
In order to find the genes that are altered in these syndromes, Dr. Biesecker's group ámassively-parallel sequencing, determines genotype-phenotype correlations and uses animal models to investigate the pathogenetic mechanisms of these disorders. Protocols aimed at understanding the disorders listed above, as well as other disorders having manifestations that overlap with these disorders, are actively recruiting individuals for study. Many patients are invited for evaluation at the Clinical Research Center, where they undergo extensive and sophisticated phenotypic assessments to generate data essential for understanding the range and variability of these rare disorders.
The second area of research is a highly collaborative large-scale medical sequencing project aimed at developing and exploring novel methods for conducting hypothesis-generating clinical genomics research. This project, aptly named ClinSeq«, uses massively parallel sequencing and other genomic interrogation methods as a tool for clinical research. The ClinSeq« study enrolls patients with a range of phenotypes from healthy through diseased, and the study will initially focus on cardiovascular disease. Patients undergo an initial medical evaluation for cardiovascular phenotypic features. Using massively parallel sequencing, billions of base pairs of sequence are being generated. The study will contribute to our understanding of the relative contributions of rare versus common genetic variants to common disease. The clinical focus of the ClinSeq« initiative has been expanded to include other genes that cause cancer susceptibility, malignant hyperthermia, cardiac muscle and rhythm disorders, and pharmacogenetics. This project is one of the leading international efforts in this exciting new area of research and is establishing new approaches to study design, informed consent, and subject participation for clinical genomics research.
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Last Updated: August 23, 2013