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Adjunct Professor of Genomics and Precision Medicine
Office Phone: 202-476-6029
Department: Genomics and Precision Medicine
- PhD, Johns Hopkins University, 1987
I earned my Ph.D. in Genetics at Johns Hopkins University and then pursued post-doctoral training with Louis Kunkel at Boston Children’s Hospital working on Duchenne muscular dystrophy gene and protein identification. My research has focused on molecular genetics, pathogenesis, and therapeutics of neuromuscular disease. The research group I directs at Children’s Hospital in DC hosts research laboratories of about research faculty, with a focus on ‘omics applications to pediatric health problems.
Recent areas of particularly interest to me and my own laboratory are development of therapeutics for Duchenne muscular dystrophy, and understanding the molecular genetics of muscle in health and disease. Relevant to drug development, I have co-founded ReveraGen Biopharma, where a lead dissociative steroid (VBP15) is being developed muscular dystrophy and other disorders. VBP15 development is funded by Foundation to Eradicate Duchenne (FED), the NIH TRND program, and Muscular Dystrophy Association Venture Philanthropy. I have been assisting in the development of systemic oligonucleotide therapeutics (exon skipping), in collaboration with AVI and other academic laboratories. I directs a Program Project on exon skipping from the Department of Defense, with research projects on small molecules to enhance potency of oligonucleotide drugs (Carrie Miceli, UCLA), oligo conjugates to increase cell delivery (Qi Lu, Carolinas Medical Center), and large animal studies of efficacy (Toshifumi Yokota and Shin’ichi Takeda, Tokyo), with a pre-clinical testing core (Kanneboyina Nagaraju, Children’s DC). I am Co-Director of a NIAMS Center of Research Translation (P50 CORT) together with Paula Clemens (Pittsburgh), with projects on studies of antisense ‘skipped’ dystrophin protein function, optimization of multiple morpholino drugs, and an international natural history study of Becker muscular dystrophy. I helps direct a U54 Center of Pediatric Pharmacology focused on studies of chronic kidney toxicity with long-term morpholino oligonucleotide treatment (with John Vandenanker, and Edward Connor). I served as PI on GLP toxicity studies of morpholinos, supported by the Department of Defense, that enabled US trials of high dose IV morpholino in Duchenne muscular dystrophy.
I serves a Scientific Director of the 24 site Cooperative International Neuromuscular Research Group (CINRG), and as PI of a NIH National Center for Medical Rehabilitation Research. I am board-certified by the American Board of Medical Genetics in Clinical Molecular Genetics.
Hoffman EP, Bronson A, Levin AA, Takeda S, Yokota T, Baudy AR, Connor EM. Restoring dystrophin expression in duchenne muscular dystrophy muscle progress in exon skipping and stop codon read through. Am J Pathol. 2011 Jul;179(1):12-22.
Yokota T, Hoffman E, Takeda S. Antisense oligo-mediated multiple exon skipping in a dog model of Duchenne muscular dystrophy. Methods Mol Biol. 2011;709:299-312.
Yokota T, Lu QL, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E. Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Ann Neurol. 2009 Jun;65(6):667-76.
Yokota T, Takeda S, Lu QL, Partridge TA, Nakamura A, Hoffman EP. A renaissance for antisense oligonucleotide drugs in neurology: exon skipping breaks new ground. Arch Neurol. 2009 Jan;66(1):32-8.
Hoffman EP. Skipping toward personalized molecular medicine. N Engl J Med. 2007 Dec 27;357(26):2719-22.
Selected From 409: Peer-reviewed (305); Solicited (106).
- Hoffman EP, Monaco AP, Feener CC, and Kunkel LM. Conservation of the Duchenne muscular dystrophy gene in mice and humans. Science 1987; 238: 347-350.
- Hoffman EP, Brown RH, and Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987; 51: 919-928.
- Rojas CV, Wang JZ, Schwartz LS, Hoffman EP, Powell BR, and Brown RH. A methionine to valine mutation in the skeletal muscle sodium channel alpha-subunit in human hyperkalemic periodic paralysis. Nature 1991; 354: 387-389.
- Rudolph JA, Spier SJ, Byrns G, Rojas CV, Bernoco D, and Hoffman EP. Periodic paralysis in Quarter Horses: a sodium channel mutation disseminated by selective breeding. Nature Genet 1992; 2: 144-147.
- Chen YW, Zhao P, Borup R, and Hoffman EP. Expression profiling in the muscular dystrophies: Identification of novel aspects of molecular pathophysiology. J Cell Biol 2000; 151: 1321-1336.
- Seo J, Bakay M, Chen YW, Hilmer S, Shneiderman B, Hoffman EP. Interactively optimizing signal-to-noise ratios in expression profiling: project-specific algorithm selection and detection p-value weighting in Affymetrix microarrays. Bioinformatics. 2004; 20: 2534-44.
- Zhao P, Hoffman EP. Embryonic myogenesis pathways in muscle regeneration. Dev Dyn. 2004 Feb;229(2):380-92.
- Tumor Analysis Best Practices Working Group. Expression profiling--best practices for data generation and interpretation in clinical trials. Nat Rev Genet. 2004; 5: 229-37.
- Gordon ES, Gordish-Dressman HA, Devaney J, Clarkson P, Thompson P, Gordon P, Pescatello LS, Hubal MJ, Pistilli EE, Gianetti G, Kelsey B, Hoffman EP. Nondisease genetic testing: reporting of muscle SNPs shows effects on self-concept and health orientation scales. Eur J Hum Genet. 2005; 13: 1047-54.
- Friedmann T, and Hoffman EP. Genetic doping in sport. In Performance-enhancing technologies in sports: Ethical, conceptual and scientific issues. Ed. Thomas H Murray et al. Johns Hopkins University Press, 2009. Pp 241-254.
- Hoffman EP. Skipping toward personalized molecular medicine. N Engl J Med. 2007 Dec 27;357(26):2719-22.
- Yokota T, Takeda S, Lu QL, Partridge TA, Nakamura A, Hoffman EP. A renaissance for antisense oligonucleotide drugs in neurology: exon skipping breaks new ground. Arch Neurol. 2009 Jan;66(1):32-8.
- Yokota T, Lu QL, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E. Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Ann Neurol. 2009 Jun;65(6):667-76.
- Yokota T, Hoffman E, Takeda S. Antisense oligo-mediated multiple exon skipping in a dog model of Duchenne muscular dystrophy. Methods Mol Biol. 2011;709:299-312.
- Hoffman EP, Bronson A, Levin AA, Takeda S, Yokota T, Baudy AR, Connor EM. Restoring dystrophin expression in duchenne muscular dystrophy muscle progress in exon skipping and stop codon read through. Am J Pathol. 2011 Jul;179(1):12-22.
Muscular dystrophy: Research projects focus on a number of topics within the muscular dystrophies. We are interested in improving diagnosis through application of emerging technologies, and are looking towards whole genome or massively parallel targeted re-sequencing as approaches that may facilitate and expedite patient diagnosis. We have many projects in molecular pathophysiology, where we strive to understand the molecular and cellular mechanisms leading to progressive muscle weakness and disability. Through an increased understanding of disease progression, we can then target these pathways with drugs and other interventions, to slow or stop the disease. There is also a strong interest in therapeutic development, and we work closely with other pre-clinical and clinical faculty in ISB to facilitate novel therapeutics. Active research projects include exon skipping research, non-hormonal steroid drug development, and multidrug approaches towards halting disease progression.
Genetics of muscle variation: Muscle could be argued to be one of the most responsive to the environment; it changes character based on types of activity patterns, changes its interactions with motor neurons, and can serve as a protein reservoir in times of food deprivation. The remodeling of muscle is also highly dependent on an individual’s genetic background (polymorphisms). A goal of the laboratory has been to identify genetic modifiers of muscle structure and function, both in normal individuals (e.g. response to resistance training), and in muscular dystrophy patients (e.g. severe vs. mild onset and progression, or response to steroids). The laboratory has completed GWAS studies of response to resistance training, and is working to characterize the molecular function of these polymorphisms, and studying them as disease modifiers of muscular dystrophy.
Personalized medicine: An oft-stated deliverable of genetic and genomic research is ‘personalized medicine’, where therapeutics can be customized to an individual’s genetic background. However, there are few examples of achieving this ‘deliverable’, and certainly no implementations on a public health scale. Type 2 diabetes can be considered the most common and most disabling public health problems, and incidence is rising rapidly. Each of the hallmark metabolic syndrome features leading to metabolic syndrome (central obesity, poor blood lipid profiles, high blood pressure, and insulin resistance) have strong genetic components (typically 50-60%). If the promise of personalized medicine can be realized, type 2 diabetes may be the best target, yet the personalized interventions are best done in children or young adults. The laboratory has a series of studies underway, often in collaboration with other groups throughout the US and Canada, to provide a proof of principle of personalized medicine as applied to prevention of type 2 diabetes in children and young adults.
Link to pubmed publications: http://www.ncbi.nlm.nih.gov/pubmed/?term=hoffman+ep
- Clinical and Translational Research
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.