Alan Herbert, MB.ChB., Ph.D.
Associate Professor of Pharmacology and Neurology
Department of Pharmacology
Lab Page: Laboratory of Brain Genomics
Ph.D.: University of Auckland
MB.ChB.: University of Auckland
Alan Herbert, MB.ChB., PhD received his medical degree from the University of Auckland in 1979 and completed his PhD in Immunobiology and worked at MIT in the laboratory of Dr. Alexander Rich. He discovered the first evidence for the existence of high affinity proteins specific for the left-handed Z-DNA conformation. This work lead to the isolation of the RNA-editing enzyme called double-stranded RNA adenosine deaminase (ADAR1) and the characterization of its Zα Z-DNA binding fold . This finding has paved the way for other investigators to study the role of Z-DNA in vaccinia infection, in the interferon response and enabled crystallographic studies to reveal the structure of Z-RNA and B-Z DNA junctions at atomic resolution. Dr Herbert returned to his medical roots in 2000when he joined the Framingham Heart Study at Boston University. With the imminent publication of the human genome sequence and the cataloguing of genetic differences between individuals, the Framingham Study with data collected on 10,000 individuals over two generations for over 50 years offered a great opportunity to apply newly developed methods for identifying those genetic variants that determine human individuality and disease risk. Dr Herbert was successful in bringing this work to fruition with his publication in Science in 2006 with coauthors from different institutions. This study encouraged the National, Heart Lung and Blood Institute to invest heavily in further studies of this type, including the SHARe to study the entire Framingham Heart Study Cohort, including the recently recruited third generation. His laboratory also has interacted with groups working on Parkinson’s Disease and osteoporosis. He is currently collaborating with the Howard University Family Study to perform a high density genome scan of an African American population. Dr Herbert has over 50 peer-reviewed publications. He has extensive experience in working with and analyzing the large datasets associated with genome-wide scans from populations with diverse origins. Current research interests include the genetics of obesity and schizophrenia, the role of somatic mutation in complex disease and events mediated by non-coding RNAs.
Dr Herbert also serves as a consultant to Coriell Institute for Medical Research in establishing the Coriell Personalized Medicine Project. As community-service, Dr. Herbert works with Operation Smile where he is helping establish the Operation Smile International Family Study to study the genetic factors that increase risk of cleft lip and plate.
Herbert, A. A neural architecture based on Hadamard designs. The Open Neuroscience Journal, 2011. In press.
Herbert, A. et al. Open-access database of candidate associations from a genome-wide SNP scan of the Framingham Heart Study. Nat Genet 39, 135-6 (2007).
Herbert, A. et al. A common genetic variant is associated with adult and childhood obesity. Science 312, 279-83 (2006).
Herbert, A. et al. BMI modifies associations of IL-6 genotypes with insulin resistance: the Framingham Study. Obesity (Silver Spring) 14, 1454-61 (2006).
Van Steen, K. et al. Genomic screening and replication using the same data set in family-based association testing. Nat Genet 37, 683-91 (2005).
Herbert, A. et al. The -174 IL-6 GG genotype is associated with a reduced risk of type 2 diabetes mellitus in a family sample from the National Heart, Lung and Blood Institute’s
Herbert, A. The four Rs of RNA-directed evolution. Nat Genet 36, 19-25 (2004).
Herbert, A., Wagner, S. & Nickerson, J. A. Induction of protein translation by ADAR1 within living cell nuclei is not dependent on RNA editing. Mol Cell 10, 1235-46 (2002).
Herbert, A. & Rich, A. The role of binding domains for dsRNA and Z-DNA in the in vivo editing of minimal substrates by ADAR1. Proc Natl Acad Sci U S A 98, 12132-7 (2001).
Schwartz, T., Rould, M. A., Lowenhaupt, K., Herbert, A. & Rich, A. Specific Recognition of left-handed Z-DNA: Co-crystal structure of the Za DNA recognition motif of ADAR1 at 2.1Å resolution. Science 284, 1841-1845 (1999).
Herbert, A., Kim, Y.-G., Alfken, J., Nishikura, K. & Rich, A. A Z-DNA binding domain from the human editing enzyme dsRNA adenosine deaminase. Proceedings of the National Academy of Science, USA 94, 12875-12879 (1997).