Valerie HuProfessor of Biochemistry and Molecular Medicine
Associate Professor of Genetics (Secondary)
Office Phone: 202-994-8431
Department: Biochemistry and Molecular Medicine
- BS, University of Hawaii, 1972
- PhD, California Institute of Technology, 1977
The long-term goals of my laboratory are personalized diagnosis and treatment of autism spectrum disorders (ASD). We aim to achieve these goals by developing a better understanding of the underlying biology giving rise to different manifestations of autism through the identification of altered genes, pathways, and gene regulatory mechanisms specific to the different subtypes of ASD. As shown by our published studies on individuals with ASD, we have succeeded in identifying genes, metabolic/signaling pathways, and epigenetic mechanisms (both DNA methylation and microRNA expression) involved in ASD by reducing the clinical heterogeneity among subjects for transcriptomic, genetic and epigenetic analyses. We accomplish heterogeneity reduction either by using diagnostically discordant monozygotic twins and siblings in our studies or by dividing the ASD population into more homogeneous subgroups based on similar symptomatic profiles. The latter technique has proven to be especially useful in identifying subtype-dependent gene expression differences among groups of unrelated individuals with ASD relative to controls as well as subtype-dependent genetic variants (SNPs) and linkage loci. In both expression and genetic analyses, a number of shared genes/SNPs were also identified, demonstrating some of the expected biological commonality among the ASD subtypes. Interestingly, the shared SNPs exhibited distinctly different odds ratios in the different subtypes, demonstrating that the subtypes are genetically distinct in relation to these SNPs. Thus, a systems approach to ASD using integrative genomics coupled with phenotyping of subjects has led to the discovery of novel candidate genes relevant to pathobiological processes involved in ASD as well as to the identification of potential diagnostic biomarkers at multiple levels: gene expression, microRNA, DNA methylation, and genetics. One of the novel genes identified through our studies is retinoic acid-related orphan receptor alpha (RORA) which is a nuclear hormone receptor that not only regulates many other genes that are implicated in the pathobiology of ASD, but also is oppositely regulated by male and female hormones in a manner that suggests its contribution to the male bias in ASD. Ongoing studies are continuing to examine mechanisms of pathogenesis involving dysregulation of RORA as well as gene-environment interactions that elevate risk for ASD.
For more on Dr. Hu’s Autism research, watch the video.
View publications by this faculty member from January 1, 2013 - present
Hu, V.W. (2013) From Genes to Environment: Using integrative genomics to build a “systems level” understanding of autism. Invited review, Child Development, 84(1):89-103. PMID: 22497667
Hu, V.W. (2013) The Expanding Genomic Landscape of Autism Spectrum Disorders: Discovering the “Forest” Beyond the “Trees”, Invited perspective article, Future Neurology, 8(1):29-42.
Sarachana, T. and Hu, V.W. (2013) Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder. Molecular Autism, 4(1):14. PMID: 23697635
Talebizadeh, Z., Arking, D.E., and Hu, V.W. (2013) A novel stratification method in linkage studies to address inter and intra family heterogeneity in autism. PLoS ONE, 8(6):e67569.
Hu, V.W. and Lai, Y. (2013) Developing a predictive gene classifier for autism spectrum disorders based upon differential gene expression profiles of phenotypic subgroups. North American Journal of Medicine and Science, 6(3):107-116. Download PDF
Sarachara, T. and Hu, V.W. (2013) Differential recruitment of coregulators to the RORA promoter adds another layer of complexity to gene (dys)regulation by sex hormones in autism. Molecular Autism, in press.
Hu, V.W. (2012) Is retinoic acid-related orphan receptor-alpha (RORA) a target for gene-environment interactions contributing to autism? Neurotoxicology, 33(6):1434-35. PMID: 22967355
Hu, V.W. (2012) Subphenotype-dependent disease markers for diagnosis and personalized treatment of autism spectrum disorders. Invited Review, Disease Markers, 33(5):277-88. PMID: 22960334 Download PDF
Sarachana, T., Xu, M., Wu, R.-C., and Hu, V.W. (2011) Sex hormones in autism: Androgens and estrogens differentially and reciprocally regulate RORA, a novel candidate gene for autism PLoS ONE, 6(2): e17116. PMID: 21359227
Hu, V.W., Addington, A., and Hyman, A. (2011) Novel Autism Subtype-dependent Genetic Variants are Revealed by Quantitative Trait and Subphenotype Association Analyses of Published GWAS Data PLoS ONE 6(4):e19067. PMID: 21556359
Hu, V.W. (2011) A Systems Approach towards an Understanding, Diagnosis, and Personalized Treatment of Autism Spectrum Disorders. Invited editorial, Pharmacogenomics, 12(9):1235-38. PMID: 21919600
Nguyen, A., Rauch, T.A., Pfeifer, G.P., and Hu, V.W. (2010) Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J., 24(8):3036-51. PMID: 20375269
Sarachana, T., Zhou, R., Chen, G., Manji, H.K., and Hu, V.W. (2010) Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders (ASD) by microRNA expression profiling of lymphoblastoid cell lines. Genome Medicine, 2(4):23 PMID: 20374639
Hu, V.W. and Steinberg, M.E. (2009) Novel clustering of items from the Autism Diagnostic Interview-Revised to define phenotypes within autism spectrum disorders. Autism Research 2:67-77. PMID: 19418574; PMCID: PMC2737479
Hu, V.W., Sarachana, T., Kim, K.S., Nguyen, A., Kulkarni, S., Steinberg, M.E., Luu, T., Lai, Y., and Lee, N.H. (2009) Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: Evidence for circadian rhythm dysfunction in severe autism. Autism Research 2:78-97. PMID: 19455643; PMCID: PMC2737477
Hu, V.W., Nguyen, A., Kim, K.S., Steinberg, M.E., Sarachana, T., Scully, M., Soldin, S.J., Luu, T., and Lee, N.H. (2009) Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: Altered pathways in neuronal development and steroid biosynthesis. PLoS ONE 4(6): e5775. PMID: 19492049; PMCID: PMC2685981
Hu, V.W., Frank, B.C., Heine, S., Lee, N.H., and Quackenbush, J. (2006) Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes. BMC Genomics 7:118. PMID: 16709250
Additional publications published before January 1, 2013 may be available within Himmelfarb Library's database.