Sarah H. Elsea, Ph.D.
Associate Professor of Molecular and Human Genetics
Director, Biochemical Genetics Laboratory, BCM Medical Genetics Laboratories
B.S. Missouri State University, 1990
Ph.D. Vanderbilt University, 1994
Postdoctoral fellow, Vanderbilt University, 1995
Postdoctoral fellow, Baylor College of Medicine, 1998
American Board of Medical Genetics: Clinical Biochemical Genetics
Member, American Society of Human Genetics
Member, American College of Medical Genetics
Member, Society for Inherited Metabolic Disorders
Society for the Study of Inborn Errors of Metabolism
My overall goal is to understand the biochemical mechanisms and molecular pathways underlying human genetic disease. The current work in my laboratory is focused on the genetic analysis of neurodevelopmental disorders complicated by obesity and circadian rhythm defects and includes disorders involving autism, intellectual disability, seizures, and behavioral phenotypes. A primary focus of our work is the analysis of genomic disorders, wherein deletion or duplication of a portion of the genome is involved in the etiology of the syndrome, altering gene dosage. These disorders include Smith-Magenis syndrome (SMS), Potocki-Lupski syndrome (PTLS), 2q23.1 deletion syndrome, 2q23.1 duplication syndrome, 2q37.3 deletion syndrome (BDMR), and others. Our goals are improved diagnosis, enhanced understanding of the phenotypes and a working knowledge of the molecular relationships among neurodevelopmental disorders. The lab identified the causative genes for several of these syndromes, including SMS (RAI1), BDMR (HDAC4), and the 2q23.1 del/dup disorders (MBD5).
We use a multidisciplinary approach to understand the molecular and cellular basis of these pleiotropic disorders, including mouse, frog, zebrafish and human cellular models, such as induced pluripotent stem cells. Our current studies are focused toward understanding the molecular and cellular relationships between and among a subgroup of neurodevelopmental disorders with overlapping phenotypes. These disease genes include RAI1, MBD5, HDAC4, and TCF4, among others. The common pathways affected in these disorders include circadian rhythm, metabolic, and developmental gene networks that may be targets for therapeutic intervention and are currently being investigated. For example, one of the hallmark features of Smith-Magenis syndrome is the circadian rhythm defect. Our recent work has shown that RAI1 directly regulates the CLOCK gene, a master regulator of circadian rhythm, providing strong evidence for molecular and cellular etiology behind the sleep phenotype and identifying a pathway that can be therapeutically targeted.
While most of the work in our lab has a molecular basis, we have a keen interest in providing the parents, caregivers, and siblings of individuals with neurodevelopmental syndromes with the tools they need to maintain healthy families. Our work with families is focused toward understanding the effects that caregivers experience due to caring for individuals with Smith-Magenis, Williams, or Down syndromes, as well as the sibling dynamics in families with both typically developing children and a child with a neurodevelopmental syndrome. These studies have revealed the significant impact living with and/or caring for an individual with a neurodevelopmental disorder can have on a typically developing person and show that families are doing very well despite the high prevalence of anxiety and depression among both mothers and fathers. Our data also show that while younger typically developing siblings may have some difficulties, adult siblings are doing very well, with many choosing careers in education or healthcare of individuals with developmental disabilities.
- Mullegama SV, Rosenfeld JA, Orellana C, van Bon BW, Halbach S, Repnikova EA, Brick L, Li C, Dupuis L, Rosello M, Aradhya S, Stavropoulos DJ, Manickam K, Mitchell E, Hodge JC, Talkowski ME, Gusella JF, Keller K, Zonana J, Schwartz S, Pyatt RE, Waggoner DJ, Shaffer LG, Lin AE, de Vries BB, Mendoza-Londono R, Elsea SH (2013). Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder. Eur. J. Hum. Genet.. doi: 10.1038/ejhg.2013.67. [Epub ahead of print] PubMed PMID: 23632792
- Moshier MS, York TP, Silberg JL, Elsea SH (2012). Siblings of individuals with Smith-Magenis syndrome: an investigation of the correlates of positive and negative behavioural traits. J. Intellect. Disabil. Res. 56(10):996-1007. PubMed PMID: 22672270
- Williams SR, Zies D, Mullegama SV, Grotewiel MS, Elsea SH (2012). Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity. Am. J. Hum. Genet. 90(6): 941-9. PubMed PMID: 22578325
- Talkowski ME, Mullegama SV, Rosenfeld JA, van Bon BW, Shen Y, Repnikova EA, Gastier-Foster J, Thrush DL, Kathiresan S, Ruderfer DM, Chiang C, Hanscom C, Ernst C, Lindgren AM, Morton CC, An Y, Astbury C, Brueton LA, Lichtenbelt KD, Ades LC, Fichera M, Romano C, Innis JW, Williams CA, Bartholomew D, Van Allen MI, Parikh A, Zhang L, Wu BL, Pyatt RE, Schwartz S, Shaffer LG, de Vries BB, Gusella JF, Elsea SH (2011). Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder. Am. J. Hum. Genet. 89(4): 551-63. PubMed PMID: 21981781
- Burns B, Schmidt K, Williams SR, Kim S, Girirajan S, Elsea SH (2010). Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome. Hum. Mol. Genet. 19(20): 4026-42. PubMed PMID: 20663924
- Williams SR, Aldred MA, Der Kaloustian VM, Halal F, Gowans G, McLeod DR, Zondag S, Toriello HV, Magenis RE, Elsea SH (2010). Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. Am. J. Hum. Genet. 87(2): 219-28. PubMed PMID: 20691407
- Williams SR, Mullegama SV, Rosenfeld JA, Dagli AI, Hatchwell E, Allen WP, Williams CA, Elsea SH (2010). Haploinsufficiency of MBD5 associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures. Eur. J. Hum. Genet. 18(4): 436-41. PubMed PMID: 19904302
- Williams SR, Girirajan S, Tegay D, Nowak N, Hatchwell E, Elsea SH (2010). Array comparative genomic hybridisation of 52 subjects with a Smith-Magenis-like phenotype: identification of dosage sensitive loci also associated with schizophrenia, autism, and developmental delay. J. Med. Genet. 47(4): 223-9. PubMed PMID: 19752160
- Foster RH, Kozachek S, Stern M, Elsea SH (2010). Caring for the caregivers: an investigation of factors related to well-being among parents caring for a child with Smith-Magenis syndrome. J. Genet. Couns. 19(2): 187-98. PubMed PMID: 20151318
- Girirajan S, Elsea SH (2009). Abnormal maternal behavior, altered sociability, and impaired serotonin metabolism in Rai1-transgenic mice. Mamm. Genome 20(4): 247-55. PubMed PMID: 19319603
- Girirajan S, Truong HT, Blanchard CL, Elsea SH (2009). A functional network module for Smith-Magenis syndrome. Clin. Genet. 75(4): 364-74. PubMed PMID: 19236431
- Girirajan S, Patel N, Slager RE, Tokarz ME, Bucan M, Wiley JL, Elsea SH (2008). How much is too much? Phenotypic consequences of Rai1 overexpression in mice. Eur. J. Hum. Genet. 16(8): 941-54. PubMed PMID: 18285828
Sarah H. Elsea, Ph.D.
Baylor College of Medicine
Dept of Molecular and Human Genetics
One Baylor Plaza, MS NAB2015
Houston, TX, 77030, U.S.A.