Research Topics
Genomes and Genes
| Susan A SlaugenhauptSummaryAffiliation: Harvard University Country: USA Publications
| Collaborators
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Detail Information
Publications
Familial dysautonomiaSusan A Slaugenhaupt
Harvard Institute of Human Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
Curr Opin Genet Dev 12:307-11. 2002..IKAP, the IKBKAP-encoded protein, is a member of the recently identified human Elongator complex. The major FD mutation is a splice mutation that results in aberrant tissue-specific mRNA splicing...- Genetics of familial dysautonomia. Tissue-specific expression of a splicing mutation in the IKBKAP geneSusan A Slaugenhaupt
Harvard Institute of Human Genetics, Harvard Medical School, Boston, MA 02115, USA
Clin Auton Res 12:I15-9. 2002 - The molecular basis of mucolipidosis type IVSusan A Slaugenhaupt
Harvard Institute of Human Genetics, Harvard Medical School, Boston, MA 02115, USA
Curr Mol Med 2:445-50. 2002..elegans mucolipin-1 homolog allow us to begin to speculate about the role of mucolipin-1 in diverse cellular processes... 
A humanized IKBKAP transgenic mouse models a tissue-specific human splicing defectMatthew M Hims
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Genomics 90:389-96. 2007..Last, these mice will permit direct studies of tissue-specific splicing and the identification of regulatory factors that play a role in complex gene expression...- Lysosomal exocytosis is impaired in mucolipidosis type IVJanice M LaPlante
Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Mol Genet Metab 89:339-48. 2006..Further, we show that transfection with wild type MLN1 cDNA rescues exocytosis, suggesting the possibility of treatments based on the restoration of this crucial cellular function... - Loss of mouse Ikbkap, a subunit of elongator, leads to transcriptional deficits and embryonic lethality that can be rescued by human IKBKAPYei Tsung Chen
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Mol Cell Biol 29:736-44. 2009..For the first time, we demonstrate that IKAP is crucial for both vascular and neural development during embryogenesis and that protein function is conserved between mouse and human... - New locus for autosomal dominant mitral valve prolapse on chromosome 13: clinical insights from genetic studiesFrancesca Nesta
Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
Circulation 112:2022-30. 2005..Early recognition of gene carriers could potentially enhance the clinical evaluation of patients at risk of full expression, with the ultimate aim of developing interventions to reduce progression... - Therapeutic potential and mechanism of kinetin as a treatment for the human splicing disease familial dysautonomiaMatthew M Hims
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
J Mol Med (Berl) 85:149-61. 2007..Lastly, we highlight the potential of kinetin for the treatment of other human splicing disorders by showing correction of a splicing defect in neurofibromatosis... - Functional links between mucolipin-1 and Ca2+-dependent membrane trafficking in mucolipidosis IVJanice M LaPlante
Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Biochem Biophys Res Commun 322:1384-91. 2004.... - Specific correction of a splice defect in brain by nutritional supplementationRanjit S Shetty
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, 185 Cambridge Street, CPZN 5254, Boston, MA 02114, USA
Hum Mol Genet 20:4093-101. 2011.... 
Functional multimerization of mucolipin channel proteinsCyntia Curcio-Morelli
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
J Cell Physiol 222:328-35. 2010..Our data shows for the first time that TRPMLs form distinct functional channel complexes. Homo- and hetero-multimerization of TRPMLs may modulate channel function and biophysical properties, thereby increasing TRPML functional diversity...- The cation channel mucolipin-1 is a bifunctional protein that facilitates membrane remodeling via its serine lipase domainJanice M LaPlante
Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
Exp Cell Res 317:691-705. 2011..MLN1 is absent or mutated in patients with mucolipidosis IV (MLIV), a lysosomal disorder with devastating neurological and other consequences. This study provides potential insight into the pathophysiology of MLIV... - Chaperone-mediated autophagy is defective in mucolipidosis type IVBhuvarahamurthy Venugopal
Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
J Cell Physiol 219:344-53. 2009..It is also possible that TRPML1 channel activity may be required for CMA. Understanding the role of TRPML1 in CMA will undoubtedly help to characterize the pathogenesis of MLIV... - Weak definition of IKBKAP exon 20 leads to aberrant splicing in familial dysautonomiaEl Cherif Ibrahim
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Hum Mutat 28:41-53. 2007.... - Macroautophagy is defective in mucolipin-1-deficient mouse neuronsCyntia Curcio-Morelli
Center for Human Genetic Research, Massachusetts General Hospital Harvard Medical School, Boston, MA 02114, USA
Neurobiol Dis 40:370-7. 2010..This study describes, for the first time, a defect in macroautophagy in mucolipin-1-deficient neurons, which corroborates recent findings in MLIV fibroblasts and provides new insight into the neuronal pathogenesis of this disease... - Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomiaMath P Cuajungco
Harvard Institute of Human Genetics, Harvard Medical School, Boston, MA, USA
Am J Hum Genet 72:749-58. 2003..Therefore, exploration of methods to increase the WT:MU IKBKAP transcript ratio in the nervous system offers a promising approach for developing an effective therapy for patients with FD... - Neurologic, gastric, and opthalmologic pathologies in a murine model of mucolipidosis type IVBhuvarahamurthy Venugopal
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Am J Hum Genet 81:1070-83. 2007..In addition, this model provides an invaluable resource for testing treatment strategies and potential therapies aimed at preventing or ameliorating the abnormal lysosomal storage in this devastating neurological disorder... - The corticotropin-releasing hormone gene and behavioral inhibition in children at risk for panic disorderJordan W Smoller
Department of Psychiatry, Massachusetts General Hospital, Boston 02114, USA
Biol Psychiatry 57:1485-92. 2005..To evaluate this further, we genotyped additional families for this marker and a panel of markers encompassing the CRH locus... - Rescue of a human mRNA splicing defect by the plant cytokinin kinetinSusan A Slaugenhaupt
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
Hum Mol Genet 13:429-36. 2004..Further, kinetin should be explored as a treatment for increasing the level of normal IKAP in FD, and for other splicing disorders that may share a similar mechanism... - Molecular genetics of mitral valve prolapseRobert A Levine
Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
Curr Opin Cardiol 22:171-5. 2007..It is associated with important mitral regurgitation requiring surgical repair and other clinical complications. Genetic studies can provide clues to mechanism and therapy... - Association of a genetic marker at the corticotropin-releasing hormone locus with behavioral inhibitionJordan W Smoller
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Biol Psychiatry 54:1376-81. 2003..Transgenic mice overexpressing CRH exhibit BI-like behaviors, implicating this gene in the development of the phenotype... - The GPR54 gene as a regulator of pubertyStephanie B Seminara
Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA
N Engl J Med 349:1614-27. 2003..We conducted studies in humans and mice to identify the genetic factors that determine the onset of puberty... - Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathwayJanice M LaPlante
Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA
FEBS Lett 532:183-7. 2002..With its Ca(2+) permeability and modulation by [Ca(2+)], MLN1 could play a major role in Ca(2+) transport regulating lysosomal exocytosis and potentially other phenomena related to the trafficking of late endosomes and lysosomes... - Enzymatic mechanisms in corneal ulceration with specific reference to familial dysautonomia: potential for genetic approachesM Elizabeth Fini
Vision Research Laboratories, New England Eye Center, Tufts University School of Medicine and Tufts Center for Vision Research, Boston, Massachusetts, USA
Adv Exp Med Biol 506:629-39. 2002 - A locus for autosomal dominant mitral valve prolapse on chromosome 11p15.4Lisa A Freed
The Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Am J Hum Genet 72:1551-9. 2003..The discovery of genes involved in the pathogenesis of this common disease is crucial to understanding the marked variability in disease expression and mortality seen in MVP... - IKBKAP mRNA in peripheral blood leukocytes: a molecular marker of gene expression and splicing in familial dysautonomiaGabrielle Gold-von Simson
Department of Pediatrics, New York University School of Medicine, New York, New York 10016, USA
Pediatr Res 63:186-90. 2008..Levels of IKBKAP mRNA in peripheral blood leukocytes can be used to assess molecular response to therapies aimed at enhancing exon 20 inclusion and increasing cellular levels of ELP1/IKAP... - Transcription impairment and cell migration defects in elongator-depleted cells: implication for familial dysautonomiaPierre Close
Laboratory of Medical Chemistry and Human Genetics, Center for Biomedical Integrative Genoproteomics, University of Liege, Belgium
Mol Cell 22:521-31. 2006..These results indicate that defects in Elongator function affect transcriptional elongation of several genes and that the ensuing cell motility deficiencies may underlie the neuropathology of FD patients... - Caenorhabditis elegans functional orthologue of human protein h-mucolipin-1 is required for lysosome biogenesisSebastian Treusch
Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA
Proc Natl Acad Sci U S A 101:4483-8. 2004..Finally, we propose a model that relates the lysosome biogenesis defect in the absence of CUP-5/h-mucolipin-1 to cellular phenotypes in worms and in humans... - Identification of the first non-Jewish mutation in familial DysautonomiaMaire Leyne
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, USA
Am J Med Genet A 118:305-8. 2003..In light of this fact, the diagnostic criteria for FD must be expanded. Furthermore, in order to ensure carrier identification in all ethnicities, this mutation must now be considered when screening for FD... - Of splice and men: what does the distribution of IKAP mRNA in the rat tell us about the pathogenesis of familial dysautonomia?Eva Mezey
Basic Neuroscience Program, NINDS, NIH, Building 36, Room 3D 06, Bethesda, MD 20892, USA
Brain Res 983:209-14. 2003..The mRNA is widely distributed. Highest levels are in the nervous system, but substantial amounts are also present in peripheral organs... - Fludrocortisone in patients with familial dysautonomia--assessing effect on clinical parameters and gene expressionFelicia B Axelrod
Dept of Pediatrics, New York University School of Medicine, New York, NY, USA
Clin Auton Res 15:284-91. 2005..Our data suggest that fludrocortisone has clinical efficacy despite negative in vitro observations on gene expression...