The Section on Molecular Dysmorphology studies the molecular, biochemical, and cellular processes that underlie genetic disorders resulting from impaired cholesterol homeostasis and lysosomal dysfunction.  Inborn errors of cholesterol synthesis, such as Smith-Lemli-Opitz syndrome (SLOS), result in congenital malformation/cognitive impairment disorders.  Lysosomal diseases such as Niemann-Pick disease, type C (NPC) and CLN3 disease (Juvenile Batten disease) result in progressive neurodegeneration. Our research group uses basic, translational, and clinical research approaches with the ultimate goal of developing and testing therapeutic interventions for rare genetic disorders. Preclinical models being used to gain insight into pathological mechanisms include induced pluripotent stem cells, zebrafish and mouse models. Induced pluripotent stem cells are being used in high throughput drug screens and mouse models are being used to test for efficacy. In collaboration with NHGRI laboratories we are investigating gene therapy.   Our clinical research group maintains ongoing natural history trials of SLOS, NPC1 and CLN3-disease.  For all three disorders we have a large collection of biomaterials (cell lines, urine, blood, cerebral spinal fluid) from well phenotyped individuals with these disorders.  This unique biomaterial collection is being used for biomarker identification and validation.  Multiple therapeutic trials have been conducted for SLOS and NPC1, and we are initiating therapeutic trials for CLN3 disease. In support of a project with the National Center for Advancing Translational Sciences (NCATS), our research group has been involved in a multicenter trial of creatine transporter deficiency.

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