Javascript must be enabled to use this form.

View Profile	Home Browse Faculty Facility Research Consortia Training Grants Courses Search Support About rSp Help and FAQ's Contact Us	GCC Home
Faculty Profile Last Modified Time: 02:29:36 PM Thu, 7 Mar 2024   Contact Information James Lupski Associated Profiles  The Cullen Foundation Endowed Chair in Molecular Genetics, Professor, Molecular and Human Genetics & Pediatrics, Baylor College of Medicine   One Baylor Plaza, Room No.: 604B    jlupski@bcm.edu     (713) 798-6530    Web Link    Molecular Genetics of Charcot-Marie-Tooth Disease and Related Inherited Neuropathies, Molecular Mechanisms for Human DNA Rearrangements, Genomic Disorders, Copy Number Variation (CNV) and Disease, Human Genome Analysis    Associated Profiles Research and Expertise Affiliations Appointments  Research and Expertise Research Interests   Our laboratory is interested in determining the molecular mechanisms for disease using human genetic approaches to investigate clinical phenotypes. A major focus is the molecular genetics of Charcot-Marie-Tooth (CMT) disease and related inherited demyelinating peripheral neuropathies. The predominant form of CMT results from an inherited DNA rearrangement and a gene dosage effect. The 1.5 Mb tandem CMT1A duplication arises from recombination at flanking ~24 kb repeat sequences (CMT1A-REPs). The reciprocal recombination results in a 1.5 Mb deletion and a clinically distinct dominant demyelinating neuropathy: hereditary neuropathy with liability to pressure palsies (HNPP). The CMT1A duplication and HNPP deletion document the first examples in humans of Mendelian syndromes resulting from the reciprocal products of unequal exchange involving large intrachromosomal segments. CMT1A and HNPP result from altered copy number of PMP22 and constitute an unprecedented model of phenotypic consequences resulting from a range of possible gene dosages in humans. Current efforts are focused on identifying mutations in other genes that result in inherited neuropathy phenotypes and investigating molecular mechanisms, such as nonsense-mediated decay, for genotype/phenotype correlations. To date, more than 30 CMT genes have been identified. Genes for structural proteins (PMP22, MPZ), a gap junction protein (Cx32), transcription factors (EGR2, SOX10, SIMPLE), signal transduction molecules, and proteins important for axonal transport have been associated with CMT or related neuropathy. One further focus is to investigate small molecules that may affect protein folding as a potential therapeutic approach to selected forms of neuropathy. Additional efforts are aimed at determining the molecular mechanism for contiguous gene syndromes. An extensive clinical description is underway to study patients with deletion 17p11.2 or the Smith-Magenis syndrome (SMS). The SMS common deletion occurs by nonallelic homologous recombination (NAHR) of a flanking low-copy repeat (LCR) gene cluster (SMS-REP) and the reciprocal recombination results in duplication of this region. Results from other laboratories suggest that a similar mechanism is responsible for other interstitial microdeletion syndromes. Current efforts focus on using mouse models to delineate the gene(s) responsible for the phenotype and study the phenotypic consequences of systematic alterations in copy number for dosage sensitive genes. Studies on both CMT1A and SMS have delineated the concept of genomic disorders-structural features of the genome which can lead to DNA rearrangements and human disease traits. Other human genetic disease gene mapping research involves collaborative efforts with Dr. Richard A. Lewis to determine the molecular genetic bases of retinopathies including Stargardt disease: Studies of Bardet-Biedl syndrome (BBS) have suggested a novel genetic mechanism we have termed "triallelic inheritance" for this genetically heterogeneous condition. In some families, a combination of three distinct alleles from two (or more) loci appear necessary and sufficient for trait manifestation. Triallelic inheritance may represent a transmission model that bridges classic Mendelian disorders with complex traits.  Publications/Creative Works Click here to search for this faculty member's publications on PubMed.  Affiliations  Research Consortia Gulf Coast Cluster for Single Cell Omics  Appointments Title Department / School Institution Professor Molecular and Human Genetics, Pediatrics Baylor College of Medicine The Cullen Foundation Endowed Chair Molecular Genetics Baylor College of Medicine

powering - The Partnership
Important Disclaimer: The responsibility for the accuracy of the information contained on these pages lies with the authors and user providing such information.