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Faculty Profile Last Modified Time: 10:28:16 AM Fri, 17 Apr 2020   Contact Information Richard Sifers Associated Profiles  Professor, Pathology & Immunology, Director of Operations, Center for Drug Discovery, Baylor College of Medicine     rsifers@bcm.edu     713-798-3169    Web Link    PCR, Gel Electrophoresis, DNA, Western Blot Analysis, Gene Expression, Cloning, Cancer Biology, Protein Purification, Molecular Biology, Sequencing, Genomics, Proteins, Genetics, Molecular Cloning, Cell Biology, Biochemistry, Enzymes, Genetic Engineering    Associated Profiles Research and Expertise Affiliations Appointments  Research and Expertise Research Interests   Genetic information is inherited as DNA and stored in the nucleus. Despite this important role, the encoded proteins are responsible for performing most of the catalytic and structural functions that take place in living cells. Importantly, protein folding and quality control systems comprise two branches of a post-translational gene expression checkpoint. Their contribution to disease pathogenesis is illustrated by their conspicuous involvement in numerous loss-of-function and gain-of-toxic function disorders. Arguably, protein biosynthetic quality control is best understood in the secretory pathway where the processing of asparagine-linked oligosaccharides functions to orchestrate the elimination of numerous aberrant glycoproteins unable to acquire structural maturation. In particular, we have discovered that modification of the asparagine-linked appendage by endoplasmic reticulum mannosidase I (ERManI), in combination with non-native protein structure, is responsible for generating the degradation signal. Importantly, the concentration of ERManI controls the rate of substrate degradation by controlling the rate at which the degradation signal is formed. However, neither the mechanism by which the ERManI concentration is controlled or its contribution to disease pathogenesis is fully understood. We have begun to dissect this key regulatory pathway and have shown that the ERManI concentration is controlled at both translational and post-translational levels. Furthermore, preliminary data imply that an elevated ERManI concentration plays a protective role against the development of liver disease associated with plasma alpha1-antitrypsin deficiency, presumably by hindering the accumulation of PI Z polymers in the ER of liver hepatocytes. Likewise, an apparent failure to up-regulate the ERManI concentration coincides with the development of the early-onset form of the disorder. The immediate goals are to further dissect the mechanism of human ERManI regulation and delineate its participation in the etiology of the liver disease. The long term goal is to demonstrate how a core element of the glycoprotein quality control machinery can function as a disease modifier, possible diagnostic marker, and potential site for therapeutic intervention.  Publications/Creative Works Click here to search for this faculty member's publications on PubMed.  Affiliations  Research Consortia John S. Dunn GCC for Chemical Genomics  Training Grants Training in Precision Environmental Health Sciences (TPEHS)  Appointments Title Department / School Institution Professor Pathology & Immunology Baylor College of Medicine Director of Operations Center for Drug Discovery Baylor College of Medicine

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