Russell DeBose-Boyd, PhD (UT Southwestern Medical Center) Webinar

Russell DeBose-Boyd, PhD (UT Southwestern Medical Center) Webinar

Butler Seminar Series

Event Date/Location

November 23, 2020 - 12:00 pm to 1:00 pm
Thomas Laboratory


  • Russell DeBose-Boyd

    Professor, Beatrice and Miguel Elias Distinguished Chair in Biomedical Science Department of Molecular Genetics, University of Texas Southwestern Medical Center
    University of Texas, Southwestern Medical School

    Dr. DeBose-Boyd was born and raised in the small rural southeastern Oklahoma town of Boswell. He completed undergraduate studies at Southeastern Oklahoma State University, where he participated in the Minority Biomedical Research Support program and . obtained a Bachelor of Science degree in Chemistry with minors in Mathematics and Biology. Soon after completion of undergraduate studies, Dr. DeBose-Boyd joined the laboratory of Richard D. Cummings, Ph. D. in the Department of Biochemistry and Molecular Biology at the University of Oklahoma Health Sciences Center. Following his defense, Dr. DeBose-Boyd joined the laboratory of Joseph L. Goldstein, M.D. and Michael S. Brown, M.D. at UT Southwestern Medical Center as a fellow of the Jane Coffin Childs Memorial Fund for Medical Research. After a successful postdoctoral fellowship, Drs. Goldstein and Brown invited Dr. DeBose-Boyd to join the faculty of the Molecular Genetics department as an Assistant Professor in 2003. He became an Established Investigator of the American Heart Association in 2005 and a W.M. Keck Distinguished Young Scholar in Medical Research in 2006. Dr. DeBose-Boyd was promoted to Associate Professor in 2007 and in 2009 he was appointed a Howard Hughes Medical Institute Early Career Scientist. In 2013, Dr. DeBose-Boyd was promoted to Professor and was named the Beatrice and Miguel Elias Distinguished Chair in Biomedical Science in 2016.


The Vitamin K2 Synthetic Enzyme UBIAD1 Moonlights as a Key Regulator of Cholesterol Synthesis

UbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4 (MK-4).  Mutations in UBIAD1 cause Schnyder corneal dystrophy (SCD), which is characterized by corneal opacification owing to over-accumulation of cholesterol.   Our studies disclosed a key role for UBIAD1 in regulating endoplasmic reticulum (ER)-localized HMG CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids including GGpp. Feedback control of reductase involves sterol-induced ubiquitination, an obligatory reaction for its ER-associated degradation (ERAD) that is augmented by GGpp.  Sterols also cause UBIAD1 to bind reductase, which inhibits ERAD and allows continued synthesis of nonsterol isoprenoids in sterol-replete cells.  GGpp triggers release of reductase from UBIAD1, enhancing ERAD and stimulating translocation of UBIAD1 to Golgi.  SCD-associated UBIAD1 resists GGpp-induced release from reductase and becomes sequestered in ER to inhibit ERAD.

     Gene knockout studies in mice were attempted to explore the in vivo function of UBIAD1; however, homozygous germ-line deletion of Ubiad1 caused embryonic lethality.  We generated homozygous deletion of Ubiad1 in knock-in mice expressing ubiquitination-resistant HMGCR, implying embryonic lethality results from enhanced ERAD of HMGCR. The study of Ubiad1-deficient mice offers the opportunity to determine the physiological significance of UBIAD1-mediated synthesis of MK-4.


Free and open to the university community and the public.


Nieng Yan, Department of Molecular Biology