²ÝÁñÉçÇøÈë¿Ú

Positions

Associate Professor

²ÝÁñÉçÇøÈë¿Ú

Addresses

Alkek Building for Biomedical Research (Lab)

ABBR-R807
MS: BCM225
Houston, TX 77030
United States
Phone: (713) 798-7554
burrage@bcm.edu

Education

M.D, Ph.D. from Case Western Reserve University

05/2008 - Cleveland, Ohio United States

Residency at Case Medical Center University Hospital

Cleveland, Ohio United States

Pediatrics

Residency at ²ÝÁñÉçÇøÈë¿Ú

Houston, Texas United States

Medical Genetics

Fellowship at ²ÝÁñÉçÇøÈë¿Ú

Houston, Texas United States

Biochemical Genetics

Certifications

General Pediatrics

American Board of Pediatrics

Clinical Genetics

American Board of Medical Genetics and Genomics

Biochemical Genetics

American Board of Medical Genetics and Genomics

Professional Statement

As a physician-scientist and clinical biochemical geneticist, I have a long-standing interest in the pathophysiology of inborn errors of metabolism and their utility as models for more common disorders. Our group uses laboratory-based approaches in murine models and clinical studies to gain greater understanding of the etiology of long-term complications of inborn errors of metabolism with a special focus on urea cycle disorders in order to optimize management strategies for our patients.
One main focus of my research program is to gain a greater understanding of chronic liver dysfunction in individuals with urea cycle disorders. As an investigator in the Urea Cycle Disorders Consortium (UCDC) of the Rare Diseases Clinical Research Network, I have pursued a variety of data-mining projects using data from the UCDC Longitudinal Study of Urea Cycle Disorders. Using this data, we discovered an increased prevalence of chronic hepatocellular injury in two distal urea cycle disorders (argininosuccinate lyase deficiency and arginase deficiency) compared to disorders impacting enzymes that are more proximal in the cycle. To follow-up this work, we are performing a more comprehensive assessment of liver disease using serum biomarkers and novel imaging techniques in individuals with urea cycle disorders.
Our clinical study of hepatic complications complements our laboratory-based work in the murine models of urea cycle disorders. First, we are investigating the underlying mechanisms for liver disease in mouse models of argininosuccinate lyase (ASL) deficiency. The ASL-deficient mice model the human disorder with urea cycle dysfunction, nitric oxide (NO) deficiency, and chronic hepatocellular injury with hepatomegaly. In addition, as in human patients with the disorder, we have recently discovered hepatic glycogen accumulation and impaired hepatic glycogenolysis in these mice. Second, we are utilizing in vitro and in vivo models to investigate the underlying mechanisms of Lysinuric Protein Intolerance, a secondary urea cycle disorder, that is associated with osteoporosis, failure to thrive, and immune dysregulation.
To complement my independent research program, I am also involved in a variety of large interdisciplinary research teams focusing on various aspects of rare disease research. As an investigator in the Urea Cycle Disorders Consortium, I am involved in a wide variety of multi-center clinical research initiatives focused on urea cycle disorders. Locally, at Baylor, I have a leadership role in the sequence analysis team (e.g. exome and whole genome) for the ²ÝÁñÉçÇøÈë¿Ú site for the Undiagnosed Diseases Network (UDN). The work of our team has led to discovery of multiple potential new disease genes and phenotypic expansion in the setting of a wide variety of phenotypes. In addition, I am one of the principal investigators for the new Baylor Center for Precision Medicine Models. This large collaborative project focuses on the generation and use of precision medicine models to support gene discovery in rare undiagnosed diseases and to facilitate pre-clinical studies to investigate therapies for these disorders.

Websites

Selected Publications

• Brooks D, Burke E, Lee S, Eble TN, O'Leary M, (…); Undiagnosed Diseases Network; Lalani S, Rosenfeld JA, Burrage LC "." Hum Genet. 2024;143:279-291. Pubmed PMID:
• Stroup BM, Li X, Ho S, Zhouyao H, Chen Y, Ani S, Dawson B, Jin Z, Marom R, Jiang MM, Lorenzo I, Rosen D, Lanza D, Aceves N, Koh S, Seavitt JR, Heaney JD, Lee B, Burrage LC "." Dis Model Mech.. 2023;16:dmm050118. Pubmed PMID:
• Santiago-Sim T*, Burrage LC* et al. "." Am. J. Hum. Genet. 2017 Apr;100(4):676-688. Pubmed PMID:
• Burrage LC et al. "." Hum. Mol. Genet. 2015 Nov 15;24(22):641-27. Pubmed PMID:

Funding

Impaired Glycogen Metabolism and Chronic Liver Disease in Urea Cycle Disorders

Burroughs Wellcome Fund Career Award for Medical Scientists

Dissecting the Link Between Ureagenesis and Hepatic Glycogen Metabolism

NIH R01DK126786