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Faculty Detail    
Name ROSS P. HOLMES
 
Campus Address KAUL 816 Zip 0024
Phone  (20-5) -291
E-mail  rholmes@uab.edu
Other websites
     

Education
Graduate  Australian National University    1978  PhD 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Urology   Urology Chair Office Professor
Center  General Clinical Research Center  Nephrology Research & Training Center Professor
Center  Nutrition Sciences   Nutrition Obesity Res Ctr (NORC) Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Ross Holmes studied calcium handling in a slime mold that was a multinucleated giant cell for his PhD studies in Biochemistry at the Australian National University, graduating in 1978. On moving to the University of Illinois at Champaign-Urbana he investigated the role of calcium and membrane perturbations in heart disease. Subsequently on joining the faculty at Wake Forest University in 1987 his focus shifted to examining calcium and oxalate handling associated with calcium oxalate stone disease. Major achievements while there were in establishing the role of dietary oxalate in stone disease, cloning the gene causing the rare disease, Primary Hyperoxaluria Type 2, identifying mutations in patients, and in clarifying the biochemical pathways associated with hepatic oxalate synthesis.

Society Memberships
Organization Name Position Held Org Link
American Society for Biochemistry and Molecular Biology     
American Society for Nutrition     



Research/Clinical Interest
Title
Oxalate Handling and Synthesis and its Relationship to Health and Disease
Description
Our current research focuses on biochemical pathways associated with oxalate synthesis. Aspects under investigation include the clarification of the steps involved, determining how the pathways are regulated and how they can be modulated, and identifying perturbations that cause disease. Pathways under consideration are the metabolism of hydroxyproline, the metabolism of the peroxidation product, glyoxal, and the breakdown of vitamin C. A particular disease-causing perturbation under investigation is a futile glycolate cycle that is associated with Primary Hyperoxaluria Type 1 and generates hydrogen peroxide. We propose that this impairs mitochondrial function. Model systems are used in these investigations and include human studies, the use of genetically modified mice and cell culture. Important techniques used are HPLC, ion chromatography coupled to mass detection, Western blotting, and confocal microscopy. Monitoring the metabolism of isotopically-labeled oxalate precursors infused in humans and mice will continue to be an important research tool.

Selected Publications 
Publication PUBMEDID
Murray MS, Holmes RP, Lowther WL. Active site and loop 4 movements within human glycolate oxidase: Implications for substrate specificity and drug design. Biochemistry 2008; 47: 2439-2449.   18215067 
Knight J, Easter LH, Neiberg R, Assimos DG, Holmes RP. Increased protein intake on controlled oxalate diets does not increase urinary oxalate excretion. Urol Res 2009; 37: 63-68.   19183980 
Knight J, Assimos DG, Easter L, Holmes RP. Metabolism of fructose to oxalate and glycolate. Hormone and Metabolic Research 2010; 42: 868-873.  20842614 
Knight J, Assimos DG, Callahan MF, Holmes RP. Metabolism of primed, constant infusions of [1,2-13C2] glycine and [1-13C1] phenylalanine to urinary oxalate. Metabolism 2011; 60: 950-956.  21036374 
Jiang J, Knight J, Easter LH, Neiberg R, Holmes RP, Assimos DG. Impact of dietary oxalate and Oxalobacter formigenes on urinary oxalate excretion. J Urol 2011; 186: 135-139.  21575973 
Riedel TJ, Johnson LC, Knight J, Hantgan RR, Holmes RP, Lowther WT. Crystallographic and biochemical studies of human 4-hydroxy-2-oxoglutarate aldolase: implications for hydroxyproline metabolism in primary hyperoxaluria. PlosOne 2011; 6:e26021.  21998747 
Knight J, Hinsdale M, Holmes RP. The glycolate and 2-phosphoglycolate content of tissues measured by ion chromatography coupled with mass spectrometry. Anal Biochem 2012; 421: 121-124.  22093610 
Knight J, Holmes RP, Cramer SD, Takayama T, Salido EC. Hydroxyproline metabolism in mouse models of primary hyperoxaluria. Amer J Physiol Renal Physiol 2012; 302: F688-F693.  22189945 
Jiang J, Johnson LC, Knight J, Callahan MF, Holmes RP, Lowther WT. Metabolism of 13C5-hydroxyproline metabolism in vitro and in vivo: implications for primary hyperoxaluria. Amer J Physiol Gastro Intest Liver Physiol 2012; 302: G637-G643.  22207577 
Lange JN, Wood KD, Knight J, Assimos DG, Holmes RP. Glyoxal formation and its role in endogenous oxalate synthesis. Advances in Urology 2012; 819202.  22480460 
Riedel TJ, Knight J, Murray MS, Milliner DS, Holmes RP, Lowther WT. 4-Hydroxy-2-oxoglutarate adolase inactivity in Primary Hyperoxaluria Type 3 and glyoxylate reductase inhibition. BBA Molecular Basis of Disease 2012; 1822: 1544-1552.  22771891 
Knight J, Deora R, Assimos DG, Holmes RP. The genetic composition of Oxalobacter formigenes and its relationship to colonization and calcium oxalate stone disease. Urolithiasis 2013; 41:187-196  23632911 

Keywords
urolithiasis, oxalate, glycolate, hydroxyproline, metabolism