holmes

Professor

Research Interests
oxalate handling and synthesis and its relationship to health and disease


Biography

Dr. 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.

Research Summary

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.

Education

Graduate
Australian National University, Ph.D.

Postdoctoral Training
University of Illinois at Champaign-Urbana

Institutional Activities

  • Graduate Biomedical Science Faculty (GBS)

      • Biochemistry and Structural Biology

      • Cell, Molecular & Developmental Biology

      • Pathobiology & Molecular Medicine

  • Appointment in Nephrology and Training Center

Society Memberships

  • Research on Calculus Kidney Kinetics (R.O.C.K) Society

  • American Society of Nephrology

  • American Society for Biochemistry and Molecular Biology

  • American Association for the Advancement of Science

Contact Information

Location
816 Kaul Genetics Building

Phone
205-996-2291