Pathobiology and Molecular Medicine  Back to Main

Faculty Detail    
Campus Address KAUL 816 Zip 0024
Phone  (205) 996-2295
Other websites

Graduate  University of Newcastle Upon Tyne    2001  PhD 

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

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

Biographical Sketch 
John Knight received his PhD in Physiology at the University of Newcastle-upon-Tyne in 2001. His initial postdoctoral studies, under the guidance of Mark Lively, PhD, in the Department of Otolaryngology, Wake Forest University Health Sciences, demonstrated that reflux of acid and pepsin from the stomach could play a role in voice disorders. In 2004, he joined the laboratory of Ross Holmes, PhD, Department of Urology, Wake Forest University Health Sciences, and shifted his research focus to oxalate handling associated with calcium oxalate kidney stone disease. His current efforts involve studies to better understand the biochemical pathways associated with endogenous oxalate synthesis and the role of oxalate degrading bacteria in oxalate homeostasis and calcium oxalate stone disease.

Society Memberships
Organization Name Position Held Org Link
American Physiological Society  Member   
Research On Calculus Kidney Kinetics (R.O.C.K) Society  Member   

Research/Clinical Interest
Oxalate Handling and Synthesis and its Relationship to Health and Disease
Increased levels of oxalic acid in plasma and urine can lead to a number of complications, including calcium oxalate kidney stone disease, calcium oxalate crystal deposition in tissues, cell death, and in the most extreme cases organ failure. Our research aims to better understand the biochemical pathways associated with oxalate synthesis, the factors that impact the absorption of dietary oxalate in our gastrointestinal tract, and the role of oxalate degrading bacteria in oxalate homeostasis. Model systems utilized include human studies in both patients and healthy volunteers, genetically modified mice, germ free mice, and cultured cells. The research utilizes carbon-13 stable isotopes and state-of-the-art ion chromatography equipment coupled to mass spectrometers to facilitate our understanding of oxalate handling and endogenous oxalate synthesis. Important achievements include the determination of factors that influence the colonization of the gastrointestinal tract with Oxalobacter formigenes, a clearer understanding of the contribution of dietary oxalate, dietary calcium, animal protein intake, fructose intake, glycine metabolism, phenylalanine metabolism, and hydroxyproline catabolism to urinary oxalate excretion, and clarifying the consequences of mutations in the rare diseases Primary Hyperoxaluria Type 2 and Type 3. Current and future research is focused on identifying metabolic pathways in the rare Primary Hyperoxaluria diseases that can be modulated to reduce oxalate synthesis, examining the ecology of Oxalobacter formigenes and under what circumstances it may reduce the risk of calcium oxalate kidney stone disease, and defining the factors that influence endogenous oxalate synthesis, including oxidative stress, mitochondrial dysfunction and Vitamin C intake.

Selected Publications 
Publication PUBMEDID
Johnston N, Knight J, Dettmar PW, Lively MO, Koufman J. Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease. Laryngoscope. 2004 Dec;114(12):2129-34.  PMID: 15564833 
Knight J, Holmes RP. Mitochondrial hydroxyproline metabolism: implications for primary hyperoxaluria. Am J Nephrol. 2005 Mar-Apr;25(2):171-5.   PMID: 15849464 
Knight J, Lively MO, Johnston N, Dettmar PW, Koufman JA. Sensitive pepsin immunoassay for detection of laryngopharyngeal reflux. Laryngoscope. 2005; Aug;115(8):1473-8.  PMID: 16094128 
Knight J, Holmes RP, Milliner DS, Monico CG, Cramer SD. Glyoxylate reductase activity in blood mononuclear cells and the diagnosis of primary hyperoxaluria type 2. Nephrol Dial Transplant. 2006 Aug;21(8):2292-5  PMID: 16597637  
Knight, J, Jiang J, Assimos DG, Holmes RP (2006). Hydroxyproline Ingestion and urinary oxalate and glycolate excretion. Kidney international 70 (11): 1929-34  PMID: 17021603 
Knight J, Holmes RP, Assimos DG. Intestinal and renal handling of oxalate loads in normal individuals and stone formers. Urol Res. 2007 Jun;35(3):111-7  PMID: 17431604  
Prokopovich S, Knight J, Assimos DG, Holmes RP. Variability of Oxalobacter formigenes and oxalate in stool samples.Urol. 2007 Nov;178(5):2186-90.   PMID: 17870112 
Knight J, Easter LH, Neiberg R, Assimos DG, Holmes RP (2009). Increased protein intake on controlled oxalate diets does not increase urinary oxalate excretion. Urological Research 37: 63-68.  PMID: 19183980 
Knight J, Assimos DG, Easter L, Holmes RP. Metabolism of fructose to oxalate and glycolate. Horm Metab Res. 2010 Nov;42(12):868-73.  PMID: 20842614 
Knight J, Assimos DG, Holmes RP, Callahan MF. (2010). Metabolism of Primed, Constant Infusions of [1,2-13C2] Glycine and [1-13C1] Phenylalanine to Urinary Oxalate. Metabolism: clinical and experimental. 60(7):950-6.  PMID: 21036374 
Maalouf NM, Adams Huet B, Pasch A, Lieske JC, Asplin JR, Siener R, Hesse A, Nuoffer JM, Frey FJ, Knight J, Holmes RP, Zerwekh JE, Bonny O. Variability in urinary oxalate measurements between six international laboratories. Nephrol Dial Transplant. 2011 Dec;26(12):3954-9.  PMID: 21454350 
Jiang J, Knight J, Easter LH, Neiberg R, Holmes RP, Assimos DG (2011). Impact of Dietary Calcium and Oxalate, and Oxalobacter Formigenes Colonization on Urinary Oxalate Excretion. Journal of Urology. 186(1):135-9.  PMID: 21575973  
Knight J, Jiang J, Wood KD, Holmes RP, Assimos DG. Oxalate and sucralose absorption in idiopathic calcium oxalate stone formers.Urology. 2011 Aug;78(2):475.  PMID: 21676449  
Riedel TJ, Johnson LC, Knight J, Hantgan RR, Holmes RP, Lowther WT. Structural and biochemical studies of human 4-hydroxy-2-oxoglutarate aldolase: implications for hydroxyproline metabolism in primary hyperoxaluria. PLoS One. 2011;6(10)  PMID: 21998747  
Knight J, Holmes RP, Cramer SD, Takayama T, Salido EC. Hydroxyproline metabolism in mouse models of primary hyperoxaluria. Am J Physiol Renal Physiol 2012 Mar 15;302(6):F688-93  PMID: 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. Am J Physiol Gastrointest Liver Physiol. 2012 Mar 15;302(6):G637-43  PMID: 22207577  
Lange JN, Wood KD, Mufarrij PW, Callahan MF, Easter L, Knight J, Holmes RP, Assimos DG. The impact of dietary calcium and oxalate ratios on stone risk. Urology 2012;79:1226-9.  PMID: 22480460 
Lange JN, Wood KD, Knight J, Assimos DG, Holmes RP. Glyoxal formation and its role in endogenous oxalate synthesis. Advances in Urology 2012: 2012: 19202  PMID: 22567004 
Lange JN, Wood KD, Wong H, Otto R, Mufarrij PW, Knight J, Akpinar H, Holmes RP, Assimos DG. Sensitivity of human strains of Oxalobacter formigenes to commonly prescribed antibiotics. Urology 2012;79: 1286-9.  PMID: 22656407 
Riedel TJ, Knight J, Murray MS, Milliner DS, Holmes RP, Lowther WT. 4-Hydroxy-2-oxoglutarate aldolase inactivity in primary hyperoxaluria type 3 and glyoxylate reductase inhibition. Biochim Biophys Acta. 2012 Oct;1822(10):1544-52.  PMID: 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(3):187-96.  PMID: 23632911  

Calcium oxalate kidney stone disease, Oxalobacter formigenes, primary hyperoxaluria