Juan C. Marini, D.V.M., Ph.D.
Assistant Professor of Pediatrics
Dr. Marini’s research is focused on urea cycle intermediates and their role in supporting ureagenesis and nitric oxide production. Current studies are aimed at increasing our understanding of how the supply of urea cycle intermediates help overcome reduced enzymatic activity found in urea cycle disorder models. We are also investigating the role of genetic background and interorgan transactions of urea cycle intermediates in ornithine transcarbamylase deficiency murine models. In this hypomorphic model, we have shown that the exogenous supply of ornithine is able to restore ureagenesis and mitigate hyperammonemia in C57 mice. However, due to an increase in endogenous ornithine production, mice of different genetic backgrounds harboring the same mutation do not become hyperammonemic.
We are also investigating the role of arginine and intracellular citrulline recycling in sustaining nitric oxide production during basal conditions and LPS challenge in different mouse models. The combination of mouse genetic models and the determination of metabolite fluxes utilizing minimally invasive techniques offers the possibility to study complex pathways and interorgan transaction at the whole organism level in conscious animals.
Benight, N., B. Stoll, J.C. Marini and D.G. Burrin. 2012. Preventive oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice. Am J Physiol 303:G71-G82.
Nagamani, S.C.S., P.M. Campeau, O.A. Schelochkov, M.H. Premkumar, K. Guse, N. Brunetti-Pierri, Y. Chen, Q. Sun, Y. Tang, D. Palmer, A.K. Reddy, L. Li, T.C. Slesnick, D.I. Feig, S. Caudle, D. Harrison, L. Salviati, J.C. Marini, N.S. Bryan, A. Erez, and B. Lee. 2012. Nitric-oxide supplementation for treatment of long term complications in argininosuccinic aciduria. Am J Hum Genet 90:836-846
Chacko, S., M.W Haymond, Y. Sun, J.C. Marini, P.J.J. Sauer, X. Ma, and A.L. Sunehag. 2012. Effect of ghrelin on glucose regulation in mice. Am J Physiol 302:E1055-E1062.
Marini, J.C. 2012. Arginine and ornithine are the main precursors for citrulline synthesis in mice. J Nutr 142:572-580.
Erez A., S.C.S. Nagamani, O.A. Shchelochkov, M.H. Premkumar, P.M. Campeau, Y. Chen, H.K. Garg, L. Li, A. Mian, T.K. Bertin, J.O. Black, H. Zeng, Y. Tang, A.K. Reddy, M. Summar, W.E. O'Brien, D.G. Harrison, W.E. Mitch, J.C. Marini, J.L. Aschner, N.S. Bryan and B. Lee. 2011. Requirement of argininosuccinate lyase for systemic nitric oxide production. Nature Med. 17: 1619-1626.
Benight, N., B. Stoll, S. Chacko, V.R. da Silva, J.C. Marini, J.F. Gregory, S. P. Stabler, and D.G. Burrin. 2011. B-vitamin Deficiency is Protective Against DSS-Induced Colitis in Mice. Am J Physiol 301:G249-259.
Marini, J.C., B.C. Lanpher, F. Scaglia, W.E. O’Brien, Q. Sun, P.J. Garlick, F. Jahoor, and B. Lee. 2011. Phenylbutyrate improves nitrogen disposal via an alternative pathway without eliciting an increase in protein breakdown and catabolism in control and ornithine transcarbamylase-deficient patients. Am J Clin Nutr 93:1248-1254.
Marini, J.C. 2011. Quantitative analysis of (15)N-labeled positional isomers of glutamine and citrulline via electrospray ionization tandem mass spectrometry of their dansyl derivatives. Rapid Commun Mass Spectrom 25:1291-1296
Brunetti-pierri, N., B. Lanpher, A. Erez, E.A. Ananieva, M. Islam, J.C. Marini, Q. Sun, C. Yu, M. Hegde, J. Li, R.M. Wynn, D.T. Chuang, S. Hutson, and B. Lee. 2011. Phenylbutyrate therapy for maple syrup urine disease. Human Molec Gen 20: 631-640.
Thame, M.M., H.M. Fletcher, T.M. Baker, J.C. Marini, C. C. Kao, and F. Jahoor. 2011. Arginine flux, but not nitric oxide synthesis, decreases in adolescent girls compared with adult women during pregnancy. J Nutr 141: 71-74.
Marini, J.C., I.C. Didelija, L. Castillo and B. Lee. 2011. Enteral arginase II provides ornithine for citrulline synthesis. Am J Physiol 300:E188-E194.
Marini, J.C., I.C. Didelija, L. Castillo and B. Lee. 2010. Plasma arginine and ornithine are the main citrulline precursors in mice infused with arginine-free diets. J Nutr 140:1432-1437.
Marini, J.C., I.C. Didelija, L. Castillo and B. Lee. 2010. Glutamine: precursor or nitrogen donor for the synthesis of citrulline. Am J Physiol 299:E69-E79.
Nichols, B.L., Quezada-Caillo R., Robayo-Torres C.C., AO, Z.H., Hamaker, B.R., Butte, N.F., Marini. J.C., Jahoor, F., Sterchi, E.E. 2009. Mucosal maltas-glucoamylase plays a crucial role in starch digestion and prandial glucose homeostasis of mice. J Nutr 139:684-690.
Marini, J.C., D.G. Fox, and M.R. Murphy. 2008. Nitrogen transactions along the gastrointestinal tract of cattle: A meta-analytical approach. J Anim Sci 86:660-679.
Marini, J.C., A. Erez, L. Castillo, B. Lee. 2007. The interaction between murine spf-ash mutation and genetic background yield different metabolic genotypes. Am J Physiol 293:E1764-E1771.
Chowdhury, S.R., D.E. King, B.P. Willing, M.R. Band, J.E. Beever, A.B. lane, J.J. Loor, J.C. Marini, L.A. Rund, L.B. Schook, A.G. Van Kessel, H.R. Gaskins. 2007. Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets. BMC Genomics 8:215.
Marini, J.C., M.S. Attene-Ramos. 2006. An improved analytical method for the determination of urea nitrogen isotopomers in biological samples utilizing continuous flow-isotope ratio mass spectrometry. Rapid Commun Mass Spectrom 20:3736-3740.
Marini, J.C., B. Lee, P.J. Garlick. 2006. Non-surgical alternatives to surgical procedures in mice. Lab. Animals 40:275-281.
Marini, J.C., B. Lee, P.J. Garlick. 2006. Ornithine restores ureagenesis capacity and mitigates hyperammonemia in Otcspf-ash mice. J Nutr 136:1834-1838.
Imoberdorf, R., P.J. Garlick, M.A. McNurlan, G.A. Casella, J.C. Marini, M Turgay, P Barstsch, P.E. Ballmer. 2006. The effect of acute active or passive ascent to high altitude on human skeletal muscle protein synthesis. Med Sci Sports Exerc 38:1082-1087.
Marini, J.C., S. Broussard. 2006. Hyperammonemia increases sensitivity to LPS. Mol Genet Metab 88:131-37.
Marini, J.C., B. Lee, P.J. Garlick. 2006. Reduced ornithine transcarbamylase activity does not impair ureagenesis in Otcspf-ash mice. J Nutr 136:1017-1020.
Marini, J.C., B. Lee, P.J. Garlick. 2006. In vivo urea kinetic studies in conscious mice. J Nutr 136:202-206.
Marini, J.C. and M. E. Van Amburgh. 2005. Partition of nitrogen excretion in the urine and the feces of Holstein replacement heifers. J Dairy Sci 88:1778-1784..
Marini, J.C., J.D. Klein, J.M. Sands and M.E. Van Amburgh. 2004. Effect of N intake on N recycling and urea transporter expression in lambs. J Anim Sci 82:1157-1164.
Scaglia, F., N. Brunetti-Pierri, S. Kleppe, J. Marini, S. Carter, P. Garlick, F. Jahoor, W. O’Brien, and B. Lee. 2003. Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism. J Nutr. 134:2775S-2782S.
Scaglia, F., J. Marini, J. Rosenberger, J. Henry, P. Garlick, and P. Reeds. 2003. Differential utilization of systemic and enteral ammonia for urea synthesis in control subjects and carriers for ornithine transcarbamylase deficiency. Am J Clin Nutr 78:749-755.
Marini, J.C., K.W. Simpson , A. Gerold , M.E. Van Amburgh. 2003. The effect of immunization with jackbean urease on antibody response and nitrogen recycling in mature sheep. Livest Prod Sci 81:283-292.
Marini, J.C. and M.E. Van Amburgh. 2003. Nitrogen metabolism and recycling in Holstein heifers. J Anim Sci 81:545-552.
Ruiz, R., L.O. Tedeschi, J.C. Marini, D.G. Fox, A.N. Pell, G. Jarvis, and J.B Russell. 2002. The effect of a ruminal nitrogen (N) deficiency in dairy cows: evaluation of the Cornell Net Carbohydrate and Protein System ruminal N deficiency adjustment. J Dairy Sci 85:2986-2999.
Marini, J. C. 2010. Citrulline and urea metabolism in the gut. In: G. M. Crovetto, editor. Energy and protein metabolism and nutrition: 3rd International Symposium on Energy and Protein Metabolism and Nutrition; 2010, Parma, Italy. Wageningen Academic Publishers.
Scaglia, F., B. Lanpher, J.C. Marini, and B. Lee. 2007. Role of branched chain amino acids in patients with urea cycle disorders. In Pathophysiology and Management of Hyperammonaemia. Edited by C. Bachmann, J Haberle, and J. Leonard. SPS Verlagsgesellschaft, Heilbronn, Germany.
Marini, J.C., J. Sands and M. E. Van Amburgh. 2005. Urea transport systems in relation to recycling. In Ruminant physiology: Digestion, metabolism and impact of nutrition on gene expression, immunology and stress. Edited by K. Sejrsen, T. Hvelplund and M.O. Nielsen. Wageningen Academic Publishers, Wageningen, The Netherlands.