Biomedical Research Education & Training
Faculty Member

Christman, Brian W., M.D.
Professor of Medicine

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Phone Number: 615-322-3412

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Christman, Brian's picture
Academic history
B.S., Tulane
M.D., Oklahoma
, Vanderbilt
, Vanderbilt

Office Address   Mailing Address

T-1208 MCN, Vanderbilt/ Lab: B-1305-MCN

T-1218 MCN Division of Allergy, Pulmonary, and Critical Care Medicine 37232-2650

Research Keywords
Urea cycle; nitric oxide; nitric oxide synthase; peroxynitrite; isoprostanes; isofurans; sepsis; acute lung injury; oxidant stress; lipid peroxidation,Biochemistry,Enzyme action,Genetics,Mass spectroscopy,Mouse,Pharmacology,Polymorphism,Pulmonary

Clinical Research Keywords
Sepsis Acute Lung Injury ARDS Liver-lung interaction Urea Cycle Bone Marrow Transplant Pulmonary Hypertension

Patient Care Specialty
Pulmonary/Critical Care Medicine

Research Specialty
Role of urea/nitric oxide synthase cycle during inflammation

Research Description
Our research efforts are currently funded via two NIH grants: (1) PO1HL066196 (Program Project Grant-- Liver-lung interaction in the pathogenesis of lung inflammation, and (2) R01CA092313-- Chemotherapy Toxicity Reduction via Urea Cycle Support. By way of background, the hepatic urea cycle is the primary end pathway of nitrogen catabolism. This cycle fixes ammonia and generates urea. A key intermediate in the cycle is arginine, the substrate for NO generation via the actions of nitric oxide synthase. NOS, when provided with sufficient cofactors (NADPH, tetrahydrobiopterin, oxygen) and substrate, exists in a homodimeric form and produces mainly NO. During periods of substrate limitation or cofactor oxidation, "uncoupled NOS" generates large quantities of superoxide anion. In work supported by our PPG, we have found that mice with partial deficiency of proximal urea cycle enzymes experience increased post-endotoxin in vivo lipid peroxidation, as assessed by GC/MS measurement of isoprostanes and isofurans. This can be ameliorated by manipulation of NOS cofactors and substrate provision. In parallel studies supported by the NCI, we are engaged in a Phase II clinical trial of providing urea cycle intermediates to patients receiving escalated dose chemotherapy and stem cell transplant. This is aimed at reducing regimen related toxicity. . . . .

Clinical Research Description
We have found that escalated dose chemotherapy causes urea cycle dysfunction, decreased NO synthesis, and venocclusive disease in the liver. We are conducting a Phase II NIH sponsored clinical trial to determine if urea cycle support, by substrate provision, can limit tissue injury and in vivo oxidant stress after stem cell transplant.

Clinical Interests
Special interest in problems of lung disease associated with hepatic dysfunction, connective tissue disease-related lung dysfunction, bronchiolar diseases after HSCT, and pulmonary vascular disease. Also actively involved in care of patients with acute respiratory distress syndrome.

Robbins, IM, Hemnes, AR, Gibbs, JS, Christman, BW, Howard, L, Meehan, S, Cabrita, I, Gonzalez, R, Oyler, T, Zhao, L, Du, RH, Mendes, LA, Wilkins, MR. Safety of sapropterin dihydrochloride (6r-bh4) in patients with pulmonary hypertension. Exp Lung Res, 37(1), 26-34, 2011

Lee, HJ, Joo, M, Abdolrasulnia, R, Young, DG, Choi, I, Ware, LB, Blackwell, TS, Christman, BW. Peptidylarginine deiminase 2 suppresses inhibitory {kappa}B kinase activity in lipopolysaccharide-stimulated RAW 264.7 macrophages. J Biol Chem, 285(51), 39655-62, 2010

Robbins, IM, Kawut, SM, Yung, D, Reilly, MP, Lloyd, W, Cunningham, G, Loscalzo, J, Kimmel, SE, Christman, BW, Barst, RJ. A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension. Eur Respir J, 27(3), 578-84, 2006

Smith, HA, Canter, JA, Christian, KG, Drinkwater, DC, Scholl, FG, Christman, BW, Rice, GD, Barr, FE, Summar, ML. Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline. J Thorac Cardiovasc Surg, 132(1), 58-65, 2006

Kallianpur, AR, Hall, LD, Yadav, M, Byrne, DW, Speroff, T, Dittus, RS, Haines, JL, Christman, BW, Summar, ML. The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation. Bone Marrow Transplant, 35(12), 1155-64, 2005

Robbins, IM, Morrow, JD, Christman, BW. Oxidant stress but not thromboxane decreases with epoprostenol therapy. Free Radic Biol Med, 38(5), 568-74, 2005

Siore, AM, Parker, RE, Stecenko, AA, Cuppels, C, McKean, M, Christman, BW, Cruz-Gervis, R, Brigham, KL. Endotoxin-induced acute lung injury requires interaction with the liver. Am J Physiol Lung Cell Mol Physiol, 289(5), L769-76, 2005

Summar, ML, Barr, F, Dawling, S, Smith, W, Lee, B, Singh, RH, Rhead, WJ, Sniderman King, L, Christman, BW. Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin, 21(4 Suppl), S1-8, 2005

Wong, F, Bernardi, M, Balk, R, Christman, B, Moreau, R, Garcia-Tsao, G, Patch, D, Soriano, G, Hoefs, J, Navasa, M, , . Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. Gut, 54(5), 718-25, 2005 PMCID:1774473

Chen, Jian-xiong, Lawrence, Mayme Lee, Cunningham, Gary, Christman, Brian W, Meyrick, Barbara. HSP90 and Akt modulate Ang-1-induced angiogenesis via NO in coronary artery endothelium. J Appl Physiol, 96(2), 612-20, 2004

Humbert, M, Morrell, NW, Archer, SL, Stenmark, KR, MacLean, MR, Lang, IM, Christman, BW, Weir, EK, Eickelberg, O, Voelkel, NF, Rabinovitch, M. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol, 43(12 Suppl S), 13S-24S, 2004

Kallianpur, Asha R, Hall, Lynn D, Yadav, Meeta, Christman, Brian W, Dittus, Robert S, Haines, Jonathan L, Parl, Fritz F, Summar, Marshall L. Increased prevalence of the HFE C282Y hemochromatosis allele in women with breast cancer. Cancer Epidemiol Biomarkers Prev, 13(2), 205-12, 2004

Richard, C, Gao, J, LaFleur, B, Christman, BW, Anderson, J, Brown, N, Reese, J. Patency of the preterm fetal ductus arteriosus is regulated by endothelial nitric oxide synthase and is independent of vasa vasorum in the mouse. Am J Physiol Regul Integr Comp Physiol, 287(3), R652-60, 2004

Summar, ML, Hall, L, Christman, B, Barr, F, Smith, H, Kallianpur, A, Brown, N, Yadav, M, Willis, A, Eeds, A, Cermak, E, Summar, S, Wilson, A, Arvin, M, Putnam, A, Wills, M, Cunningham, G. Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I. Mol Genet Metab, 81 Suppl 1, S12-9, 2004

Summar, Marshall L, Gainer, James V, Pretorius, Mias, Malave, Hector, Harris, Stephanie, Hall, Lynn D, Weisberg, Alec, Vaughan, Douglas E, Christman, Brian W, Brown, Nancy J. Relationship between carbamoyl-phosphate synthetase genotype and systemic vascular function. Hypertension, 43(2), 186-91, 2004

Barr, FE, Beverley, H, VanHook, K, Cermak, E, Christian, K, Drinkwater, D, Dyer, K, Raggio, NT, Moore, JH, Christman, B, Summar, M. Effect of cardiopulmonary bypass on urea cycle intermediates and nitric oxide levels after congenital heart surgery. J Pediatr, 142(1), 26-30, 2003

Chen, Daohong, Balyakina, Elena V, Lawrence, Mayme, Christman, Brian W, Meyrick, Barbara. Cyclooxygenase is regulated by ET-1 and MAPKs in peripheral lung microvascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol, 284(4), L614-21, 2003

Chen, Jian-Xiong, Berry, Leonard C, Christman, Brian W, Meyrick, Barbara. Glutathione mediates LPS-stimulated COX-2 expression via early transient p42/44 MAPK activation. J Cell Physiol, 197(1), 86-93, 2003

Langleben, David, Christman, Brian W, Barst, Robyn J, Dias, Virgil C, Gali??, Nazzareno, Higenbottam, Timothy W, Kneussl, Meinhard, Korducki, Larry, Naeije, Robert, Riedel, Axel, Simonneau, Gerald, Hirsch, Andrew M, Rich, Stuart, Robbins, Ivan M, Oudiz, Ronald, McGoon, Michael D, Badesch, David B, Levy, Robert D, Mehta, Sanjay, Seeger, Werner, Sol??r, Markus. Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension. Am Heart J, 143(5), E4, 2002

Blackwell, T S, Christman, J W, Hagan, T, Price, P, Edens, T, Morris, P E, Wolff, S N, Goodman, S A, Christman, B W. Oxidative stress and NF-kappaB activation: correlation in patients following allogeneic bone marrow transplantation. Antioxid Redox Signal, 2(1), 93-102, 2001

Chen, J X, Berry, L C, Christman, B W, Tanner, M, Myers, P R, Meyrick, B O. NO regulates LPS-stimulated cyclooxygenase gene expression and activity in pulmonary artery endothelium. Am J Physiol Lung Cell Mol Physiol, 280(3), L450-7, 2001

Collins, B J, Blum, M G, Parker, R E, Chang, A C, Blair, K S, Zorn, G L, Christman, B W, Pierson, R N. Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection. J Appl Physiol, 90(6), 2257-68, 2001

Dworski, R, Christman, BW, Sheller, JR. Quantitative analysis of f(2) isoprostanes. Methods Mol Med, 56, 423-30, 2001

Dworski, R, Sheller, JR, Christman, BW. Quantitative analysis of cyclooxygenase metabolites of arachidonic Acid. Methods Mol Med, 56, 411-22, 2001

Klings, E S, Christman, B W, McClung, J, Stucchi, A F, McMahon, L, Brauer, M, Farber, H W. Increased F2 isoprostanes in the acute chest syndrome of sickle cell disease as a marker of oxidative stress. Am J Respir Crit Care Med, 164(7), 1248-52, 2001

Pearson, D L, Dawling, S, Walsh, W F, Haines, J L, Christman, B W, Bazyk, A, Scott, N, Summar, M L. Neonatal pulmonary hypertension--urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med, 344(24), 1832-8, 2001

Robbins, I M, Barst, R J, Rubin, L J, Gaine, S P, Price, P V, Morrow, J D, Christman, B W. Increased levels of prostaglandin D(2) suggest macrophage activation in patients with primary pulmonary hypertension. Chest, 120(5), 1639-44, 2001

Haselton, D J, Klekamp, J G, Christman, B W, Barr, F E. Use of high-dose corticosteroids and high-frequency oscillatory ventilation for treatment of a child with diffuse alveolar hemorrhage after bone marrow transplantation: case report and review of the literature. Crit Care Med, 28(1), 245-8, 2000

Mangialardi, R J, Martin, G S, Bernard, G R, Wheeler, A P, Christman, B W, Dupont, W D, Higgins, S B, Swindell, B B. Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis. Ibuprofen in Sepsis Study Group. Crit Care Med, 28(9), 3137-45, 2000

Arons, M M, Wheeler, A P, Bernard, G R, Christman, B W, Russell, J A, Schein, R, Summer, W R, Steinberg, K P, Fulkerson, W, Wright, P, Dupont, W D, Swindell, B B. Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group. Crit Care Med, 27(4), 699-707, 1999

Costa, F, Sulur, P, Angel, M, Cavalcante, J, Haile, V, Christman, B, Biaggioni, I. Intravascular source of adenosine during forearm ischemia in humans: implications for reactive hyperemia. Hypertension, 33(6), 1453-7, 1999

Martin, G S, Christman, B W, Standaert, S M. Rapidly fatal infection with Ehrlichia chaffeensis. N Engl J Med, 341(10), 763-4, 1999

Alexander, J S, Patton, W F, Christman, B W, Cuiper, L L, Haselton, F R. Platelet-derived lysophosphatidic acid decreases endothelial permeability in vitro. Am J Physiol, 274(1 Pt 2), H115-22, 1998

Becker, P M, Sanders, S P, Price, P, Christman, B W. F2-isoprostane generation in isolated ferret lungs after oxidant injury or ventilated ischemia. Free Radic Biol Med, 25(6), 703-11, 1998

Carpenter, C T, Price, P V, Christman, B W. Exhaled breath condensate isoprostanes are elevated in patients with acute lung injury or ARDS. Chest, 114(6), 1653-9, 1998

Christman, B W. Lipid mediator dysregulation in primary pulmonary hypertension. Chest, 114(3 Suppl), 205S-207S, 1998

Robbins, I M, Christman, B W, Newman, J H, Matlock, R, Loyd, J E. A survey of diagnostic practices and the use of epoprostenol in patients with primary pulmonary hypertension. Chest, 114(5), 1269-75, 1998

Robbins, I M, Cuiper, L L, Stein, C M, Wood, A J, He, H B, Parker, R, Christman, B W. Angiotensin II mediates systemic rebound hypertension after cessation of prostacyclin infusion in sheep. J Appl Physiol, 85(2), 731-7, 1998

Tchekneva, E, Quertermous, T, Christman, B W, Lawrence, M L, Meyrick, B. Regional variability in preproEndothelin-1 gene expression in sheep pulmonary artery and lung during the onset of air-induced chronic pulmonary hypertension. Participation Of arterial smooth muscle cells. J Clin Invest, 101(6), 1389-97, 1998 PMCID:508694

Bernard, G R, Wheeler, A P, Russell, J A, Schein, R, Summer, W R, Steinberg, K P, Fulkerson, W J, Wright, P E, Christman, B W, Dupont, W D, Higgins, S B, Swindell, B B. The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med, 336(13), 912-8, 1997

He, H, Stein, CM, Christman, B, Wood, AJ. Determination of catecholamines in sheep plasma by high-performance liquid chromatography with electrochemical detection: comparison of deoxyepinephrine and 3,4-dihydroxybenzylamine as internal standard. J Chromatogr B Biomed Sci Appl, 701(1), 115-9, 1997

Blackwell, T S, Blackwell, T R, Holden, E P, Christman, B W, Christman, J W. In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation. J Immunol, 157(4), 1630-7, 1996

Cuiper, L L, Price, P V, Christman, B W. Systemic and pulmonary hypertension after abrupt cessation of prostacyclin: role of thromboxane A2. J Appl Physiol, 80(1), 191-7, 1996

Meyrick, B, Berry, L C, Christman, B W. Response of cultured human pulmonary artery endothelial cells to endotoxin. Am J Physiol, 268(2 Pt 1), L239-44, 1995

Biggs, V J, Dummer, S, Holsinger, F C, Loyd, J E, Christman, B W, Frist, W H. Successful treatment of invasive bronchial aspergillosis after single-lung transplantation. Clin Infect Dis, 18(1), 123-4, 1994

Conary, J T, Parker, R E, Christman, B W, Faulks, R D, King, G A, Meyrick, B O, Brigham, K L. Protection of rabbit lungs from endotoxin injury by in vivo hyperexpression of the prostaglandin G/H synthase gene. J Clin Invest, 93(4), 1834-40, 1994 PMCID:294257

Brigham, KL, Meyrick, B, Christman, B, Conary, JT, King, G, Berry, LC, Magnuson, MA. Expression of human growth hormone fusion genes in cultured lung endothelial cells and in the lungs of mice. Am J Respir Cell Mol Biol, 8(2), 209-13, 1993

Christman, B W, Bernard, G R. Antilipid mediator and antioxidant therapy in adult respiratory distress syndrome. New Horiz, 1(4), 623-30, 1993

Christman, B W, Christman, J W, Dworski, R, Blair, I A, Prakash, C. Prostaglandin E2 limits arachidonic acid availability and inhibits leukotriene B4 synthesis in rat alveolar macrophages by a nonphospholipase A2 mechanism. J Immunol, 151(4), 2096-104, 1993

Kuratomi, Y, Lefferts, P L, Christman, B W, Parker, R E, Smith, W G, Mueller, R A, Snapper, J R. Effect of a 5-lipoxygenase inhibitor on endotoxin-induced pulmonary dysfunction in awake sheep. J Appl Physiol, 74(2), 596-605, 1993

Christman, B W, McPherson, C D, Newman, J H, King, G A, Bernard, G R, Groves, B M, Loyd, J E. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med, 327(2), 70-5, 1992

Trochtenberg, D S, Lefferts, P L, King, G A, Hwang, Y S, Christman, B W, Snapper, J R. Effects of thromboxane synthase and cyclooxygenase inhibition on PAF-induced changes in lung function and arachidonic acid metabolism. Prostaglandins, 44(6), 555-77, 1992

Christman, B W, Gay, J C, Christman, J W, Prakash, C, Blair, I A. Analysis of effector cell-derived lyso platelet activating factor by electron capture negative ion mass spectrometry. Biol Mass Spectrom, 20(9), 545-52, 1991

Christman, J W, Christman, B W, Shepherd, V L, Rinaldo, J E. Regulation of alveolar macrophage production of chemoattractants by leukotriene B4 and prostaglandin E2. Am J Respir Cell Mol Biol, 5(3), 297-304, 1991

Meyrick, B, Christman, B, Jesmok, G. Effects of recombinant tumor necrosis factor-alpha on cultured pulmonary artery and lung microvascular endothelial monolayers. Am J Pathol, 138(1), 93-101, 1991 PMCID:1886052

Christman, B W, Lefferts, P L, Blair, I A, Snapper, J R. Effect of platelet-activating factor receptor antagonism on endotoxin-induced lung dysfunction in awake sheep. Am Rev Respir Dis, 142(6 Pt 1), 1272-8, 1990

Schapira, M, Christman, B W. Neutralization of heparin by protamine. Time for a change?. Circulation, 82(5), 1877-9, 1990

Takahashi, K, Schreiner, G F, Yamashita, K, Christman, B W, Blair, I, Badr, K F. Predominant functional roles for thromboxane A2 and prostaglandin E2 during late nephrotoxic serum glomerulonephritis in the rat. J Clin Invest, 85(6), 1974-82, 1990 PMCID:296666

Brigham, KL, Meyrick, B, Christman, B, Berry, LC, King, G. Expression of a prokaryotic gene in cultured lung endothelial cells after lipofection with a plasmid vector. Am J Respir Cell Mol Biol, 1(2), 95-100, 1989

Brigham, KL, Meyrick, B, Christman, B, Magnuson, M, King, G, Berry, LC. In vivo transfection of murine lungs with a functioning prokaryotic gene using a liposome vehicle. Am J Med Sci, 298(4), 278-81, 1989

Christman, B W, Blair, I A. Analysis of platelet activating factor in human saliva by gas chromatography/mass spectrometry. Biomed Environ Mass Spectrom, 18(4), 258-64, 1989

Christman, B W, Lefferts, P L, King, G A, Snapper, J R. Role of circulating platelets and granulocytes in PAF-induced pulmonary dysfunction in awake sheep. J Appl Physiol, 64(5), 2033-41, 1988

Coggeshall, J W, Christman, B W, Lefferts, P L, Serafin, W E, Blair, I A, Butterfield, M J, Snapper, J R. Effect of inhibition of 5-lipoxygenase metabolism of arachidonic acid on response to endotoxemia in sheep. J Appl Physiol, 65(3), 1351-9, 1988

Christman, B W, Lefferts, P L, Snapper, J R. Effect of platelet-activating factor on aerosol histamine responsiveness in awake sheep. Am Rev Respir Dis, 135(6), 1267-70, 1987

Snapper, J R, Coggeshall, J W, Serafin, W E, Phillips, M A, Lefferts, P L, Christman, B W. Role of leukotrienes in an animal model of the adult respiratory distress syndrome. Adv Prostaglandin Thromboxane Leukot Res, 17B, 1043-6, 1987

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