Fred S. Lamb, M.D., Ph.D.

Professor

fred.s.lamb@vanderbilt.edu
Faculty Appointments
Professor of Pediatrics Professor of Molecular Physiology and BiophysicsCornelius Vanderbilt Chair
Education
Ph.D., University of Michigan, Ann Arbor, MichiganM.D., MEDICINE, University of Michigan, Ann Arbor, MichiganB.S., University of Michigan, Ann Arbor, Michigan
Research Description
Inflammatory cytokines are critical drivers of inflammation and important therapeutic targets in inflammatory diseases such as arthritis and colitis. They also underly the inflammatory response that is associated with hypertension and atherosclerosis. We have identified two anion transporters, the ClC-3 Cl-/H+ exchanger and LRRC8 family anion channels, which are required for superoxide production by the Nox1 NADPH oxidase. Reactive oxygen produced by Nox1 is in-turn essential for signaling by TNFalpha, IL-1beta and for endotoxin signaling through TLR4 receptors. The long-term goal of my laboratory is to determine if these proteins can be pharmacologically targeted to modulate cytokine signaling and control inflammation. Our primary research focus is to define the functional relationship between these proteins and Nox1, and to explore the impact of anion transport inhibition on superoxide production and inflammation in both cultured cell and whole animal models.
Clinical Description
I am the Division Head for Pediatric Critical Care, and practice as an attending physician in the Pediatric Cardiac ICU.
Research Keywords
Inflammation, Cytokine Signaling, TNFalpha, Hypertension, Atherosclerosis, ClC-3, LRRC8, Nox1,
Publications
Choi H, Ettinger N, Rohrbough J, Dikalova A, Nguyen HN, Lamb FS. LRRC8A channels support TNFa-induced superoxide production by Nox1 which is required for receptor endocytosis. Free Radic. Biol. Med [print-electronic]. 2016 Nov 11/9/2016; 101: 413-23. PMID: 27838438, PII: S0891-5849(16)31028-0, DOI: 10.1016/j.freeradbiomed.2016.11.003, ISSN: 1873-4596.

Kraemer MP, Choi H, Reese J, Lamb FS, Breyer RM. Regulation of arterial reactivity by concurrent signaling through the E-prostanoid receptor 3 and angiotensin receptor 1. Vascul. Pharmacol [print-electronic]. 2016 Sep; 84: 47-54. PMID: 27260940, PMCID: PMC4976016, PII: S1537-1891(16)30016-7, DOI: 10.1016/j.vph.2016.05.015, ISSN: 1879-3649.

Koch SR, Lamb FS, Hellman J, Sherwood ER, Stark RJ. Potentiation and tolerance of toll-like receptor priming in human endothelial cells. Transl Res [print-electronic]. 2016 Aug 8/8/2016; PMID: 27567430, PII: S1931-5244(16)30158-X, DOI: 10.1016/j.trsl.2016.08.001, ISSN: 1878-1810.

Stark RJ, Choi H, Koch SR, Fensterheim BA, Lamb FS, Sherwood ER. Endothelial cell tolerance to lipopolysaccharide challenge is induced by monophosphoryl lipid A. Clin. Sci [print-electronic]. 2016 Mar; 130(6): 451-61. PMID: 26669797, PMCID: PMC4744094, PII: CS20150592, DOI: 10.1042/CS20150592, ISSN: 1470-8736.

O'Lynnger TM, Shannon CN, Le TM, Greeno A, Chung D, Lamb FS, Wellons JC. Standardizing ICU management of pediatric traumatic brain injury is associated with improved outcomes at discharge. J Neurosurg Pediatr [print-electronic]. 2016 Jan; 17(1): 19-26. PMID: 26451717, DOI: 10.3171/2015.5.PEDS1544, ISSN: 1933-0715.

Choi H, Dikalova A, Stark RJ, Lamb FS. C-Jun N-terminal kinase attenuates TNFa signaling by reducing Nox1-dependent endosomal ROS production in vascular smooth muscle cells. Free Radic. Biol. Med [print-electronic]. 2015 Sep; 86: 219-27. PMID: 26001727, PII: S0891-5849(15)00226-9, DOI: 10.1016/j.freeradbiomed.2015.05.015, ISSN: 1873-4596.

Lamb FS. Localising oxidant "stress" in the antiphospholipid syndrome. Thromb. Haemost [print-electronic]. 2015 May; 113(5): 915. PMID: 25832773, PII: 15-03-0218, DOI: 10.1160/TH15-03-0218, ISSN: 0340-6245.

Choi H, Nguyen HN, Lamb FS. Inhibition of endocytosis exacerbates TNF-a-induced endothelial dysfunction via enhanced JNK and p38 activation. Am. J. Physiol. Heart Circ. Physiol [print-electronic]. 2014 Apr 4/15/2014; 306(8): H1154-63. PMID: 24561862, PII: ajpheart.00885.2013, DOI: 10.1152/ajpheart.00885.2013, ISSN: 1522-1539.

Agarwal HS, Hardison DC, Saville BR, Donahue BS, Lamb FS, Bichell DP, Harris ZL. Residual lesions in postoperative pediatric cardiac surgery patients receiving extracorporeal membrane oxygenation support. J. Thorac. Cardiovasc. Surg [print-electronic]. 2014 Jan; 147(1): 434-41. PMID: 23597724, PII: S0022-5223(13)00324-3, DOI: 10.1016/j.jtcvs.2013.03.021, ISSN: 1097-685X.

Garbrecht MR, Lamb FS. Placental HSD2 Expression and Activity Is Unaffected by Maternal Protein Consumption or Gender in C57BL/6 Mice. ISRN Endocrinol [electronic-print]. 2013; 2013: 867938. PMID: 23781346, PMCID: PMC3679810, DOI: 10.1155/2013/867938, ISSN: 2090-4630.

Ganapathi SB, Wei SG, Zaremba A, Lamb FS, Shears SB. Functional regulation of ClC-3 in the migration of vascular smooth muscle cells. Hypertension [print-electronic]. 2013 Jan; 61(1): 174-9. PMID: 23150504, PMCID: PMC3521842, PII: HYPERTENSIONAHA.112.194209, DOI: 10.1161/HYPERTENSIONAHA.112.194209, ISSN: 1524-4563.

Roghair RD, Volk KA, Lamb FS, Segar JL. Impact of maternal dexamethasone on coronary PGE(2) production and prostaglandin-dependent coronary reactivity. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2012 Sep 9/1/2012; 303(5): R513-9. PMID: 22832534, PMCID: PMC3468415, PII: ajpregu.00658.2011, DOI: 10.1152/ajpregu.00658.2011, ISSN: 1522-1490.

Lamb FS, Hook JS, Hilkin BM, Huber JN, Volk AP, Moreland JG. Endotoxin priming of neutrophils requires endocytosis and NADPH oxidase-dependent endosomal reactive oxygen species. J. Biol. Chem [print-electronic]. 2012 Apr 4/6/2012; 287(15): 12395-404. PMID: 22235113, PMCID: PMC3320989, PII: M111.306530, DOI: 10.1074/jbc.M111.306530, ISSN: 1083-351X.

Vucovich M, Ehinger N, Poole SD, Lamb FS, Reese J. Spontaneous Rhythmic Contractions (Vasomotion) of the Isolated, Pressurized Ductus Arteriosus of Preterm, but Not Term, Fetal Mice. EJ Neonatol Res. 2012 Jan; 2(1): 13-24. PMID: 23710420, PMCID: PMC3661283, ISSN: 2160-6072.

Roghair RD, Wemmie JA, Volk KA, Scholz TD, Lamb FS, Segar JL. Maternal antioxidant blocks programmed cardiovascular and behavioural stress responses in adult mice. Clin. Sci. 2011 Nov; 121(10): 427-36. PMID: 21615331, PMCID: PMC3677964, PII: CS20110153, DOI: 10.1042/CS20110153, ISSN: 1470-8736.

Chu X, Filali M, Stanic B, Takapoo M, Sheehan A, Bhalla R, Lamb FS, Miller FJ. A critical role for chloride channel-3 (CIC-3) in smooth muscle cell activation and neointima formation. Arterioscler. Thromb. Vasc. Biol [print-electronic]. 2011 Feb; 31(2): 345-51. PMID: 21071705, PMCID: PMC3025755, PII: ATVBAHA.110.217604, DOI: 10.1161/ATVBAHA.110.217604, ISSN: 1524-4636.

Bozeat ND, Xiang SY, Ye LL, Yao TY, Duan ML, Burkin DJ, Lamb FS, Duan DD. Activation of volume regulated chloride channels protects myocardium from ischemia/reperfusion damage in second-window ischemic preconditioning. Cell. Physiol. Biochem [print-electronic]. 2011; 28(6): 1265-78. PMID: 22179014, PMCID: PMC3709186, PII: 000335858, DOI: 10.1159/000335858, ISSN: 1421-9778.

Matsuda JJ, Filali MS, Moreland JG, Miller FJ, Lamb FS. Activation of swelling-activated chloride current by tumor necrosis factor-alpha requires ClC-3-dependent endosomal reactive oxygen production. J. Biol. Chem [print-electronic]. 2010 Jul 7/23/2010; 285(30): 22864-73. PMID: 20479003, PMCID: PMC2906278, PII: M109.099838, DOI: 10.1074/jbc.M109.099838, ISSN: 1083-351X.

Volk KA, Roghair RD, Jung F, Scholz TD, Lamb FS, Segar JL. Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2010 Jun; 298(6): R1607-14. PMID: 20335378, PMCID: PMC2886704, PII: ajpregu.00824.2009, DOI: 10.1152/ajpregu.00824.2009, ISSN: 1522-1490.

Miller FJ, Chu X, Stanic B, Tian X, Sharma RV, Davisson RL, Lamb FS. A differential role for endocytosis in receptor-mediated activation of Nox1. Antioxid. Redox Signal. 2010 Mar 3/1/2010; 12(5): 583-93. PMID: 19737091, PMCID: PMC2861543, DOI: 10.1089/ars.2009.2857, ISSN: 1557-7716.

Matsuda JJ, Filali MS, Collins MM, Volk KA, Lamb FS. The ClC-3 Cl-/H+ antiporter becomes uncoupled at low extracellular pH. J. Biol. Chem [print-electronic]. 2010 Jan 1/22/2010; 285(4): 2569-79. PMID: 19926787, PMCID: PMC2807314, PII: M109.018002, DOI: 10.1074/jbc.M109.018002, ISSN: 1083-351X.

Lamb FS, Moreland JG, Miller FJ. Electrophysiology of reactive oxygen production in signaling endosomes. Antioxid. Redox Signal. 2009 Jun; 11(6): 1335-47. PMID: 19207039, PMCID: PMC2872256, PII: 10.1089/ARS.2009.2448, DOI: 10.1089/ARS.2009.2448, ISSN: 1557-7716.

von Bergen NH, Koppenhafer SL, Spitz DR, Volk KA, Patel SS, Roghair RD, Lamb FS, Segar JL, Scholz TD. Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria. Clin. Sci. 2009 Apr; 116(8): 659-68. PMID: 19032144, PMCID: PMC3677965, PII: CS20080474, DOI: 10.1042/CS20080474, ISSN: 1470-8736.

Roghair RD, Segar JL, Volk KA, Chapleau MW, Dallas LM, Sorenson AR, Scholz TD, Lamb FS. Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2009 Mar; 296(3): R651-62. PMID: 19144750, PMCID: PMC2665850, PII: 90756.2008, DOI: 10.1152/ajpregu.90756.2008, ISSN: 0363-6119.

Volk AP, Heise CK, Hougen JL, Artman CM, Volk KA, Wessels D, Soll DR, Nauseef WM, Lamb FS, Moreland JG. ClC-3 and IClswell are required for normal neutrophil chemotaxis and shape change. J. Biol. Chem [print-electronic]. 2008 Dec 12/5/2008; 283(49): 34315-26. PMID: 18840613, PMCID: PMC2590705, PII: M803141200, DOI: 10.1074/jbc.M803141200, ISSN: 0021-9258.

Roghair RD, Miller FJ, Scholz TD, Lamb FS, Segar JL. Coronary constriction to angiotensin II is enhanced by endothelial superoxide production in sheep programmed by dexamethasone. Pediatr. Res. 2008 Apr; 63(4): 370-4. PMID: 18356741, PMCID: PMC3663587, PII: 00006450-200804000-00007, DOI: 10.1203/PDR.0b013e3181659bfa, ISSN: 0031-3998.

Matsuda JJ, Filali MS, Volk KA, Collins MM, Moreland JG, Lamb FS. Overexpression of CLC-3 in HEK293T cells yields novel currents that are pH dependent. Am. J. Physiol., Cell Physiol [print-electronic]. 2008 Jan; 294(1): C251-62. PMID: 17977943, PII: 00338.2007, DOI: 10.1152/ajpcell.00338.2007, ISSN: 0363-6143.

George CL, Goss KL, Meyerholz DK, Lamb FS, Snyder JM. Surfactant-associated protein A provides critical immunoprotection in neonatal mice. Infect. Immun [print-electronic]. 2008 Jan; 76(1): 380-90. PMID: 17967856, PMCID: PMC2223658, PII: IAI.01043-07, DOI: 10.1128/IAI.01043-07, ISSN: 1098-5522.