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

Faculty Appointments
Professor of Pediatrics Professor of Molecular Physiology and BiophysicsCornelius Vanderbilt Chair
Ph.D., University of Michigan, Ann Arbor, MichiganM.D., MEDICINE, University of Michigan, Ann Arbor, MichiganB.S., University of Michigan, Ann Arbor, Michigan
Office Address
2200 Children's Way
Nashville, TN 37232
Research Description
Cytokines are critical drivers of inflammation, and important therapeutic targets in aggressive inflammatory conditions such as arthritis and colitis. They also drive more indolent inflammatory conditions such as hypertension and atherosclerosis, however safe and effective tools for long term modulation of cytokine signaling are lacking. Reactive oxygen produced by the Nox1 NADPH oxidase is required for signaling by TNFalpha, IL-1beta and for endotoxin signaling through TLR4 receptors. We have identified two types of anion transporters, the ClC-3 Cl-/H+ exchanger and the LRRC8 family of anion channels, which are required for superoxide production by Nox1. The long-term goal of the Lamb laboratory is to determine if anion transport can be pharmacologically targeted to modulate cytokine signaling and control inflammation. Our primary research focus is to determine mechanisms by which Nox1-derived superoxide supports signaling, define the functional relationship between anion transport and Nox1, and assess 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,
Rohrbough J, Nguyen HN, Lamb FS. Modulation of ClC-3 gating and proton/anion exchange by internal and external protons and the anion selectivity filter. J. Physiol. (Lond.) [print-electronic]. 2018 Sep; 596(17): 4091-119. PMID: 29917234, DOI: 10.1113/JP276332, ISSN: 1469-7793.

Stark RJ, Koch SR, Choi H, Mace EH, Dikalov SI, Sherwood ER, Lamb FS. Endothelial nitric oxide synthase modulates Toll-like receptor 4-mediated IL-6 production and permeability via nitric oxide-independent signaling. FASEB J [print-electronic]. 2018 Feb; 32(2): 945-56. PMID: 29061842, PMCID: PMC5888395, PII: fj.201700410R, DOI: 10.1096/fj.201700410R, ISSN: 1530-6860.

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.

Stark R, Choi H, Koch S, Lamb F, Sherwood E. Monophosphoryl lipid A inhibits the cytokine response of endothelial cells challenged with LPS. Innate Immun [print-electronic]. 2015 Aug; 21(6): 565-74. PMID: 25540284, PMCID: PMC4480205, PII: 1753425914564172, DOI: 10.1177/1753425914564172, ISSN: 1753-4267.

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.

Available Postdoctoral Position Details
Posted: 4/17/2018

We are looking for a highly motivated individual with electrophysiological training to study chloride ion currents and chloride transport in vascular smooth muscle cells from the ductus arteriosus using whole cell patch clamp and fluorescence imaging techniques. This is an NIH funded position. The qualified individual will work with a team of close collaborators to use a combination of whole-cell and perforated-patch techniques, tissue physiology and cell imaging techniques to characterize the involvement of anion channels and transporters in the oxygen-dependent closure of the ductus arteriosus at the time of birth. Persistent patency of this vascular structure, which bridges the systemic and pulmonary circulations in utero, is a very significant clinical problem, particularly in premature infants. This work seeks to identify novel approaches to pharmacologic manipulation of ductal patency.

Qualifications: Ph.D. in physiology, pharmacology, biophysics, or related field, with prior patch clamp experience. Excellent English language skills (both written and oral). Salary is commensurate with experience. Health and retirement benefits included.

Interested candidates should submit a letter of interest briefly describing their research experience and career goals, a current CV, and names and contact information of three references.

Fred S. Lamb MD, PhD