David L. Williams, Ph.D. - Sepsis, inflammation and innate immunity

   Research Team

Welcome to the Williams Laboratory Home Page. We created this website to provide an overview of the research currently underway in our laboratory. Please feel free to browse through our website. If you have any questions or comments you may contact Dr. Williams at the address below.  


David L. Williams, Ph.D., Professor, Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0575, phone (423) 439-6363, fax (423) 439-6259.

Research Interests

Recent Publications 

Burt R,  Graves BM, Gao M, Li C, Williams DL, Fregoso SP, Hoover DB, Li Y, Wright GL, Wondergem R.  9-Phenanthrol and flufenamic acid inhibit calcium oscillations in HL-1 mouse cardiomyocytes.  Cell Calcium.  54(2013): 193-201;  Jul 4, 2013.  Pii: S0143-4160(13)00088-2.  doi: 10.1016/j.ceca.2013.06.003. 

Ifrim DC, Quintin J, Joosten LAB, Jacobs L, Jansen T, Gow N, Williams D, van der Meer JWM, Netea MG.  Trained Immunity or Tolerance: Opposing Functional Programs Induced in Human Monocytes after Engagement of Various Pattern Recognition Receptors.  Clinical Vaccine Immunology 2014, 21(4):534.

Kelley JL, Ozment TR, Li C, Schweitzer JB, Williams DL.  Scavenger Receptor-A (CD204): A Two-Edged Sword in Health and Disease.  Critical Reviews in Immunology, 34(3):241-261, 2014.

Li J, Zhang Y, Li C, Xie J, Liu Y, Zhu W, Zhang X, Jiang S, Liu L, Ding Z.  HSPA12B attenuates cardiac dysfunction and remodelling after myocardial infarction through an eNOS-dependent mechanism.  Cardiovascular Research, In Press, doi: 10.1093/cvr/cvt139, 2013.

Lowman DW, Greene RR, Bearden DW, Kruppa MD, Pottier M, Monteiro MA, Soldatov DV, Ensley HE, Cheng SC, Netea MG, Williams DL.  Novel structural features in Candida albicans hyphal glucan provide a basis for differential innate immune recognition of hyphae versus yeast.  Journal of Biological Chemistry, 289(6):3432-3443; doi: 10.1074/jbc.M113.529131, 12/16/2013.

Lu C, Ren D, Wang X, Ha T, Liu L, Lee EJ, Hu J, Kalbfleisch J, Gao X, Kao R, Williams D, Li C.  Toll-like receptor 3 plays a role in myocardial infarction and ischemia/reperfusion injury.  BBA-Molecular Basis of Disease 1842(1): 22-31, 2014.

Lu C, Ha T, Wang X, Liu L, Zhang X, Kimbrough EO, Sha Z, Guan M, Schweitzer J, Kalbfleisch J, Williams D, Li C.  The TLR9 Ligand, CpG-ODN, Induces Protection against Cerebral Ischemia/Reperfusion Injury via Activation of PI3K/Akt Signaling.  J Am Heart Assoc. 2014;3:e000629. 

Suram S, Silveira LJ, Mahaffey S, Brown GD, Bonventre JV, Williams DL, Gow NA, Bratton DL, Murphy RC, Leslie CC.  Cytosolic phospholipase s2a and eicosanoids regulate expression of genes in macrophages involved in host defense and inflammation.  PLoS One 8(7):e69002, 7/25/13.  PMC3742295.

Wang X, Ha T, Zou J, Ren D, Liu L, Zhang X, Kalbfleisch J, Gao X, Williams D, Li C.  MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signaling and TRAF6.  Cardiovasc Res, 2014 Mar. 10 (Epub ahead of print).

West L, Lowman DW, Mora-Montes HM, Grubb S, Murdoch C, Thornhill MH, Gow NA, Williams D, Haynes K.  Differential virulence of Candida glabrata glycosylation mutants.  J Biol Chem 288(30):22006-22018, 7/26/13. PMC3724654.

Zhang X, Lu C, Gao M, Cao X, Ha T, Kalbfleisch JH, Williams DL, Li C, Kao RL.  Toll-Like Receptor 4 Plays a Central Role in Cardiac Dysfunction During Trauma Hemorrhage Shock.  Shock, 2014 Feb 24 (Epub ahead of print).

Cao Z, Ren D, Ha T, Liu L, Wang X, Kalbfleisch J, Gao X, Kao R, Williams D, Li C.  CpG-ODN, the TLR9 agonist, attenuates myocardial ischemia/reperfusion injury: Involving activation of PI3K/Akt signaling.  Biochim Biophys Acta 1832(1) 96-104, 2013.

Gao M, Ha T, Zhang X, Liu L, Wang X, Kelley J, Singh K, Kao R, Gao X, Williams D, Li C.  Toll-like receptor 3 plays a central role in cardiac dysfunction during polymicrobial sepsis.  Crit Care Med  40(8):2390-2399, 2012.

Gao M, Ha T, Zhang X, Wang X, Liu L, Kalbfleisch J, Singh K, Williams D, Li C.  The TLR9 ligand, CpG-ODN attenuates cardiac dysfunction in polymicrobial sepsis: involving activation of both PI3K/Akt and ERK signaling.  Journal of Infectious Diseases 2013, May; 207(9):1471-1479.

Graves BM, Simerly T, Li C, Williams DL, Wondergem R.  Phosphoinositide-3-kinase/Akt-dependent signaling is required for maintenance of [Ca2+]I, Ica, and CA2+ transients in HL-1 cardiomyocytes.  J Biomed Sci 19(1): 59, 2012.

Ifrim DC, Joosten LA, Kullberg BJ, Jacobs L, Jansen T, Williams DL, Gow NA, van der Meer JW, Netea MG, Quintin J.  Candida albicans Primes TLR Cytokine Responses through a Dectin-1/Raf-1-Mediated Pathway.  J Immunol.  2013 Apr 15.  190(8): 4129-4135.

Li C, Hua F, Ha T, Singh K, Lu C, Kalbfleisch J, Breuel KF, Ford T, Kao RL, Gao M, Ozment TR, Williams DL.  Activation of myocardial phosphoinositide-3-kinase p110α ameliorates cardiac dysfunction and improves survival in polymicrobial sepsis.  PLoS ONE, 2012; 7(9):e44712.

Lowman DW, West LJ, Bearden DW, Wempe MF, Power TD, Ensley HE, Haynes K, Williams DL, Kruppa MD.  New Insights into the Structure of (1-3, 1-6)-β-D-Glucan Side Chains in the Candida glabrata Cell Wall.  PLoS ONE, 6(11):327614 (epub).

Marakalala MJ, Williams DL, Hoving JC, Engstad R, Netea MG, Grown GD.  Dectin-1 plays a redundant role in the immunomodulatory activities of β-glucan-rich ligands in vivo.  Microbes and Infection.  2013 Mar 19.  Epub ahead of press.

Ozment T, Goldman M, Kalbfleisch J, Williams D.  Soluble glucan is internalized and trafficked to the Golgi apparatus in macrophages via a clathrin mediated lipid raft regulated mechanism.  Journal of Pharmacology and Experimental Therapeutics, 342(3): 808-815, 2012.

Ozment TR, Ha T, Breuel KF, Ford TR, Ferguson DA, Kalbfleisch J, Schweitzer JB, Kelley JL, Li C, Williams DL.  Scavenger Receptor class A plays a central role in mediating mortality and the development of the pro-inflammatory phenotype in polymicrobial sepsis.  PLoS Pathogens, 8(10): e1002967 (epub).

Ren D, Wang X, Ha T, Liu L, Kalbfleisch J, Gao X, Williams D, Li C.  SR-A deficiency reduces myocardial ischemia/reperfusion injury; involvement of increased microRNA-125b expression in macrophages.  Biochimica et Biophysica Acta 1832(2013): 336-346.

Wang X, Ha T, Liu L, Zou J, Zhang X, Kalbfleisch J, Gao X, Williams D, Li D.  Increased expression of microRNA-146a decreases myocardial ischemia/reperfusion injury.  Cardiovascular Research, 2013 Mar 1; 97(3):432-442.

Wondergem R, Graves BM, Li C, Williams DL.  Lipopolysaccharide prolongs action potential duration in HL-1 mouse cardiomyocytes.  Am J Physiol Cell Physiol 303:C825-C833, 2012.

Zhang X, Gao M, Ha T, Kalbfleisch JH, Williams DL, Li C, Kao RL.  The Toll-Like Receptor 9 Agonist, CPG-Oligodeoxynucleotide 1826, Ameliorates Cardiac Dysfunction After Trauma-Hemorrhage.  Shock 38(2):146-152, 2012.

Ha T, Xia Y, Liu X, Lu C, Liu L, Kelley J, Kalbfleisch J, Kao RL, Williams DL, Li C.  Glucan phosphate attenuates myocardial HMGB1 translocation in severe sepsis through inhibiting NF-kB activation.  Am J Physiol Heart Circ Physiol 301(3):H848-55, 2011.

Ha T, Liu L, Kelley J, Kao R, Williams D, Li C.  Toll-like receptors: new players in myocardial ischemia/reperfusion injury.  Antioxid Redox Signal 15(7):1875-1893, 10/1/2011.

Kruppa M, Greene RR, Noss I, Lowman DW, Williams DL.  C. albicans increases cell wall mannoprotein, but not mannan, in response to blood, serum and cultivation at physiological temperature.  Glycobiology 21(9):1173-1180, 2011.

Lowman DW, Ensley HE, Greene RR, Knagge KJ, Williams DL, Kruppa MD.  Mannan structural complexity is decreased when Candida albicans is cultivated in blood or serum at physiological temperature.  Carbohydrate Research 346 (2011):2752-2759.

Lu C, Liu L, Chen Y, Ha T, Kelley J, Schweitzer J, Kalbfleisch JH, Kao RL, Williams DL, Li C.  TLR2 Ligand Induces Protection against Cerebral Ischemia/Reperfusion Injury via Activation of Phosphoinositide 3-Kinase/Akt Signaling.  The Journal of Immunology, 6/27/2011, doi:10.4049/jimmunol.1003428. J Immunol 187(3):1458-1466. 8/1/2011.

Ozment TR, Goldman MP, Kalbfleisch JH, Williams DL.  Soluble glucan is internalized and trafficked to the Golgi apparatus in macrophages via a clathrin mediated, lipid raft regulated mechanism.  Journal of Pharmacology and Experimental Therapeutics, ePub 6/13/2012.

Smeekens SP, van de Veerdonk FL, Joosten LA, Jacobs L, Jansen T, Williams DL, van der Meer JW, Kullberg BJ, Netea MG.  The classical CD14(++) CD16 (-) monocytes, but not the patrolling CD14(+) CD16 (+) monocytes, promote Th17 responses to Candida albicans.  Eur J Immunol, 41(10):2915-24.  Epub 2011 Aug 30.

Wu H, Gao M, Ha T, Kelley J, Young A, Breuel K.  Prunella vulgaris aqueous extract attenuates IL-1β-induced apoptosis and NF-kB activation in INS-1 Cells.  Experimental and Therapeutic Medicine, 2012 In Press.

Yu H, Ha T, Liu L, Wang X, Gao M, Kelley J, Kao R, Williams D, Li C.  Scavenger receptor A (SR-A) is required for LPS-induced TLR4 mediated NF-kB activation in macrophages.  Biochimica et Biophysica Acta – Molecular Cell Research 1823(2012): 1192-1198, 2012.

Zhang X, Gao M, Ha T, Kalbfleisch JH, Williams DL, Li C, Kao RL.  The TLR9 Agonist, CpG-ODN 1826, Ameliorates Cardiac Dysfunction After Trauma-Hemorrhage.  Shock, May 9, 2012, Epub ahead of print.