Vanderbilt University School of Medicine

Flynn, Charles Robert , PhD
Assistant Professor of Surgery

Lab Url: N/A

Phone Number: (615) 343-8329


Flynn, Charles's picture

Office Address   Mailing Address

MRB IV Langford Hall 8465A

4303 Medical Center North; 2211 Garland Ave; 37232-2736

Research Keywords
Proteomics Lipidomics Cell and Molecular Biology,Diabetes,Mass spectroscopy,Phosphorylation

Research Description
My research program focuses on understanding the cellular and molecular mechanisms contributing to obesity, insulin resistance and the Metabolic Syndrome. Contributory to the pathophysiology of these diseases are the many roles of adipose tissue, lipid metabolism, and the regulation of lipid droplet formation and trafficking. Obesity is a very important factor in the devlopment of diabetes. At present, the only treatment for morbid obesity proven to be consistently effective over the long term is bariatric surgery. Interestingly, the Type 2 Diabetes that is frequently a comorbidity in these patients, is resolved after surgery, frequently before weight loss occurs. The reasons for this are not known. We use powerful mass spectrometry-based lipidomics and proteomics techniques to profile human adipose and muscle biopsies acquired before and after dramatic weight loss. The relative expression changes of select lipids and proteins gleaned from these analyses are correlated with various clinical parameters and validated in model cell culture systems. The methodologies and approaches we use in cell culture are varied, but include stable isotopic labeling, live cell imaging, fluorescent protein and siRNA expression along with traditional biochemistry. The long term aim of our studies is to design cell permeable peptide and/or lipid mimetics of candidate markers identified through metabolic profiling that could be used in the restoration of desired metabolic phenotypes.

Breitman, I, Isbell, JM, Saliba, J, Jabbour, K, Flynn, CR, Marks-Shulman, PA, Laferrere, B, Abumrad, NN, Tamboli, RA. Effects of proximal gut bypass on glucose tolerance and insulin sensitivity in humans. , 5(36), e57, 2013.

Osgood, MJ, Flynn, CR, Komalavilas, P, Brophy, C. Cell-permeant peptide inhibitors of vasospasm and intimal hyperplasia. Vascular, 21(1), 46-53, 2013.

Wattacheril, J, Seeley, EH, Angel, P, Chen, H, Bowen, BP, Lanciault, C, Caprioli RM, Abumrad, N, Flynn, CR.. Differential Intrahepatic Phospholipid Zonation in Simple Steatosis and Nonalcoholic Steatohepatitis. PLoS One, 2(8), e57165, 2013.

Dunn, JP, Abumrad, NN, Breitman, I, Marks-Shulman, PA, Flynn, CR, Jabbour, K, Feurer, ID, Tamboli, RA. Hepatic and peripheral insulin sensitivity and diabetes remission at 1 month after Roux-en-Y gastric bypass surgery in patients randomized to omentectomy. Diabetes Care, 35(1), 137-42, 2012.

Flynn, C, Zheng, S, Yan, L, Hedges, L, Womack, B, Fessel, J, Cogan, J, Austin, E, Loyd, J, West, J, Zhao, Z, Hamid, R. Connectivity map analysis of nonsense-mediated decay-positive BMPR2-related hereditary pulmonary arterial hypertension provides insights into disease penetrance. Am J Respir Cell Mol Biol, 47(1), 20-7, 2012.

Tamboli, RA, Hajri, T, Jiang, A, Marks-Shulman, PA, Williams, DB, Clements, RH, Melvin, W, Bowen, BP, Shyr, Y, Abumrad, NN, Flynn, CR. Reduction in inflammatory gene expression in skeletal muscle from Roux-en-Y gastric bypass patients randomized to omentectomy. PLoS One, 6(12), e28577, 2011.

Young, NA, Vuong, J, Flynn, C, Teskey, GC. Optimal parameters for microstimulation derived forelimb movement thresholds and motor maps in rats and mice. J Neurosci Methods, 196(1), 60-9, 2011.

Flynn CR, Cheung-Flynn J, Smoke CC, Lowry D, Roberson R, Sheller, MR, Brophy CM. The mechanisms of transduction of an anti-fibrotic peptide, AZX100 into human dermal keloid fibroblasts. J Pharm Sci, 99(7), 3100-21, 2010.

Flynn, CR, Cheung-Flynn, J, Smoke, CC, Lowry, D, Roberson, R, Sheller, MR, Brophy, CM. Internalization and intracellular trafficking of a PTD-conjugated anti-fibrotic peptide, AZX100, in human dermal keloid fibroblasts. J Pharm Sci, 99(7), 3100-21, 2010.

Hwang H, Bowen BP, Lefort N, Flynn CR, De Filippis EA, Roberts C, Smoke CC, Meyer C, Hojlund K, Yi Z, Mandarino LJ . Proteomics Analysis of Human Skeletal Muscle Reveals Novel Abnormalities in Obesity and Type 2 Diabetes Mellitus. Diabetes, 59(1), 33-42, 2010.

Dreiza CM, Komalavilas P, Furnish EJ, Flynn CR, Sheller MR, Smoke, CC Lopes LB, Brophy CM . The Small Heat Shock Protein 20, HSPB6, in muscle function and disease. Cell Stress and Chaperones, 15(1), 1-11, 2009.

Lefort N, Yi Z, Bowen B, Glancy B, De Filippis EA, Mapes R, Hwang H, Flynn CR, Willis WT, Civitarese A, Hojlund K, Mandarino LJ. Proteome Profile of Functional Mitochondria From Human Skeletal Muscle Using One-Dimensional Gel Electrophoresis and HPLC-ESI-MS/MS. J Proteomics, 72 (6), 1046-60, 2009.

Lopes, LB, Furnish, EJ, Komalavilas, P, Flynn, CR, Ashby, P, Hansen, A, Ly, DP, Yang, GP, Longaker, MT, Panitch, A, Brophy, CM. Cell Permeant Peptide Analogues of the Small Heat Shock Protein, HSP20, Reduce TGF-beta1-Induced CTGF Expression in Keloid Fibroblasts. J Invest Dermatol, 3(129), 590-598, 2009. PMCID:2740368

H??jlund, K, Yi, Z, Hwang, H, Bowen, B, Lefort, N, Flynn, CR, Langlais, P, Weintraub, ST, Mandarino, LJ. Characterization of the human skeletal muscle proteome by one-dimensional gel electrophoresis and HPLC-ESI-MS/MS. Mol Cell Proteomics, 7(2), 257-67, 2008.

Komalavilas, P, Penn, RB, Flynn, CR, Thresher, J, Lopes, LB, Furnish, EJ, Guo, M, Pallero, MA, Murphy-Ullrich, JE, Brophy, CM. The small heat shock-related protein, HSP20, is a cAMP-dependent protein kinase substrate that is involved in airway smooth muscle relaxation. Am J Physiol Lung Cell Mol Physiol, 294(1), L69-78, 2008. PMCID:2757925

Flynn, CR, Smoke, CC, Furnish, E, Komalavilas, P, Thresher, J, Yi, Z, Mandarino, LJ, Brophy, CM. Phosphorylation and activation of a transducible recombinant form of human HSP20 in Escherichia coli. Protein Expr Purif, 52(1), 50-8, 2007. PMCID:1839877

Yi, Z, Langlais, P, De Filippis, EA, Luo, M, Flynn, CR, Schroeder, S, Weintraub, ST, Mapes, R, Mandarino, LJ. Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle. Diabetes, 56(6), 1508-16, 2007.

Mullen RT, McCartney AW, Flynn, CR, Smith GS. Peroxisome Biogenesis and the formation of multivesicular peroxisomes during tombusvirus infection: A role for ESCRT?. Can J Bot, 8(84), 551-564, 2006.

Boles, JA, Kott, RW, Hatfield, PG, Bergman, JW, Flynn, CR. Supplemental safflower oil affects the fatty acid profile, including conjugated linoleic acid, of lamb. J Anim Sci, 83(9), 2175-81, 2005.

Flynn CR, Heinze M, Schumann U, Gietl, C. and Trelease, R.N. . AtPex10p, a putative Arabidopsis peroxin homolog, likely functions in subdomain(s) of ER as an early peroxin in peroxisomal biogenesis.. Plant Sci, 168, 635-652, 2005.

Flynn, CR, Brophy, CM, Furnish, EJ, Komalavilas, P, Tessier, D, Thresher, J, Joshi, L. Transduction of phosphorylated heat shock-related protein 20, HSP20, prevents vasospasm of human umbilical artery smooth muscle. J Appl Physiol, 98(5), 1836-45, 2005.

Lopes, LB, Brophy, CM, Furnish, E, Flynn, CR, Sparks, O, Komalavilas, P, Joshi, L, Panitch, A, Bentley, MV. Comparative study of the skin penetration of protein transduction domains and a conjugated peptide. Pharm Res, 22(5), 750-7, 2005.

Joshi L, Shah MM, Flynn CR, Panitch A. Post-translational Modifications and their roles in plant-produced recombinant therapeutic proteins.. In Encyclopedia of Plant and Crop Science, (4), 1-4, 2004.

Joshi L, Shah MM, Flynn CR, Panitch A. Plant-Produced Recombinant Therapeutics. In Encyclopedia of Plant and Crop science, 4, 969-972, 2004.

McLemore, EC, Tessier, DJ, Flynn, CR, Furnish, EJ, Komalavilas, P, Thresher, JS, Joshi, L, Stone, WM, Fowl, RJ, Brophy, CM. Transducible recombinant small heat shock-related protein, HSP20, inhibits vasospasm and platelet aggregation. Surgery, 136(3), 573-8, 2004.

Puffenberger, EG, Hu-Lince, D, Parod, JM, Craig, DW, Dobrin, SE, Conway, AR, Donarum, EA, Strauss, KA, Dunckley, T, Cardenas, JF, Melmed, KR, Wright, CA, Liang, W, Stafford, P, Flynn, CR, Morton, DH, Stephan, DA. Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function. Proc Natl Acad Sci U S A, 101(32), 11689-94, 2004. PMCID:511011

Flynn, CR, Komalavilas, P, Tessier, D, Thresher, J, Niederkofler, EE, Dreiza, CM, Nelson, RW, Panitch, A, Joshi, L, Brophy, CM. Transduction of biologically active motifs of the small heat shock-related protein HSP20 leads to relaxation of vascular smooth muscle. FASEB J, 17(10), 1358-60, 2003.

Shah, MM, Fujiyama, K, Flynn, CR, Joshi, L. Sialylated endogenous glycoconjugates in plant cells. Nat Biotechnol, 21(12), 1470-1, 2003.

Mullen, RT, Flynn, CR, Trelease, RN. How are peroxisomes formed? The role of the endoplasmic reticulum and peroxins. Trends Plant Sci, 6(6), 256-61, 2001.

Mullen, RT, Lisenbee, CS, Flynn, CR, Trelease, RN. Stable and transient expression of chimeric peroxisomal membrane proteins induces an independent "zippering" of peroxisomes and an endoplasmic reticulum subdomain. Planta, 213(6), 849-63, 2001.

Flynn, CR, Mullen, RT, Trelease, RN. Mutational analyses of a type 2 peroxisomal targeting signal that is capable of directing oligomeric protein import into tobacco BY-2 glyoxysomes. Plant J, 16(6), 709-20, 1998.

Mullen, RT, Lee, MS, Flynn, CR, Trelease, RN. Diverse amino acid residues function within the type 1 peroxisomal targeting signal. Implications for the role of accessory residues upstream of the type 1 peroxisomal targeting signal. Plant Physiol, 115(3), 881-9, 1997. PMCID:158551

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