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,Endocrinology,Mass spectroscopy,Phosphorylation,Post-transcriptional modification,Proteomics

Research Specialty
metabolism, obesity, lipidomics, proteomics, bile acids, cell imaging

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 fully understood. 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. We have recently developed in mice an alternative bariatric procedure that is equally as effective as Roux-en-Y-Gastric Bypass (RYGB) but without intestinal rearrangement. We are characterizing this model to better undertand the mechanisms fundamental to nutrient absorption in the gut.

Flynn CR, Albaugh VL, Cai S, Cheung-Flynn J, Williams PE, Brucker RM, Bordenstein, SR, Wasserman DH, Abumrad, NN. Bile Diversion to the Distal But Not Proximal Small Intestine is Associated with Sustained Metabolic Benefits Comparable to Bariatric Surgery. Nature Communications, under review, , 2015.

Garcia AE, Kasim N, Dunn JP, Tamboli RA, Gonzalez R, Antoun J, Eckert EA, Marks-Shulman PA, Wattacheril J, Abumrad NN, Flynn CR. Lipoprotein Subfraction Metabolism and Nonalcoholic Fatty Liver Disease: a Baseline and Weight-loss Comparison. Journal of Hepatology, (under review), , 2015.

Guo Y, Xiong Y, Flynn CR. A Micro-RNA Expression Signature of Human NAFLD Progression. Journal of Gastroenterology and Hepatology, (under review), , 2015.

Kim S, Wu S, Baek J, Choi, SY, Su Y, Flynn CR, Gamse JT, Ess KC, Hardiman G, Lipshutz JH, Abumrad NN, Rockey DC. A Post-Developmental Genetic Screen for Zebrafish Models of Inherited Liver Disease. PLoS One, accepted, , 2015.

Wattacheril J, Rose, KL, Hill S, Lanciault C, Murray CR, Washington K, Williams B, Clements R, Abumrad N, Flynn CR. NAFLD Phosphoproteomics: A Functional Piece of the Precision Puzzle . Gastroenterology, (under review), , 2015.

Guo, Y, Zhao, S, Su, PF, Li, CI, Ye, F, Flynn, CR, Shyr, Y. Statistical strategies for microRNAseq batch effect reduction. Transl Cancer Res, 3(3), 260-265, 2014.

Vassilopoulos, A, Pennington, JD, Andresson, T, Rees, DM, Bosley, AD, Fearnley, IM, Ham, A, Flynn, CR, Hill, S, Rose, KL, Kim, HS, Deng, CX, Walker, JE, Gius, D. SIRT3 deacetylates ATP synthase F1 complex proteins in response to nutrient- and exercise-induced stress. Antioxid Redox Signal, 21(4), 551-64, 2014.

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.

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.

Tao, R, Coleman, MC, Pennington, JD, Ozden, O, Park, SH, Jiang, H, Kim, HS, Flynn, CR, Hill, S, Hayes McDonald, W, Olivier, AK, Spitz, DR, Gius, D. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell, 40(6), 893-904, 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.

Dunn, WR, Cordasco, FA, Flynn, E, Jules, K, Gordon, M, Liguori, G. A prospective randomized comparison of spinal versus local anesthesia with propofol infusion for knee arthroscopy. Arthroscopy, 22(5), 479-83, 2006.

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. Plant-Produced Recombinant Therapeutics. In Encyclopedia of Plant and Crop science, 4, 969-972, 2004.

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.

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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