Charles Robert Flynn, Ph.D.

Assistant Professor
Faculty Appointments
Assistant Professor of Surgery
Ph.D., Molecular and Cellular Biology, Arizona State University, Tempe, ArizonaB.S., Biochemistry, Montana State University, Billings, Montana
Office Address
4303 Medical Center North;
2211 Garland Ave;
8465A Langford Hall
Nashville, TN 37232-2736
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.
Research Keywords
metabolism, obesity, lipidomics, proteomics, bile acids, cell imaging
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. 2015.

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. 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. 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. 2015.

Guo Y, Xiong Y, Flynn CR. A Micro-RNA Expression Signature of Human NAFLD Progression. 2015.

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 [print-electronic]. 2014 Aug 8/1/2014; 21(4): 551-64. PMID: 24252090, PMCID: PMC4085980, DOI: 10.1089/ars.2013.5420, ISSN: 1557-7716.

Guo Y, Zhao S, Su PF, Li CI, Ye F, Flynn CR, Shyr Y. Statistical strategies for microRNAseq batch effect reduction. Transl Cancer Res. 2014 Jun 6/1/2014; 3(3): 260-5. PMID: 25258704, PMCID: PMC4171948, DOI: 10.3978/j.issn.2218-676X.2014.06.05, ISSN: 2218-676X.

Osgood MJ, Flynn CR, Komalavilas P, Brophy C. Cell-permeant peptide inhibitors of vasospasm and intimal hyperplasia. Vascular [print-electronic]. 2013 Feb; 21(1): 46-53. PMID: 23104826, PMCID: PMC4180429, PII: vasc.2011.201203, DOI: 10.1258/vasc.2011.201203, ISSN: 1708-5381.

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. 2013.

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. 2013.

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 [print-electronic]. 2012 Jul; 47(1): 20-7. PMID: 22312021, PMCID: PMC3402799, PII: rcmb.2011-0251OC, DOI: 10.1165/rcmb.2011-0251OC, ISSN: 1535-4989.

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 [print-electronic]. 2012 Jan; 35(1): 137-42. PMID: 22040841, PMCID: PMC3241322, PII: dc11-1383, DOI: 10.2337/dc11-1383, ISSN: 1935-5548.

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 [print-electronic]. 2011; 6(12): e28577. PMID: 22194858, PMCID: PMC3241684, PII: PONE-D-11-17236, DOI: 10.1371/journal.pone.0028577, ISSN: 1932-6203.

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. 2010 Dec 12/22/2010; 40(6): 893-904. PMID: 21172655, PMCID: PMC3266626, PII: S1097-2765(10)00969-X, DOI: 10.1016/j.molcel.2010.12.013, ISSN: 1097-4164.

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. 2010 Jul; 99(7): 3100-21. PMID: 20140957, DOI: 10.1002/jps.22087, ISSN: 1520-6017.

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. 2010; 59((1)): 33-42.

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. 2010; 99((7)): 3100-21.

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 [print-electronic]. 2009 Mar; 129(3): 590-8. PMID: 18787533, PMCID: PMC2740368, PII: jid2008264, DOI: 10.1038/jid.2008.264, ISSN: 1523-1747.

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. 2009; 15((1)): 1-11.

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. 2009; 72((6)): 1046-60.

Højlund 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 [print-electronic]. 2008 Feb; 7(2): 257-67. PMID: 17911086, PMCID: PMC3836591, PII: M700304-MCP200, DOI: 10.1074/mcp.M700304-MCP200, ISSN: 1535-9484.

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 [print-electronic]. 2008 Jan; 294(1): L69-78. PMID: 17993590, PMCID: PMC2757925, PII: 00235.2007, DOI: 10.1152/ajplung.00235.2007, ISSN: 1040-0605.

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 [print-electronic]. 2007 Jun; 56(6): 1508-16. PMID: 17360977, PII: db06-1355, DOI: 10.2337/db06-1355, ISSN: 1939-327X.

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 [print-electronic]. 2007 Mar; 52(1): 50-8. PMID: 17084643, PMCID: PMC1839877, PII: S1046-5928(06)00263-4, DOI: 10.1016/j.pep.2006.08.015, ISSN: 1046-5928.

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. 2006 May; 22(5): 479-83. PMID: 16651155, PII: S0749-8063(05)01805-0, DOI: 10.1016/j.arthro.2005.12.032, ISSN: 1526-3231.

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. 2006; 8((84)): 551-64.

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. 2005 Sep; 83(9): 2175-81. PMID: 16100073, PII: 83/9/2175, ISSN: 1525-3163.

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 [print-electronic]. 2005 May; 22(5): 750-7. PMID: 15906170, DOI: 10.1007/s11095-005-2591-x, ISSN: 0724-8741.

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. 2005 May; 98(5): 1836-45. PMID: 15829720, PII: 98/5/1836, DOI: 10.1152/japplphysiol.01043.2004, ISSN: 8750-7587.

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. 2005; 168: 635-52.

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. 2004 Sep; 136(3): 573-8. PMID: 15349104, PII: S0039606004001965, DOI: 10.1016/j.surg.2004.04.024, ISSN: 0039-6060.

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 [print-electronic]. 2004 Aug 8/10/2004; 101(32): 11689-94. PMID: 15273283, PMCID: PMC511011, PII: 0401194101, DOI: 10.1073/pnas.0401194101, ISSN: 0027-8424.

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. 2004; ((4)): 1-4.

Joshi L, Shah MM, Flynn CR, Panitch A. Plant-Produced Recombinant Therapeutics. In Encyclopedia of Plant and Crop science. 2004; 4: 969-72.

Shah MM, Fujiyama K, Flynn CR, Joshi L. Sialylated endogenous glycoconjugates in plant cells. Nat. Biotechnol [print-electronic]. 2003 Dec; 21(12): 1470-1. PMID: 14608367, PII: nbt912, DOI: 10.1038/nbt912, ISSN: 1087-0156.

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 [print-electronic]. 2003 Jul; 17(10): 1358-60. PMID: 12738803, PII: 02-1028fje, DOI: 10.1096/fj.02-1028fje, ISSN: 1530-6860.

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. 2001 Oct; 213(6): 849-63. PMID: 11722121, ISSN: 0032-0935.

Mullen RT, Flynn CR, Trelease RN. How are peroxisomes formed? The role of the endoplasmic reticulum and peroxins. Trends Plant Sci. 2001 Jun; 6(6): 256-61. PMID: 11378467, PII: S1360-1385(01)01951-3, ISSN: 1360-1385.

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. 1998 Dec; 16(6): 709-20. PMID: 10069077, ISSN: 0960-7412.

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. 1997 Nov; 115(3): 881-9. PMID: 9390426, PMCID: PMC158551, PII: 115/3/881, ISSN: 0032-0889.