Guðmundur Hrafn Guðmundsson

Gudmundur studied Biology at the University of Iceland (BS degree 1984). He completed his PhD on insect immunity in 1992 at the Department of Microbiology, University of Stockholm, with Hans G. Boman as a supervisor. In his postdoctoral work at the University of Stockholm and Karolinska Institutet (Microbiology and Tumor biology Center, MTC) the research was on mammalian innate immunity, 1992-1998.

GHG was appointed an Associate Professor in Immunology, Karolinska Institutet in 1999. In 2001 GHG became a professor of cell biology at the University of Iceland. In 1994 he discovered the human antimicrobial peptide LL-37 and most of his research activity has been on innate immunity in health and disease. In 1996 he was awarded Letterstedtskapriset from The Royal Swedish Academy of Sciences. GHG has published around 60 articles on antimicrobial peptides and innate immunity.

Current work is focused on regulation of innate immunity with emphasis on antimicrobial peptides (AMPs). Understanding epithelial responses upon endogenous stimulation or by external effectors is the aim. Further the composition of surface immunity in different tissues in health and upon challenge is studied. Inducers of AMP expression have been identified and are tested as potential drugs against infections.

Birgitta Agerberth group at MBB, Karolinska Institutet. Stockholm Sweden. Rubhana Raqib International Centre for Diarrheal Disease Research, Dhaka, Bangladesh.

The Gudmundsson group:

Carolin Huehnken PhD student

Nikhil N. Kulkarni PhD student

In chronological order

1. Lidholm D.-A., Gudmundsson G.H., Xanthopoulos K.G. & Boman H. G. (1987) Insect immunity: cDNA clones coding for the precursor forms of cecropins A and D, antibacterial proteins from Hyalophora cecropia. FEBS Lett. 22, 8-12.
2. Gudmundsson G.H., Lidholm D.-A., Åsling B., Gan R. B. & Boman H. G. (1991). The cecropin locus; cloning and expression of a gene cluster encoding three antibacterial peptides in Hyalophora cecropia. J. Biol. Chem., 266, 11510-11517.
3. Lidholm D.-A., Gudmundsson G.H., & Boman H.G. (1991). A highly repetitive, mariner-like element in the genome of Hyalophora cecropia. J. Biol. Chem. 266, 11518-11521.
4. Schlenstedt G., Gudmundsson G.H., Boman H.G. & Zimmermann R. (1990) A large presecretory protein translocates both cotranslationally, using signal recognition particle and ribosome, and posttranslationally, without these ribonucleoparticles, when synthesized in the presence of mammalian microsomes. J. Biol. Chem. 265, 13960-13968.
5. Schlenstedt G., Gudmundsson G.H., Boman H.G. & Zimmermann R. (1992). Structural requirements for transport of preprocecropin A and related presecretory proteins into mammalian microsomes. J. Biol. Chem. 267, 24328-24332.
6. Agerberth B., Gunne H., Odeberg J., Kogner P., Boman H.G. & Gudmundsson, G.H. (1995) FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Proc. Natl. Acad. Sci. USA, 92, 195-199.
7. Andersson M., Gunne H., Agerberth B., Boman A., Bergman T., Sillard R., Jörnvall H., Mutt V., Olsson B., Wigzell H., Dagerlind Å., Boman H.G. & Gudmundsson G.H. (1995) NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity. EMBO J., 15, 1615-1625.
8. Gudmundsson G.H., Magnusson K.P., Crowdary B.P., Johansson M., Andersson L. & Boman H.G. (1995) Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene family member; Comparative mapping of the locus for a human peptide antibiotic FALL-39. Proc. Natl. Acad. Sci. USA, 92, 7085-7089.
9. Gudmundsson G.H., Agerberth B., Odeberg J., Bergman T., Olsson B. & Salcedo, R. (1996). The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur. J. Biochem., 238, 325-332.
10. Andersson M., Agerberth B. & Gudmundsson G.H. (1996) Cytotoxic T lymphocytes: more weapons for new targets? Response. Trends in Microbiology 4, 94.
11. Frohm* M., Agerberth* B., Ahangari G., Ståhle-Bäckdahl M. Lidén S. Wigzell H. & Gudmundsson G.H. (1997) The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J. Biol. Chem., 272, 15258-15263. *Equal contribution
12. Johansson, J., Gudmundsson G.H., Rottenberg M.E., Berndt K.D. & Agerberth B. (1998) Conformation-dependent antibacterial activity of the naturally-occurring human peptide LL-37. J. Biol. Chem. 273, 3718-3724.
13. Odeberg J., Røsok Ø., Gudmundsson G.H., Roshani L., Larsson C., Uhlén M., Åsheim H-C. & Lundeberg J. (1998) Cloning and characterisationof ZNF189, a novel human Kruppel-like zinc finger gene localised to chromosome 9q22-31. Genomics 50, 213-221.
14. Agerberth B., Grunewald J., Castanos-Velez E., Olsson B., Jörnvall H., Wigzell H., Eklund A. & Gudmundsson G.H. (1999) Antibacterial components in bronchoalveolar lavage fluid from healthy individuals and sarcoidosis patients. Am. J. Respir. Crit. Care Med., 160, 283-290.
15. Oren, Z., Lerman, J.C., Gudmundsson, G.H., Agerberth, B. & Shai, Y. (1999) Structure and organization of the human antimicrobial peptide LL-37 in phospholipid  membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem. J., 341, 501-513.
16. Agerberth B., Charo J., Werr J., Olsson B., Idali F., Lindbom L., Kiessling R., Jörnvall H. Wigzell H. & Gudmundsson G.H. (2000) The human antimicrobial and chemotactic peptides LL-37 and a-defensins HNP 1-3 are expressed by specific lymphocyte and monocyte populations. BLOOD, 96, 3086-3093.
17. Islam D., Bandholtz L., Nilsson J., Wigzell H., Christensson B., Agerberth B. & Gudmundsson G.H. (2001) Downregulation of bactericidal peptides in enteric infections: A novel immune escape mechanism with bacterial DNA as a potential regulator. Nature Medicine, 7, 180-185.
18. Lensmar, C., Nord, M., Gudmundsson, G.H., Roquet, A., Andersson, O., Jörnvall, H., Eklund, A., Grunewald, J. & Agerberth, B. (2001) Decreased pulmonary levels of the anti-inflammatory Clara cell 16 kDa protein after induction of airway inflammation in asthmatics. Cell. Mol. Life Sci. 57, 976-981.
19. Dorschner, R.A., Pestonjamasp, V.K., Tamakuwala, S. Ohtake, T., Rudisill, J.,  Nizet, V.,  Agerberth, B., Gudmundsson, G.H. & Gallo, R.L. (2001) Cutaneous injury induces the release of cathelicidin antimicrobial peptides active against Group A Streptococcus. J. Invest. Dermatol. 117, 91-97.
20. Marchini, G., Lindow, S., Brismar, H., Ståbi, B., Berggren, V., Ulfgren, A-K., Lonne-Rahm, S., Agerberth, B. & Gudmundsson, G.H. (2002) The human neonate is protected by an antimicrobial barrier: Peptide antibiotics are present in the skin and vernix caseosa. Br. J. Dermatol. 147, 1127-1134.
21. Schauber, J., Svanholm, C., Termén, S., Iffland, K., Menzel, T., Scheppach, W., Melcher, R., Agerberth, B., Luhrs, H. & Gudmundsson, G.H. (2003) The expression of the cathelicidin LL-37 is modulated by short-chain fatty acids in colonocytes and leukocytes: Relevance of signaling pathways. Gut, 52, 735-749.
22. Abraham-Nordling, M., Gudmundsson, G.H., Grunewald, J., Agerberth, B. & Griffiths, W.J. (2003) Identification of a potent antibacterial factor isolated from bronchoalveolar lavage fluid: Guanidine, N-(3-((aminoiminomethyl)amino)propyl)-N-dodecyl-, a potential source of error in the analysis of antibacterial agents. Rapid Comm. Mass Spectrom. 17, 183-191.
23. Ericson K.G., Fadeel B., Andersson M., Gudmundsson G.H., Gurgey A., Yalman N., Janka G, Nordenskjold M, & Henter JI. (2003) Sequence analysis of the granulysin and granzyme B genes in familial hemophagocytic lymphohistiocytosis. Hum. Genet. 112, 98-9.
24. Yoshio H., Tollin M., Gudmundsson G.H., Lagercrantz H., Jörnvall H., Marchini G. & Agerberth B. (2003) Antimicropbial polypeptides of human vernix caseosa and amniotic fluid: Implications for newborn innate defense. Pediatr. Res. 53, 211-216.
25. Bandholtz, L., Guo, Y., Palmberg, C., Mattsson, K., Olsson, B., High, A., Shabanowitz, J., Hunt, D., Jörnvall, H., Wigzell, H., Agerberth*, B. & Gudmundsson*, G.H. (2003) Hsp90 binds CpG oligonucleotides directly, implications for hsp90 as a missing link in CpG signaling and recognition. Cell. Mol. Life Sci. 60, 422-429.*Equal contribution
26. Termén, S., Tollin, M., Olsson, B., Svenberg, T., Agerberth, B. and Gudmundsson, G.H. (2003) Phylogeny, processing and expression of the rat cathelicidin - A model for innate antimicrobial peptides. Cell. Mol. Life Sci. 60, 536-539.
27. Tollin, M., Bergman, P., Svenberg, T., Jörnvall, H., Gudmundsson, G.H. and Agerberth, B. (2003) Several antimicrobial polypeptides in the first line defence of human colon mucosa. Peptides 24, 523-530.
28. Yoshio H., Lagercrantz H., Gudmundsson G.H., Agerberth B. (2004) First line of defense in early human life. Semin Perinatol. 28, 304-11
29. Starner T.D., Agerberth, B., Gudmundsson, G.H. and McCray P. B. Jr. (2005) Expression and activity of beta-defensins and LL-37 in the developing human lung. J Immunol. 174, 1608-15
30. Bergmann, P., Termén S., Johanssson L., Nyström L., Arenas E., Jonsson A-B., Hökfelt T., Gudmundsson G.H., Agerberth B., (2005) The antimicrobial peptide rCRAMP is present in the central nervous system of the rat. J Neurochem. 93,1132-40.
31. Bergman, P., Johansson, L., Asp, V., Plant, L., Gudmundsson, G.H., Jonsson, AB., Agerberth, B. (2005) Neisseria gonorrhoeae downregulates expression of the human antimicrobial peptide LL-37. Cell Microbiol. 7, 1009-17.
32. Bergsson, G., Agerberth, B., Jornvall, H., Gudmundsson, G.H. (2005) Isolation and identification of antimicrobial components from the epidermal mucus of Atlantic cod (Gadus morhua). FEBS J. 272, 4960-9.
33. Tollin, M., Bergsson, G., Kai-Larsen, Y., Lengqvist, J., Sjovall, J., Griffiths, W., Skuladottir, G.V., Haraldsson, A., Jornvall, H., Gudmundsson, G.H., Agerberth, B. (2005) Vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions. Cell Mol Life Sci. 62, 2390-9.
34. Agerberth, B., Buentke, E., Bergman, P., Eshaghi, H., Gabrielsson, S., Gudmundsson, G.H., Scheynius, A. (2006) Malassezia sympodialis differently affects the expression of LL-37 in dendritic cells from atopic eczema patients and healthy individuals. Allergy. 61, 422-30.
35. Edfeldt K, Agerberth B, Rottenberg ME, Gudmundsson GH, Wang XB, Mandal K, Xu Q, Yan ZQ. (2006) Involvement of the Antimicrobial Peptide LL-37 in Human Atherosclerosis. Arterioscler Thromb Vasc Biol. 26: 1551-7
36. Raqib, R., Sarker, P., Bergman, P., Ara, G., Lindh, M., Sack, D.A., Nasirul, Islam, K.M., Gudmundsson, G.H., Andersson, J., Agerberth, B. (2006) Improved outcome in Shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proc. Natl. Acad. Sci. U S A. (2006) 103, 9178-83
37. Chromek, M., Slamová, Z., Bergman, P., Kovács, L., Podracká, L., Ehrén, I., Hökfelt, T., Gudmundsson, G.H., Gallo, R. L., Agerberth, B., Brauner A. (2006) The urinary tract is protected against invasive bacterial infection by rapid secretion of the cathelicidin antimicrobial peptide. Nature Medicine (2006) 12, 636-41
38. Bandholtz, L., Ekman, G.J., Vilhelmsson, M., Buentke, E., Agerberth, B., Scheynius, A., Gudmundsson, G.H. Antimicrobial peptide LL-37 internalized by immature human dendritic cells alters their phenotype. Scand J Immunol. (2006) 63, 410-9
39. Asgrimsson V, Gudjonsson T, Gudmundsson GH, Baldursson O. Novel effects of azithromycin on tight junction proteins in human airway epithelia. Antimicrob Agents Chemother. (2006) 50, 1805-12
40. Peter Bergman, Linda Johansson, Hong Wan, Allison Jones, Richard L. Gallo, Gudmundur H. Gudmundsson, Tomas Hökfelt, Ann-Beth Jonsson and Birgitta Agerberth. (2006) Induction of the Antimicrobial Peptide CRAMP in the Blood Brain Barrier and Meninges after Meningococcal Infection. Infection and Immunity, 74, 6982-91
41. Kai-Larsen Y, Bergsson G, Gudmundsson GH, Printz G, Jörnvall H, Marchini G, Agerberth B. (2007) Antimicrobial components of the neonatal gut affected upon colonization. Pediatr Res. 61:530-6.
42. Halldorsson S, Asgrimsson V, Axelsson I, Gudmundsson GH, Steinarsdottir M, Baldursson O, Gudjonsson T. (2007) Differentiation potential of a basal epithelial cell line established from human bronchial explant. In Vitro Cell Dev Biol Anim. 43:283-9.
43. Maier VH, Schmitt CN, Gudmundsdottir S, Gudmundsson GH. (2008) Bacterial DNA indicated as an important inducer of fish cathelicidins. Mol Immunol. 45:2352-8.
44. Termén S, Tollin M, Rodriguez E, Sveinsdóttir SH, Jóhannesson B, Cederlund A, Sjövall J, Agerberth B, Gudmundsson GH. (2008) PU.1 and bacterial metabolites regulate the human gene CAMP encoding antimicrobial peptide LL-37 in colon epithelial cells. Mol Immunol. 45:3947-55.
45. Maier VH, Dorn KV, Gudmundsdottir BK, Gudmundsson GH. (2008) Characterisation of cathelicidin gene family members in divergent fish species. Mol Immunol. 45:3723-30.
46. Steinmann J, Halldórsson S, Agerberth B, Gudmundsson GH. (2009) Phenylbutyrate induces antimicrobial peptide expression. Antimicrob Agents Chemother. 53:5127-33.
47. Halldorsson S, Gudjonsson T, Gottfredsson M, Singh PK, Gudmundsson GH, Baldursson O. (2010) Azithromycin maintains airway epithelial integrity during Pseudomonas aeruginosa infection. Am J Respir Cell Mol Biol. 42:62-8.
48. Broekman DC, Frei DM, Gylfason GA, Steinarsson A, Jörnvall H, Agerberth B, Gudmundsson GH, Maier VH. (2011) Cod cathelicidin: isolation of the mature peptide, cleavage site characterisation and developmental expression. Dev Comp Immunol. 35:296-303.
49. Sarker P, Ahmed S, Tiash S, Rekha RS, Stromberg R, Andersson J, Bergman P, Gudmundsson GH, Agerberth B, Raqib R. (2011) Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy. PLoS One. 6(6):e20637
50. Cederlund A, Gudmundsson GH, Agerberth B. (2011) Antimicrobial peptides important in innate immunity. FEBS J. 278:3942-51
51. Broekman DC, Zenz A, Gudmundsdottir BK, Lohner K, Maier VH, Gudmundsson GH. (2011) Functional characterization of codCath, the mature cathelicidin antimicrobial peptide from Atlantic cod (Gadus morhua). Peptides 32:2044-51.
52. Sigurdardottir SL, Thorleifsdottir RH, Guzman AM, Gudmundsson GH, Valdimarsson H, Johnston A. (2012) The anti-microbial peptide LL-37 modulates immune responses in the palatine tonsils where it is exclusively expressed by neutrophils and a subset of dendritic cells. Clin Immunol. 142:139-49.
53. Raqib R, Sarker P, Mily A, Alam NH, Arifuzzaman AS, Rekha RS, Andersson J, Gudmundsson GH, Cravioto A, Agerberth B. (2012) Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebocontrolled clinical trial. BMC Infect Dis. 12:111
     

Published in connection with a meeting:

1. Agerberth B., Gunne H., Odeberg J., Kogner P., Boman H.G. & Gudmundsson G.H. (1996) PR-39, a proline-rich peptide antibiotic from pig, and FALL-39, a human tentative counterpart. Vet. Immunol. Immunopathol. 54, 127-131.
2. Andersson M, Gunne H., Agerberth B., Boman A., Bergman T., Olsson B., Dagerlind Å., Wigzell H., Boman H.G. & Gudmundsson G.H. (1996) NK-lysin, structure and function of a novel effector molecule of porcine T and NK cells. Vet. Immunol. Immunopathol. 54, 123-126.
    

Thesis, Reviews and book chapters

Thesis: Gudmundur H. Gudmundsson (1992) Structure and Expression of the Cecropin Locus in the Moth Hyalophora cecropia. Ph.D., Stockholm University.

Reviews:

1) Boman H.G., Faye I., Gan R.B., Gudmundsson G.H., Lidholm D.-A., Lee J.-Y. & Xanthopoulos K.G. (1987) Insect immunity - A gene system for antibacterial proteins. Mem. Inst. Oswaldo. Cruz. Rio de Janeiro, vol 82 Intern. Symp. on insects.

2) Boman H.G., Faye I., Gudmundsson G.H., Lee J.-Y. & Lidholm D.-A., (1991) Cell-free immunity in Cecropia - A model system for antibacterial proteins. Eur. J. Biochem. 201, 23-31.

3) Gudmundsson, G.H. & Agerberth, B. (1999) Neutrophil antibacterial peptides, multifunctional effector molecules in the mammmalian immune system. Review J. Immun. Meth. 232, 45-54.

4) Agerberth, B. & Gudmundsson, G.H. Human cathelicidin antimicrobial peptide LL-37. (2003) Cytokine Reference Online (http://www.apnet.com/cytokinereference/) ed Oppenheim, J.J. and Feldman, M. Academic press.

5) Gudmundsson, G.H. & Agerberth, B. Biology and expression of the human cathelicidin LL-37 in Mammalian Antimicrobial Peptides, (2004) Cambridge University Press, ed Devine, D.A. and Hancock, R.E.W.

6) Gudmundsson, G.H. and Agerberth, B. Antimirobial peptides in human blood in Antimicrobial Peptides in Human Health and Disease, (2005) ed Gallo, R.L. Horizon Scientific Press/Caister Academic Press.

7) Gudmundsson, G.H. and Agerberth, B. Host antimicrobial defence peptides in human disease. Curr Top Microbiol Immunol. (2006) 306:67-90.

8) Bergmann P, Gudmundsson GH, Agerberth B. Läkartidningen (2008) Naturlig immunitet – första linjens försvar. 105: 2254-2259

9) Gudmundsson GH, Bergman P, Andersson J, Raqib R, Agerberth B. (2010) Battle and balance at mucosal surfaces--the story of Shigella and antimicrobial peptides. Biochem Biophys Res Commun. 2010 May 21;396(1):116-9.

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