Bo Porse

Head of Department

Key research interests
Bo Porse´s research is focused on delineating the underlying mechanisms that regulate normal and malignant hematopoiesis with particular emphasis on those governing the behaviour of normal and leukemic stem cells.

Experimental systems involve phenotyping of genetically modified mouse lines in which selected genes encoding transcription factors, epigenetic regulators and posttranscriptional regulators of gene expression can be conditionally deleted/overexpressed in normal and leukemic cells. We also invest major resources in defining leukemic hierarchies in human samples derived from patients diagnosed with Acute Myeloid Leukemia by using a combination of cell sorting, gene expression profiling and functional assays.

Major Experimental Competences: Multicolour flow cytometry, microarray-based gene expression profiling, RNA-seq, ChiP-seq, nanoCAGE-seq and Bioinformatics

Publications

2011
41. Theilgaard-Mönch KT, Boultwood J, Ferrari S, Giannopoulos K, Hernandez-Rivas JM, Kohlmann A, Morgan M, Porse BT, Tagliafico E, Zwaan CM, Wainscoat J, van den Heuvel-Eibrink M, Mills K and Bullinger L (2011) Gene expression profiling in MDS and AML: Potential and Future Avenues. Leukemia, In press (Review)

2010
40. Wu H, Santoni-Rugiu E, Ralfkjær E, Porse B, Moser C, Høiby N, Borregaard N and Cowland JB (2010) Neutrophil Gelatinase-Associated Lipocalin is protective against E. coli pneumonia. Respir Res, 11, 96-
39. Porse BT, Petersen OW and Helin K (2010) Stem cell biology and Cancer. Ugeskr Laeger, 172, 2600-2603 (Review).
38. Thoren LA, Nørgaard GA, Weischenfeldt J, Waage J, Jakobsen JS, Damgaard I, Bergström FC, Blom AM, Borup R, Bisgaard HC and Porse BT (2010) NMD is a critical regulator of liver development, function and regeneration. Plos One, 19, e11650
37. Marstrand TT, Borup R, Willer A, Borregaard N, Sandelin A, Porse BT* and Theilgaard-Mönch* (2010) A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia. Leukemia, 24, 1265-1275. Epub 2010 May 27.
36. Pasini D, Malatesta M, Jung HR, Walfridsson J, Willer A, Olsson L, Skotte J, Wutz A, Porse B, Jensen ON and Helin K (2010) Characterization of an antagonistic switch between Histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Research, 38, 4958-4969, Apr 10 (Epub ahead of print).

2009
35. Schuster MB and Porse BT (2009) C/EBP in leukemogenesis: Identity and origin of the leukemia initiating cell. Biofactors, 35, 227-231 (Review).

2008
34. Weischenfeldt J and Porse BT (2008) Bone Marrow-derived Macrophages (BMMs): Isolation and applications. Cold Spring Harb. Protoc; doi:10.1101/pdb.prot5080
33. Weischenfeldt J, Damgaard I, Bryder D, Theilgaard-Mönch K, Thoren LA, Nielsen FC, Jacobsen SE, Nerlov C and Porse BT (2008) NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements. Genes Dev., 22, 1381-1396
32. Kirstetter P, Schuster MB, Bereshchenko O, Moore S, Dvinge H, Kurz E, Theilgaard-Mönch, K, Månsson, R, Pedersen TÅ, Pabst T, Schröck E, Porse BT, Jacobsen, SEW, Bertone, P, Tenen DG and Nerlov C (2008) Modelling of C/EBP mutant acute myeloid leukaemia reveals a common expression signature of committed myeloid leukaemia initiating cells . Cancer Cell, 13, 299-310.
31. Hasemann MS, Damgaard I, Schuster MB, Theilgaard-Mönch K, Sørensen AB, Mrsic A, Krugers T, Ylstra B, Pedersen FS, Nerlov C and Porse BT (2008) A retroviral insertional mutagenesis screen in a Cebpa mutant background. Blood, 111, 4309-4321, Epub Jan 22.
30. Christoffersen C, Jauhiainen M, Moser M, Porse B, Ehnholm C, Boesl M, Dahlbäck B, Nielsen LB (2008) Effect of apolipoprotein M on HDL metabolism and atherosclerosis in LDL receptor knockout mice. J. Biol. Chem., 283, 1839-1847.

2007
29. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Mönch K, Minucci S, Porse BT, Marine J-C, Hansen KH and Helin K (2007) The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev., 21, 525-530.
28. Pedersen TÅ, Bereshchenko O, Garcia-Silva S, Ermakova O, Kurz E, Mandrup S, Porse BT and Nerlov C (2007) Distinct C/EBP amino acid motifs regulate lipogenic and gluconeogenic gene expression in vivo. EMBO J., 26, 1081-1093.

2006
27. Kirstetter P, Anderson K, Porse BT, Jacobsen SE and Nerlov C (2006) Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat Immunol, 7, 1048-1056. Epub Sep 3.
26. Schuster M and Porse BT (2006) C/EBP: A tumour suppressor in multiple tissues? BBA reviews on cancer 1766, 88-103. Epub 2006 Mar 24 (Review).
25. Theilgaard-Mönch K, Jacobsen LC, Nielsen MJ, Rasmussen T, Udby L, Gharib M, Arkwright PD, Gombart AF, Calafat J, Moestrup SK, Porse BT and Borregaard N (2006) Haptoglobin is synthesized during granulocytic differentiation, stored in secondary granules, and released by neutrophils in response to activation. Blood, 108, 353-361. Epub 2006 Mar 16.
24. Porse BT, Pedersen TÅ, Hasemann MS, Schuster MB, Kirstetter P, Luedde T, Damgaard I, Kurz E, Schjerling CK and Nerlov C (2006) The proline histidine rich CDK2/4 interaction domain of C/EBPalpha is dispensable for C/EBPalpha-mediated growth regulation in vivo. Mol. Cell. Biol., 26, 1028-1037.
23. Theilgaard-Mönch K, Porse BT and Borregaard N (2006) Systems biology of neutrophil differentiation and immune response. Curr Opin Immunol. 18, 54-60. Epub 2005 Dec 7 (Review)

2001-2005
22. Weischenfeldt J, Lykke-Andersen J and Porse BT (2005) Messenger RNA surveillance: Neutralizing Natural Nonsense. Curr Biol., 15, R559-R562 (Review).
21. Porse BT, Bryder D, Theilgaard-Mönch K, Hasemann MS, Anderson K, Damgaard I, Jacobsen SE and Nerlov C (2005) Loss of C/EBP cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage. J. Exp. Med. 202, 85-96, Epub 2005 Jun 27.
20. Theilgaard-Mönch K, Jacobsen LC, Rasmussen T, Niemann C, Udby L, Borup R, Calafat J, Porse BT and Borregaard N (2005) Highly glycosylated Alpha-1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils. J. Leuk. Biol., 78 (2), 462-470. Epub 2005 Jun 7.
19. Andersen TE, Porse BT and Kirpekar F (2004) A novel partial modification at C2501 in Escherichia coli 23S ribosomal RNA. RNA, 10, 907-913.
18. Long K and Porse BT (2003) A conserved chloramphenicol binding site at the entrance to the ribosomal peptide exit tunnel. Nucleic Acid Research, 31, 7208-7215.
17. Schuster MB and Porse BT (2003) Transgenic mice as disease models. Ugeskr Laeger, 165, 793-796. (Review).
16. Porse BT, Pedersen TÅ, Xu X., Lindberg B., Wewer UM, Friis-Hansen, L. & Nerlov C (2001) E2F repression by C/EBP is required for adipogenesis and granulopoiesis in vivo. Cell, 107, 247-258.

2000 and before
15. Rodriguez-Fonseca C, Phan H, Long, KS, Porse BT, Kirillov SV, Amils R & Garrett, RA (2000) Puromycin-rRNA interaction sites at the peptidyl transferase center. RNA. 6, 744-754.
14. Porse BT, Kirillov SV & Garrett RA (2000) Antibiotics and the Peptidyl Transferase Centre. In: The ribosome: Structure, function, antibiotics, and cellular interactions. (Garrett RA, Douthwaite SR, Liljas A, Matheson AT, Moore PB, Noller HF, eds). Washington DC: American Society for Microbiology Press. pp 441-449 (Review).
13. Porse BT, Kirillov SV, Awayez, MJ & Garrett RA (1999) Direct crosslinking of the antitumour antibiotic sparsomycin, and its derivates, to A2602 in the peptidyl transferase centre of 23S-like rRNA within ribosome-tRNA complexes. Proc. Natl. Acad. Sci., 96, 9003-9008.
12. Kirillov S, Porse BT & Garrett RA (1999) Peptidyl transferase antibiotics perturb the relative positioning of the 3’-terminal adenosine of P/P’-site-bound tRNA and 23S rRNA in the ribosome. RNA, 5, 1003-1013.
11. Porse BT & Garrett RA (1999) Ribosomal mechanics, antibiotics and GTP hydrolysis. Cell, 97, 423-426. (Review)
10. Porse BT, Kirillov SV, Awayez MJ & Garrett RA (1999) UV-induced modifications in the peptidyl transferase loop of 23S rRNA on binding of the streptogramin B antibiotic, pristinamycin IA. RNA, 5, 585-595.
9. Porse BT, Cundliffe E & Garrett RA (1999) The antibiotic micrococcin acts on protein L11 at the ribosomal GTPase centre. J. Mol. Biol., 287, 33-45.
8. Porse BT & Garrett RA (1999) Sites of Interaction of Streptogramin A and B Antibiotics in the Peptidyl Transferase Loop of 23 S rRNA and the Synergism of their Inhibitory Mechanisms. J. Mol. Biol., 286, 375-387.
7. Østergaard P., Phan H, Johansen LB, Egebjerg J, Østergaard L, Porse BT & Garrett RA (1998) Assembly of proteins and 5S rRNA to transcripts of the major structural domains of 23S rRNA. J. Mol. Biol., 284, 227-240.
6. Porse BT, Leviev I, Mankin AS & Garrett RA (1998) The antibiotic thiostrepton inhibits a functional transition within protein L11 at the ribosomal GTPase centre. J. Mol. Biol., 276, 391-404.
5. Kirillov S, Porse BT, Vester B, Woolley P & Garrett RA (1997) Movement of the 3´-end of tRNA through the peptidyl transferase centre and its inhibition by antibiotics. FEBS Lett., 406, 223-233. (Review)
4. Porse BT, Thi-Ngoc HP & Garrett RA (1996) The donor substrate site within the peptidyl transferase loop of 23 S rRNA and its putative interactions with the CCA-end of N-blocked aminoacyl-tRNA(Phe). J Mol Biol, 264, 472-483.
3. Lazaro E, Rodriguez-Fonseca C, Porse BT, Urena D, Garrett RA & Ballesta JP (1996) A sparsomycin-resistant mutant of Halobacterium salinarium lacks a modification at nucleotide U2603 in the peptidyl transferase centre of 23 S rRNA. J Mol Biol, 261, 231-238.
2. Porse BT, Rodriguez-Fonseca C, Leviev I & Garrett RA (1995) Antibiotic inhibition of the movement of tRNA substrates through a peptidyl transferase cavity. Biochem Cell Biol, 73, 887-885. (Review)
1. Porse BT & Garrett RA (1995) Mapping important nucleotides in the peptidyl transferase centre of 23 S rRNA using a random mutagenesis approach. J. Mol. Biol., 249, 1-10.