Marko Hyvönen

Short scientific bio

Marko studied biochemistry, chemistry and physiology at the University of Helsinki in Finland, graduating in 1991. After a couple of years in the group of Leevi Kääriäinen at the Institute of Biochemistry at the University of Helsinki, he secured a PhD studentship at EMBL in Heidelberg, Germany.

His PhD project in the group of late Matti Saraste was focused on understanding how newly discovered pleckstrin homology (PH) and WW domains function, and was awarded a PhD at the end of 1997. He was awarded Komppa’s prize for the best PhD thesis in the field of chemistry that year in Finland.

In January 1998 Marko joined the Department of Biochemistry in Cambridge as an EMBO and HFSPO-funded postdoctoral fellow in the group of Tom Blundell. He started the still ongoing work on activins and TGF-β family growth factors at that time.

He was awarded a BBSRC David Phillips Fellowship to study the regulation of activin A signalling by extracellular proteins in 2000, and established his independent research programme in Jan 2001.

Around 2006 Marko and his group joined forces with Profs Chris Abell, Tom Blundell , David Spring and Ashok Venkitaraman to develop small molecule inhibitors of protein-protein interactions and other regulatory sites using fragment-based drug discovery (FBDD) methods, targeting RAD51, Aurora A and CK2alpha.

He is collaborating with Caroline Hill at the Crick, Petra Knaus at Frei Unviersity of Berlin, Morten Grøtli at University of Copenhagen and Andrea Balan at the University of São Paulo, among others.

In 2008 Marko was appointed as a University Lecturer at the Department of Biochemistry and is currently a Professor in Protein Biochemistry.

In 2016, together with Dr Catherine Elton, Marko founded in 2016 a spin-out company Qkine Ltd for the development of next generation growth factors for stem cell research and regenerative medicine.

Departmental website:

Twitter: @HyvonenGroup

LinkedIn: Marko Hyvönen

ORCiD: 0000-0001-8683-4070


Published articles (updated Nov 2021- search “Hyvonen-M” in PubMed for the latest ones):

L. H. Lindenburg, T. Pantelejevs, F. Gielen, P. Zuazua-Villar, M. Butz, E. Rees, C. F. Kaminski, J. A. Downs, M. Hyvönen, F. Hollfelder. Improved RAD51 binders through motif shuffling based on the modularity of BRC repeats. Proc Natl Acad Sci U S A, 118:e2017708118. Ratcliff, R. X. Zhou, L. Jermutus, M. Hyvönen. The role of pro-domains in human growth factors and cytokines. Biochem Soc Trans (2021) BST20200663.
N. Kostopoulou, S. Bellou, E. Bagli, M. Markou, E. Kostaras, M. Hyvönen, Y. Kalaidzidis, A. Papadopoulos, V. Chalmantzi, A. Kyrkou, E. Panopoulou,T. Fotsis, C. Murphy. Embryonic stem cells are devoid of macropinocytosis, a trafficking pathway for activin A in differentiated cells. J. Cell. Sci. jcs.246892, 2021.
A. Ramachandran, M. Mehić, L. Wasim, D. Malinova, I. Gori, B. K. Blaszczyk, D. M. Carvalho, E. M. Shore, C. Jones, M. Hyvönen, P. Tolar, C. S. Hill. Pathogenic ACVR1R206H activation by Activin A-induced receptor clustering and autophosphorylation. EMBO J, e106317, 2021
E. L. Atkinson, J. Iegre, P. D. Brear, E. A. Zhabina, M. Hyvönen, D. R. Spring. Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study. Molecules. 26:1977, 2021.
D. E. Scott, N. J. Francis-Newton, M. E. Marsh, A. G. Coyne, G. Fischer, T. Moschetti, A. R. Bayly, T. D. Sharpe, K. T. Haas, L. Barber, C. R. Valenzano, R. Srinivasan, D. J. Huggins, M. Lee, A. Emery, B. Hardwick, M. Ehebauer, C. Dagostin, A. Esposito, L. Pellegrini, T. Perrior, G. McKenzie, T. L. Blundell, M. Hyvönen, J. Skidmore, A. R. Venkitaraman, C. Abell. A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death. Cell Chemical Biology, 28: 1–13, 2020. PMCID: PMC821902
A. Papadopoulos, V. Chalmantzi, O. Mikhaylichenko, M. Hyvönen, D. Stellas, A. Kanhere, J. Heath, D. L. Cunningham, T. Fotsis, C. Murphy. Combined transcriptomic and phosphoproteomic analysis of BMP4 signaling in human embryonic stem cells. Stem Cell Research 50:102133, 2021.
P. D. Brear, D. Ball, K. Stott, S. D’Arcy and M. Hyvönen. Proposed allosteric inhibitors bind to the ATP site of CK2α. J Med Chem: 63:12786–12798, 2020.
S. L. Kidd, E. Fowler, T. Reinhardt, T. Compton, N. Mateu, .H. Newman, D. Bellini, R. Talon, J. McLoughlin, T. Krojer, A. Aimon, A. Bradley, M. Fairhead, P. Brear, L. Díaz-Sáez, K. McAuley, H. Sore, A. Madin, D. H O’Donovan, K. Huber, M. Hyvönen, F. von Delft, C. G. Dowson and D. R. Spring. Demonstration of the utility of DOS-derived fragment libraries for rapid hit derivatisation in a multidirectional fashion. Chemical Science, 11: 10792-10801, 2020.
T.Sonoyama, L. K. J. Stadler, M. Zhu, J. M. Keogh, E. Henning, F. Hisama, P. Kirwan, M. Jura, B. K. Blaszczyk, D. C. DeWitt, B. Brouwers, M. Hyvönen, I. Barroso, F. T. Merkle, S. M. Appleyard, G. A. Wayman, I. S. Farooqi. Human BDNF/TrkB Variants Impair Hippocampal Synaptogenesis and Associate With Neurobehavioural Abnormalities. Scientific Reports,10:9028, 2020.
A. V. Strizhak, O. Babii, S. Afonin, I Bakanovich, T. Pantelejevs, W. Xu, E. Fowler, R. Eapen, K. Sharma, M. O. Platonov, V. V. Hurmach, L. Itzhaki, M Hyvönen, A. S. Ulrich, D. R. Spring, I. V. Komarov. Diarylethene moiety as an enthalpy-entropy switch: photoisomerizable stapled peptides for modulating p53/MDM2 interaction. Org Biomol Chem, 18: 5359-536, 2020.
F. Negrini, K. O’Grady, M. Hyvönen, K. M. Folta, E. Baraldi. Genomic structure and transcript analysis of the Rapid Alkalinization Factor (RALF) gene family during host-pathogen crosstalk in Fragaria vesca and Fragaria x ananassa strawberry, PLoS One, in press, 2020
E-R. Xu, A. Lafaita, A. Bateman, M. Hyvönen. Thrombospondin module 1 domain (TSP1) of the matricellular protein CCN3 shows an atypical disulfide pattern and incomplete CWR layers. Acta Cryst. D, D76:124-134, 2020.
P. Sharma, R. Mahen, M. Rossmann, J. E. Stokes, B. Hardwick, D. J. Huggins, A. Emery, D. L. Kunciw, M. Hyvönen, D. R. Spring, G. J. McKenzie, A. R. Venkitaraman. A cryptic hydrophobic pocket in the polo-box domain of the polo-like kinase PLK1 regulates substrate recognition and mitotic chromosome segregation, Scientific Reports, 9:15930, 2019. PMCID: PMC6828814
K. Sharma, A. V. Strizhak, E. Fowler, X. Wang, W. Xu, C. Hatt Jensen, Y. Wu, H. F. Sore, Y. H. Lau, M. Hyvönen, L. S. Itzhaki, D. R. Spring. Water-soluble, stable and azide-reactive strained dialkynes for biocompatible double strain-promoted click chemistry. Organic and Biomolecular Chemistry, 2019, 17:8014-8018.
M. Urbischek, H. Rannikmae, T. Foets, K. Ravn, M. Hyvönen and M. de la Roche. Organoid culture media formulated with growth factors of defined cellular activity. Scientific Reports 6193, 2019. PMCID: PMC6470207
J. Iegre, P. Brear, D. J. Baker, Y. S. Tan, E. L. Atkinson, H. F. Sore, D. H. O’ Donovan, C. S. Verma, M. Hyvönen and D. R. Spring. Efficient development of stable and highly functionalised peptides targeting the CK2α/CK2β protein–protein interaction. Chemical Science 10:5056-5063, 2019. PMCID:PMC6530537
B. van Loo , C. D. Bayer, G. Fischer, S. Jonas, E. Valkov, M. F. Mohamed, A. Vorobieva, C. Dutruel, M. Hyvönen, and F. Hollfelder. Balancing Specificity and Promiscuity in Enzyme Evolution: Multidimensional Activity Transitions in the Alkaline Phosphatase Superfamily. Journal of American Chemical Society 141:370-387, 2019.
C. M. Miton, S. Jonas, G. Fischer, F. Duarte, M. F. Mohamed, B. van Loo, B. Kintses, S. C. L. Kamerlin, N. Tokuriki, M. Hyvönen, and F. Hollfelder. Evolutionary repurposing of a sulfatase: A new Michaelis complex leads to efficient transition state charge offset. Proceedings of the National Academy of Sciences of the USA 115:E7293-E7302, 2018.
P. Brear, A. North, J. Iegre, K. Hadje Georgiou, A. Lubin, L. Carro, W. Green, H. F. Sore, M. Hyvönen, D, R.Spring. Novel non-ATP competitive small molecules targeting the CK2 α/β interface. Bioorganic & Medicinal Chemistry, 2018, 26:3016-3020.
B. van Loo, M. Schober, E. Valkov, M. Heberlein, E. Bornberg-Bauer, K. Faber, M. Hyvönen, F. Hollfelder. Structural and Mechanistic Analysis of the Choline Sulfatase from Sinorhizobium melliloti: A Class I Sulfatase Specific for an Alkyl Sulfate Ester. Journal of Molecular Biology 430: 1004-1023, 2018.
S. J. Walsh, S. Omarjee, W. R. J. D. Galloway, T. T.-L. Kwan, H. F. Sore, J. S. Parker, M. Hyvönen, J. S. Carroll and D. R. Spring. A general approach for the site-selective modification of native proteins, enabling the generation of stable and functional antibody–drug conjugates. Chemical Science 10: 694-700, 2019.
J. Iegre, P. Brear, C. De Fusco, M. Yoshida, S. L. Mitchell, M. Rossmann, L. Carro Santos, H. F. Sore, M. Hyvӧnen and D. R. Spring. Second-generation CK2α inhibitors targeting the αD pocket. Chemical Science, 2018, 9:3041-3049. PMCID:PMC5916021
T. Cotton, G. Fischer, X. Wang, J. McCoy, M. Czepnik, T. B. Thompson, M. Hyvӧnen. Structure of the human pro-myostatin precursor and determinants of growth factor latency. EMBO Journal 37:367-383, 2018. PMCID:PMC5793801
R. G. Walker, J. C. McCoy, M. Czepnik, M. J. Mills, A. Hagg, K. L. Walton, T. Cotton, M. Hyvönen, R. T. Lee, P. Gregorevic, C. A. Harrison, T. B. Thompson. Molecular characterization of latent GDF8 reveals mechanisms of activation. PNAS 115:E866-E875, 2018.
D. J. Cole, M. Janecek, J. E. Stokes, M. Rossmann, J. C. Faver, G. J. McKenzie, A. R. Venkitaraman, M. Hyvönen, D. R. Spring, D. J. Huggins, and W. L. Jorgensen Computationally-Guided Optimization of Small-Molecule Inhibitors of the Aurora A Kinase – TPX2 Protein-Protein Interaction. Chemical Communications 53, 9372-9375, 2018.
E.-R. Xu, E. E. Blythe, G. Fischer, M. Hyvönen. Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2. Journal of Biological Chemistry 292:12516–12527, 2017.
C. De Fusco, P. Brear, J. Iegre, K. H. Georgiou, H. F. Sore, M. Hyvönen, D. R. Spring. A fragment-based approach leading to the discovery of a novel binding site and the selective CK2 inhibitor CAM4066. Bioorganic and Medicinal Chemistry 25:3471-3482, 2017. PMCID:PMC5587527
M. Rossmann, S. Greive, T. Moschetti, M. Dinan, M. Hyvönen. Development of a Multipurpose Scaffold for the Display of Peptide Loops. Proteins: Engineering, Design and Selection 24:1-12, 2017. PMCID:PMC5897841
M. Rangel Pereira, T. Carvalho Maester, G. F. Mercaldi, E. G. de Macedo Lemos, M. Hyvönen, A. Balan. From a metagenomic source to a high-resolution structure of a novel alkaline esterase. Applied Microbiology and Biotechnology 101:4935-4949, 2017.
W. Xu, Y. H. Lau, G. Fischer, Y. S. Tan, A. Chattopadhyay, M. de la Roche, M. Hyvönen, C. S. Verma, D. R. Spring, and L. S. Itzhaki. Macrocyclized extended peptides: Inhibiting the substrate-recognition domain of tankyrase. Journal of the American Chemical Society 139:2245-2256, 2017.
F. Gielen, M. Butz, E. J. Rees, M. Erdelyi, T. Moschetti, M. Hyvönen, J. B. Edel, C. F. Kaminski, F. Hollfelder. Quantitative affinity determination by fluorescence anisotropy measurements of individual nanoliter droplets. Analytical Chemistry 89:1092-1101, 2016.
T. Moschetti, T. Sharpe, G. Fischer, M. E. Marsh, H. Ng, M. Morgan, D. Scott, T. L. Blundell, A. R.Venkitaraman, J. Skidmore, C. Abell, M. Hyvönen. Engineering archeal surrogate systems for the development of protein-protein interaction inhibitors against human RAD51. Journal of Molecular Biology, 428:4589-4607, 2016. PMCID:PMC5117717
P. Brear, C. De Fusco, K. Hadje Georgiou, N. J. Francis-Newton, C. J. Stubbs, H. F. Sore, A. R. Venkitaraman, C. Abell, D. R. Spring, M. Hyvönen. Specific inhibition of CK2α from an anchor outside the active site. Chemical Science 7: 6839-6845, 2016. PMCID:PMC5355960
X. Wang, G. Fischer and M. Hyvönen. Structure and activation of pro-activin A. Nature Communications, 7:12052, 2016. PMCID: PMC4932183
M. Janeček, M. Rossmann , P. Sharma, A. Emery, D.J. Huggins, S.R. Stockwell, J.E. Stokes, Y.S. Tan, E.G. Almeida, B. Hardwick, A.J. Narvaez, M. Hyvönen, D.R. Spring, G.J. McKenzie, A.R. Venkitaraman. Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2. Scientific Reports. 6:28528, 2016. PMCID:PMC4919790
M. Kasbekar, G. Fischer, B.T. Mott, A. Yasgar, M. Hyvönen, H.I. Boshoff, C. Abell, C.E. Barry 3rd, C.J. Thomas. Selective small molecule inhibitor of the Mycobacterium tuberculosis fumarate hydratase reveals an allosteric regulatory site. Proceedings of the National Academy of Sciences of the USA 113:7503-7508, 2016.
M. Marsh, M.T. Ehebauer, D. Scott, A.R. Venkitaraman, C. Abell, T.L. Blundell, M. Hyvönen. ATP-half site in RAD51 and RadA bind nucleotides. FEBS OpenBio 6:372–385, 2016. PMCID:PMC4856416
D. Scott, M. Marsh, T.L. Blundell, C. Abell and M. Hyvönen. Structure Activity Relationship of the Peptide Binding Motif Mediating the RAD51:BRCA2 Protein-Protein Interaction. FEBS Letters, 590: 1094–1102, 2016. PMCID:PMC4855620
M. Kišonaitė, X. Wang and M. Hyvönen. Structure of Gremlin-1 and analysis of its interaction with BMP-2. Biochemical Journal, 473:1593-1604, 2016.
P.-Y. Colin, B. Kintses, F. Gielen, C. M. Miton, G. Fischer, M. F. Mohamed, M. Hyvönen, D. P. Morgavi, D. B. Janssen, F. Hollfelder. Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics. Nature Communications, 6:10008, 2015.
G. Fischer, M. Rossmann, M. Hyvönen. Alternative Modulation of Protein-Protein Interactions by Small Molecules. Current Opinion in Biotechnology, 35:78-85, 2015
D.E. Scott, A. G. Coyne, T. L. Blundell, A. Venkitaraman, C. Abell, M. Hyvönen, Small molecule inhibitors targeting protein-protein interaction in the RAD51 family of recombinases, ChemMedChem, 10: 296–303, 2014 PMCID:PMC4506530
Y. H. Lau, P. de Andrade, S.-T. Quah, M. Rossmann, L. Laraia, N. Sköld, T. J. Sum, P. J. E. Rowling, T. L. Joseph, C. Verma, M.Hyvönen, L. S. Itzhaki, A. R. Venkitaraman, C. J. Brown, D. P. Lane, D. R. Spring. Functionalised staple linkages for modulating the cellular activity of stapled peptides. Chemical Science 5:18040-1809, 2014.
D. E. Scott, M. T. Ehebauer, T. Pukala, M. Marsh, T. L. Blundell, A. R. Venkitaraman, C. Abell, M. Hyvönen. Using a Fragment‐Based Approach To Target Protein–Protein Interactions. ChemBioChem 14:332-42, 2014. PMCID:PMC359497
Sharma, F. Meyer, M.Hyvönen, S. M. Best, R. E. Cameron, N. Rushton. Osteoinduction by combining bone morphogenetic protein (BMP)-2 with a bioactive novel nanocomposite. Bone and Joint Research, 2012, 1:145-51.
E. Valkov, T. Sharpe, M. Marsh, S. Greive and M. Hyvönen. Targeting protein-protein interactions and fragment-based drug discovery. in Topics in Current Chemistry: “Fragment-based drig discovery and X-ray crystallography” ed. T. Davies and M. Hyvönen, 2011,
P Sledź, C. J. Stubbs, S. Lang, Y. Q. Yang, G. J. McKenzie, A. R. Venkitaraman, M. Hyvönen, C Abell. From crystal packing to molecular recognition: prediction and discovery of a binding site on the surface of polo-like kinase 1. Angewante Chemie International Edition, 50:4003-6, 2011, PMCID: PMC3555362
B. van Loo, S. Jonas, A. C. Babtie, A. Benjdia, O. Berteau, M. Hyvönen, and F. Hollfelder. An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily. Proceedings of the National Academy of Sciences of the USA, 107:2740-5, 2010.
Hagemann, X. Xu, O. Nentwich, M. Hyvönen, K. Dingwell and J. C. Smith. Rab5-mediated endocytosis of activin is not required for gene activation or long-range signalling in Xenopus. Development, 136:2803-13, 2009
H. Ludlow, D. J. Phillips, M. Myers, R. I. McLachlan, D. M. de Kretser, C. A. Allan, R. A. Anderson, N. P. Groome, M. Hyvönen, W. C. Duncan and S. Muttukrishna. A new ‘total’ activin B ELISA: development and validation for human samples. Clinical Endocrinology. 71:867-73, 2009
S. Jonas, B. van Loo, M. Hyvönen, F. Hollfelder. A new member of the alkaline phosphatase superfamily with a formylglycine nucleophile: structural and kinetic characterisation of a phosphonate monoester hydrolase/phosphodiesterase from Rhizobium leguminosarum. Journal of Molecular Biology, 384:120-36, 2008
H. Ludlow, S. Muttukrishna, M. Hyvönen , N.P. Groome. Development of a new antibody to the human inhibin/activin betaB subunit and its application to improved inhibin B ELISAs. Journal of Immunological Methods, 329:102-111, 2008.
A.E. Harrington, S.A. Morris-Triggs, B.T. Ruotolo, C.V. Robinson, S. Ohnuma and M. Hyvönen.. Structural basis for the inhibition of activin signalling by follistatin. EMBO Journal, 25:1035-1045, 2006.
M. Hyvönen. CHRD, a novel domain in the bone morphogenetic protein inhibitor chordin, is also found in microbial proteins. Trends in Biochemical Sciences, 28: 470–473, 2003.
P. D. Ellis, J. C. Metcalf, M. Hyvönen, and P. R. Kemp. Adhesion of endothelial cells to nov is mediated by integrins v3 and 51. Journal of Vascular Research, 40:234–243, 2003.
C. A. Innis and M. Hyvönen. Crystal structures of the heparan sulfate-binding domain of follistatin. Insights into ligand binding. Journal of Biological Chemistry, 278:39969–39977, 2003.
M. Hyvönen, J. Begun, and T. Blundell. Protein-protein interactions in eukaryotic signal transduction. In C. Kleanthous, editor, Protein-Protein Recognition, Frontiers in Molecular Biology, pages 189–227. Oxford University Press, 2000.
E. Baraldi, K. Djinovic-Carugo, M. Hyvönen, P. Lo Surdo, A. M. Riley, B. V. L. Potter, R. O’Brien, J. E. Ladbury, and M. Saraste. Structure of the PH domain from Bruton’s tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate. Structure, 7:449–460, 1999.
M. Hyvönen and M. Saraste. Expression of cDNAs in Escherichia coli using T7 promoter. In J. E. Celis, editor, Cell Biology – A laboratory manual, volume 4, pages 255–261. Academic Press, 2nd edition, 1997a.
M. Hyvönen and M. Saraste. Structure of PH domain and btk motif from Bruton’s tyrosine kinase: molecular explanations for the X-linked agammaglobulinemia. EMBO Journal, 16:3396–3404, 1997b.
M. Hyvönen. Structure and function of PH and WW domains. PhD thesis, University of Helsinki, Department of Biochemistry, 1997.
J. Macias, M. Hyvönen, E. Baraldi, J. Schultz, M. Sudol, M. Saraste, and H. Oschkinat. Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide. Nature, 382:646–649, 1996.
J. Peränen, M. Rikkonen, M. Hyvönen, and L. Kääriäinen. T7 vectors with modified T7lac promoter for expression of proteins in Escherichia coli. Analytical Biochemistry, 236:371–373, 1996.
J. Peränen, P. Laakkonen, M. Hyvönen, and L. Kääriäinen. The alphavirus replicase protein nsP1 is membrane-associated and has affinity to endocytic organelles. Virology, 208:610–620, 1995.
M. Hyvönen, M. J. Macias, M. Nilges, H. Oschkinat, M. Saraste, and M. Wilmanns. Structure of the binding site for inositol phosphates in a PH domain. EMBO Journal, 14:4676–4685, 1995.
M. Saraste and M. Hyvönen. Pleckstrin homology domains: a fact file. Current Opinion in Structural Biology, 5:403–408, 1995.
G. Trave, A. Pastore, M. Hyvönen, and M. Saraste. The C-terminal domain of -spectrin is structurally related to calmodulin. European Journal of Biochemistry, 227:35–42, 1995.
T.J. Gibson, M. Hyvönen, A. Musacchio, M. Saraste, and E. Birney. PH domain: the first anniversary.Trends in Biochemical Sciences, 19:349–353, 1994.
P. Laakkonen, M. Hyvönen, J. Peränen, and L. Kääriäinen. Expression of Semliki forest virus nsP1-specific methyltransferase in insect cells and in Escherichia coli. Journal of Virology, 68:7418–7425, 1994.