The communication of cells, tissues and organs is critical for the maintenance of the entire body homeostasis. Comprehensive deciphering of the signaling events triggered by hormones, growth factors and cytokines is essential for the understanding of the biological processes that occur in the organism. The processes that the secreted factors trigger are as distinct as differentiation and growth to apoptosis, autophagy and ageing. The major aim of our research is concentrated on the comprehensive characterization of secreted molecules by different cellular subtypes, tissues and organs that can contribute to the elucidation of the physiological state of a given organism and to the determination of the malfunction in diseased stages.
We focus on analysis of factors secreted by different types of mammalian cells and systems that can contribute to the development of complex and often incurable diseases, such as metabolic disorders and the inherited complications connected with them. We target the entire secretomes of mesenchymal cells during specific processes of differentiation and disease models using state-of-the-art quantitative proteomics, bioinformatics and complementary molecular biology approaches. In particular, our research is primarily directed at investigation of the mechanisms underlying the differentiation program of myotubes, adipocytes and osteocytes. We utilized the advantages of highly sensitive and accurate methods for quantitative proteomics, such as SILAC combined with conventional molecular biology techniques to delineate entire signaling cascades in space and time and to obtain new insights into the regulation and control of complex cellular processes during the differentiation program of mesenchymal stem cells and other cell types of mesenchymal origin. Our ultimate goal is to shed light on the mechanisms underlying major diseases and disorders and the translation of basic research to the development of improved and combinatorial therapies bringing us a step closer to the establishment of personalized medicine.
Head of research: Associate professor, PhD Irina Kratchmarova
Academic staff Vyacheslav Akimov
Major areas of interest
- Global investigation of the insulin and IGF-1 signaling pathways in fat and muscle
- Characterization of secreted factors produced by mouse and human adipocytes (adipokines) by application of quantitative mass spectrometry based proteomics (SILAC-based approach)
- Identification and functional analysis of factors secreted by human mesenchymal stem cells during the conversion to mature adipocytes
- Influence of insulin and anti-diabetic drugs on adipokine production (secretion/expression) using triple encoding SILAC
- Identification and characterization of secreted proteins from skeletal muscle cells during myogenesis using a quantitative proteomic platform combined with conventional protein, RNA expression analysis and targeted siRNA silencing approach
- Functional characterization of newly identified myokines, including growth factors, cytokines and chemokines and defining their auto-, para- and endocrine mechanism of action
- Analysis of modifications in the muscle secretome that are involved in the physiopathology of Dysferlinopathies
- Investigation of specific cross talks and interactions between fat, muscle and bone
Henningsen J, Pedersen BK, Kratchmarova I. (2011) “Quantitative analysis of the secretion of the MCP family of chemokines by muscle cells” Mol Biosyst. 2011 Feb 1;7(2):311-21.
Henningsen J, Rigbolt KT, Blagoev B, Pedersen BK, Kratchmarova I. (2010) “Dynamics of the skeletal muscle secretome during myoblast differentiation.” Mol Cell Proteomics. 2010 Nov;9(11):2482-96.
Hammond DE, Hyde R, Kratchmarova I, Beynon RJ, Blagoev B, Clague MJ. (2010) Quantitative Analysis of HGF and EGF-Dependent Phosphotyrosine Signaling Networks. J Proteome Res, 9(5):2734-42
Deribe YL, Wild P, Chandrashaker A, Curak J, Schmidt MH, Kalaidzidis Y, Milutinovic N, Kratchmarova I, Buerkle L, Fetchko MJ, Schmidt P, Kittanakom S, Brown KR, Jurisica I, Blagoev B, Zerial M, Stagljar I, Dikic I. (2009) Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Sci Signal.;2(102):ra84.
Prokhorova TA, Rigbolt KT, Johansen PT, Henningsen J, Kratchmarova I, Kassem M, Blagoev B.(2009) “Stable isotope labeling by amino acids in cell culture (SILAC) and quantitative comparison of the membrane proteomes of self-renewing and differentiating human embryonic stem cells.” Mol Cell Proteomics. May;8(5):959-70
Krüger M, Kratchmarova I, Blagoev B, Tseng YH, Kahn CR, Mann M. (2008) “Dissection of the insulin signaling pathway via quantitative phosphoproteomics” Proc Natl Acad Sci U S A 105(7):2451-6.
Hacker H, Redecke V, Blagoev B, Kratchmarova I, Hsu LC, Wang GG, Kamps MP, Raz E, Wagner H, Hacker G, Mann M, Karin M. (2006) “Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6” Nature, 439 (7073): 204-7.
Kratchmarova I, Blagoev B, Haack-Sorensen M, Kassem M, Mann M. (2005) “Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation” Science, 308 (5727): 1472-7.
Blagoev B, Ong SE, Kratchmarova I, Mann M. (2004) “Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics” Nat Biotechnol, 22 (9): 1139-45
Ong SE, Kratchmarova I, Mann M. (2003) “Properties of 13C-substituted arginine in stable isotope labeling by amino acids in cell culture (SILAC)” J Proteome Res, 2 (2): 173-81]
Blagoev B, Kratchmarova I, Ong SE, Nielsen M, Foster LJ, Mann M. (2003) “A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signalling” Nat Biotechnol, 21 (3): 315-18
Kratchmarova I, Kalume DE, Blagoev B, Scherer PE, Podtelejnikov AV, Molina H, Bickel PE, Andersen JS, Fernandez MM, Bunkenborg J, Roepstorff P, Kristiansen K, Lodish HF, Mann M, Pandey A. (2002) “A Proteomic Approach for Identification of Secreted Proteins During the Differentiation of 3T3-L1 Preadipocytes to Adipocytes” Mol Cell Proteomics, 1 (3): 213-22
Blagoev B, Kratchmarova I, Nielsen MM, Fernandez MM, Voldby J, Andersen JS, Kristiansen K, Pandey A, Mann M. (2002) “Inhibition of adipocyte differentiation by Resistin like molecule alpha (RELM alpha): Biochemical characterization of its oligomeric nature”. J Biol Chem, 277 (44): 42011-6.
Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M. (2002) “Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics”. Mol Cell Proteomics, 1 (5): 376-86.
Kratchmarova I., Sosinowski T., Weiss A., Witter K., Vincenz C., Pandey A. (2001) “Characterization of promoter region and genomic structure of the murine and human genes encoding Src like adapter protein (SLAP)”. Gene, 262: 267-73
Gruhler A, Kratchmarova I. (2008) “Stable Isotope Labeling by Amino acids in Cell culture (SILAC)” Methods in Molecular Biology, series Functional Proteomics Methods and Protocols. 484: 101-111
Blagoev B, Kratchmarova I, Olsen JV, Mann M#. (2008) Temporal dynamics of EGF receptor signaling by quantitative proteomics. EGFR Signaling Networks in Cancer Therapy. Ed. John D. Haley & William J. Gullick. The Humana Press Inc.
Minet A, Kristiansen K, Kratchmarova I. (2007) “Quantitative proteomics for the analysis of adipocyte development and function.” Taylor & Francis Group, LLC: Genetics in Obesity
Ong SE, Blagoev B, Kratchmarova I, Foster LJ, Andersen JS, Mann M. (2005) “Stable isotope labelling with amino acids in cell culture for quantitative proteomics” Cell Biology – A Laboratory Handbook,3rd Edition. Ed. Julio Celis. Academic Pres.