Reproductive Omics Technologies

Main research topics

Laboratory Head: Professor Krassimira Olegova Todorova, PhD, DSc

Main Research Topics

Main Goal of the newly established Laboratory:

Research of the global changes at genome, transcriptome and proteome level implicated in the biological processes in normal and pathological conditions in reproductive system and related to reproduction and sexual development organs

 

Laboratory Activities:

1. Study of epigenetic regulation in reproductive and oncological phenomena.

2. Genomic and transcriptomic studies – nanopore-based 3rd generation sequencing, bioinformatics analysis of NGS data and deep sequencing library preparation.

3. Molecular modelling and molecular dynamics of ligand-receptor interactions implicated in reproduction, immunomodulation and oncology and their experimental validation.

4. Methods of exogenous and genomic expression of molecules important in embryogenesis, reproductive Immunology and oncogenesis.

5. Biomarkers – development of new methods for detection of fusion phenomena and validation of markers with diagnostic application

 

Lab Photos:

 

 

 

 

 

  • Scientific achievements

    • We have developed an experimental flow for synthetic gene design, allowing for direct cloning and eukaryote expression of very short peptides. This method was employed for the direct expression of PreImplantationFactorTM, owned by and in collaboration with BioIncept LLC (NJ, USA).
    • We have developed a method and also a diagnostic kit for the detection of natively folded protein products encoded by fusion genes like TMPRSS2:ERG with prognostic significance in prostate cancer. Patent pending. Application filed in National Patent Office, 2014.
    • We have developed a method combining high resolution confocal microscopy with 3D image processing and analysis, and Principal Component Analysis to identify the effects of specific innate immunity ligands (LPS, ie-DAP) on downstream interaction between autophagy marker LC3 and inflammasome molecule NALP3. Published in Nat Sci Rep, 2016.
    • Research Projects

      Assoc. Prof. Krassimira Todorova, PhD, DSc

      Current Research Topics:

      Prostate Cancerogenesis. Role of specific micro-RNAs in the epigenetic and transcriptional regulation of prostate cancer metastasis. Perturbation of Regulatory Gene network of miR-204 and miR-15 and transcriptional factors cMYB, RUNX2 and ETS1 in prostate cancer metastasis. Another tightly related trend of research is focused on the regulation of expression and the modes of action of prostate-specific fusion oncoproteins with regulatory function and poor prognosis association such as TMPRSS2:ERG.

      Funding:

      2011 – 2015 Project Leader, funded by National Science Fund, Bulgarian Ministry of Education and Science: Young Scientists Project Competition – “Gene regulatory networks involving miRNA, transcription factors and onco-fusion proteins in Prostate Cancerogenesis with diagnostic and therapeutic significance”

      Patents:
      1. Soren Hayrabedyan, Krassimira Todorova. Method and kit for detection of cancer fusion protein. Filled National Patent Office 2014. Currently pending.

       

       

      Assoc. Prof. Soren Hayrabedyan, MD, PhD

       

      Current Research Topics:

      Role of innate immune receptors of the NOD family and inflammasomes (NALP3) in Sertoli cell biology and immunology, implications on male fertility. Epigenetic regulation of innate immunity receptors.

      PreImplantationFactorTM (PIF) synthetic transgene design and direct eukaryote expression. PIF ligand-receptor interaction with Kv1.3 and IDE

      • Scientific publications

        Full list of research papers could be found at staff ResearchGate profies here:

        Assoc. Prof. Krassimira Todorova, DSc ,

        Assof. Prof.Soren Hayrabedyan, MD, PhD ,

        Assoc. Prof. Diana Zasheva .

         

        Patents

        1. Soren Hayrabedyan, Krassimira Todorova. Method and kit for detection of cancer fusion protein. Filled National Patent Office 2014. Currently pending.

        Books

        Book Chapters

        1. K. Todorova, S. Hayrabedyan: The stem cell paradigm and its application to prostate cancer- an old and yet still young idea. Handbook of Prostate Cancer Cell Research: Growth, Signalling and Survival, Edited by Alan T. Meridith, 01/2009: chapter The stem cell paradigm and its application to prostate cancer- an old and yet still young idea: pages 127-176; Nova Science Publishers., ISBN: 978-1-61728-435-9

        Journal Publications

        1. Soren Hayrabedyan, Krassimira Todorova, Asma Jabeen, Gergana Metodieva, Stavri Toshkov, Metodi V Metodiev, Milcho Mincheff, Nelson Fernández: Sertoli cells have a functional NALP3 inflammasome that can modulate autophagy and cytokine production. Scientific Reports 02/2016; 6(18896):1-17. DOI:10.1038/srep18896
        2. Yung Chih Chen, Jennifer Rivera, Melissa Fitzgerald, Christian Hausding, Ya-Lan Ying, Xiaowei Wang, Krassimira Todorova, Soren Hayrabedyan, Eytan R Barnea, Karlheinz Peter: PreImplantation factor prevents atherosclerosis via its immunomodulatory effects without affecting serum lipids. Thrombosis and Haemostasis 02/2016; 115(5). DOI:10.1160/TH15-08-0640
        3. Eytan R. Barnea, Soren Hayrabedyan, Krassimira Todorova, Osnat Almogi-Hazan, Reuven Or, Joy Guingab, James McElhinney, Nelson Fernandez, Timothy Barder: PreImplantation factor (PIF*) regulates systemic immunity and targets protective regulatory and cytoskeleton proteins. Immunobiology 02/2016;  DOI:10.1016/j.imbio.2016.02.004
        4. Soren B Hayrabedyan, Diana Y Zasheva, Krassimira O Todorova: NLRs Challenge Impacts Tight Junction Claudins In Sertoli Cells. Folia medica 10/2015; 57(1):43-48. DOI:10.1515/folmed-2015-0018
        5. Krassimira Todorova, soren hayrabedyan: Mir-15A Reconstitution in Prostate Cancer Cell Line Suppresses Cancer Progression Through Down Regulation of MYB and Androgen Receptor Upregulation. Acta Medica Bulgarica 05/2015; 42(1):18-22. DOI:10.1515/amb-2015-0003
        6. Soren Hayrabedyan, Krassimira Todorova: Nalp Signalling is Required in Sertoli Cells for Tight-Junction Protein Interaction. Acta Medica Bulgarica 05/2015; 42(1):12-17. DOI:10.1515/amb-2015-0002
        7. Eytan R. Barnea, David Kirk, Krassimira Todorova, James McElhinney, Soren Hayrabedyan, Nelson Fernández: PIF Direct Immune Regulation: Blocks Mitogen-Activated PBMCs Proliferation, Promotes TH2/TH1 Bias, independent of Ca2+. Immunobiology 01/2015; 220(7). DOI:10.1016/j.imbio.2015.01.010
        8. Krassimira Todorova, Metodi V Metodiev, Gergana Metodieva, Diana Zasheva, Milcho Mincheff, Soren Hayrabedyan: miR-204 is Dysregulated in Metastatic Prostate Cancer In Vitro. Molecular Carcinogenesis 01/2015; 55(2). DOI:10.1002/mc.22263
        9. E.R. Barnea, D.M. Lubman, Y.-H. Liu, V. Absalon-Medina, S. Hayrabedyan: Erratum: Insight into PreImplantation Factor (PIF) mechanism for embryo protection and development: Target oxidative stress and protein misfolding (PDI and HSP) through essential RIPK binding site (PLoS ONE (2014) 9:7 (e100263) DOI:10.1371/journal.pone.0100263). PLoS ONE 11/2014; 9(11). DOI:10.1371/journal.pone.0113886
        10. Krassimira Todorova, Diana Zasheva, Kristiyan Kanev, Soren Hayrabedyan: miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model. 10/2014; 2014(840906). DOI:10.1155/2014/840906
        11. Eytan R Barnea, David M Lubman, Yan-Hui Liu, Victor Absalon-Medina, Soren Hayrabedyan, Krassimira Todorova, Robert O Gilbert, Joy Guingab, Timothy J Barder: Insight into PreImplantation Factor (PIF*) Mechanism for Embryo Protection and Development: Target Oxidative Stress and Protein Misfolding (PDI and HSP) through Essential RIPK Binding Site. PLoS ONE 07/2014; 9(7):e100263. DOI:10.1371/journal.pone.0100263
        12. K. Todorova, Diana Zasheva, Soren Hayrabedyan: Innate immunity challenge differently modulates inflammatory and apoptosis regulation in lymph node and bone marrow metastatic cell line models, favouring higher metastatic phenotype. Comptes rendus de l’Académie bulgare des sciences: sciences mathématiques et naturelles 01/2014; 67(11):1575-1582.
        13. Asma Jabeen, José Maria Miranda-Sayago, Boguslaw Obara, Patrick Simon Spencer, Gill Barbara Dealtry, Soren Hayrabedyan, Valerie Shaikly, Pierre Philippe Laissue, Nelson Fernández: Quantified Colocalization Reveals Heterotypic Histocompatibility Class I Antigen Associations on Trophoblast Cell Membranes: Relevance for Human Pregnancy. Biology of Reproduction 09/2013; 89(4). DOI:10.1095/biolreprod.113.111963
        14. Nelly Manolova, Soren Hayrabedyan, Krassimira Todorova, Diana Zasheva, Milena Mourjeva, Stanimir Kyurkchiev, Maria Stamenova: Endometriosis Peritoneal Fluid Factors Involved in the Alteration of Decidualization Process. 08/2013; 27(4-4):3982-3986. DOI:10.5504/BBEQ.2013.0032
        15. Soren Hayrabedyan, Krassimira Todorova, Diana Zasheva, Daniela Moyankova, Desislava Georgieva, Jordana Todorova, Dimitar Djilianov: Haberlea rhodopensis has potential as a new drug source based on its broad biological modalities. 02/2013; 27(1-1):3553-3560. DOI:10.5504/BBEQ.2012.0112
        16. Nelly Manolova, Soren Hayrabedyan, Krassimira Todorova, Diana Zasheva, Milena Mourjeva, Stanimir Kyurkchiev, Maria Stamenova: In search of factors in endometriosis peritoneal fluid that decreased decidualization process. 01/2013; 66(1-1):153-158. DOI:10.7546/CR-2013-66-1-13101331-20
        17. Soren Hayrabedyan, Milcho Mincheff, Diana Zasheva, Nelly Manolova, Krassimira Todorova: Autophagy Signalling is Differentially Modulated by miR-204 in Context of Innate Immunity Induction. 01/2013; 66(1-1):127-132. DOI:10.7546/CR-2013-66-1-13101331-16
        18. Krassimira Todorova, Milcho Mincheff, Soren Hayrabedyan, Jana Mincheva, Diana Zasheva, Aleksandar Kuzmanov, Nelson Fernández: Fundamental Role of microRNAs in Androgen-Dependent Male Reproductive Biology and Prostate Cancerogenesis. American Journal Of Reproductive Immunology 04/2012; 69(2). DOI:10.1111/j.1600-0897.2012.01139.x
        19. Patrick S Spencer, Soukaina M Hakam, Phillipe P Laissue, Asma Jabeen, Pallavi Jain, Soren Hayrabedyan, Krassimira Todorova, Alyssa Blanch, James M.W.R. McElhinney, Niwedhie Muhandiram, Shaza Alkhatib, Gill B Dealtry, Jose M Miranda-Sayago, Nelson Fernández: Key Cellular Components and Interactive Histocompatibility Molecules Regulating Tolerance to the Fetal Allograft. American Journal Of Reproductive Immunology 04/2012; 68(2):95-9. DOI:10.1111/j.1600-0897.2012.01138.x
        20. Soren Hayrabedyan, Krassimira Todorova, Shina Pashova, Margarita Mollova, Nelson Fernández: Sertoli Cell Quiescence – New Insights. American Journal Of Reproductive Immunology 04/2012; 68(6). DOI:10.1111/j.1600-0897.2012.01137.x
        21. Stanimir Kyurkchiev, Fulvio Gandolfi, Soren Hayrabedyan, Tiziana A L Brevini, Roumen Dimitrov, Justine S Fitzgerald, Asma Jabeen, Milena Mourdjeva, Stella M Photini, Patrick Spencer, Nelson Fernández, Udo R Markert: Stem Cells in the Reproductive System. American Journal Of Reproductive Immunology 04/2012; 67(6):445-62. DOI:10.1111/j.1600-0897.2012.01140.x
        22. K. Todorova, S. Hayrabedyan, J. Dineva, I. Vangelov, M. Ivanova, M. Mollova: Gene panel in human cumulus cells as a biomarker for successful in vitro procedures (vol 64, pg 1143, 2011). 03/2012; 93(2-2):123. DOI:10.1016/j.jri.2012.02.001
        23. K. Todorova, S. Hayrabedyan, J. Dineva, I. Vangelov, D. Zasheva, V. Penchev, G. Nikolov, M. Mollova, M. Ivanova: Cumulus biomarker evaluation for human oocyte quality prediction. Acta Medica Bulgarica 01/2012; 39(1):70-76.
        24. K. Todorova, N. Manolova, D. Zasheva, S. Hayrabedyan: A relationship between microRNA204 and occludin in prostate cancer inflammation signaling. Acta Medica Bulgarica 01/2012; 39(2-2):23-28.
        25. Krasimira Todorova, Milcho Mincheff, Diana Zasheva, Soren Hayrabedyan: The role of miR-204 and nod1 receptor in prostate cancer inflammation signalling. 01/2012; 65(12-12):1739-1744.
        26. Soren Hayrabedyan, Boyko Georgiev, Dimitrina Kacheva, Mihail Chervenkov, Kiril Shumkov, Paulina Taushanova, Elena Kistanova: Flowcytometry as a method for advanced evaluation of boar semen. 01/2012; 65(4-4):541-548.
        27. Boyko Georgiev, Soren Hayrabedyan, Krassimira Todorova, Diana Zasheva, Paulina Taushanova, Dimitrina Kacheva, Peter J. Hansen: Sperm proteins as potential markers of boar fertility. 01/2012; 65(4-4):533-540.
        28. Krassimira Todorova, Diana Zasheva, Soren Hayrabedyan, Julieta Dineva, Ivailo Vangelov, Valentin Penchev, Georgi Nikolov, Margarita Mollova, Maria Ivanova: Gene panel in human cumulus cells as biomarker for successful in vitro procedures. 01/2011; 64(8-8):1143-1150.
        29. K. Todorova, I. Georgiev, J. Dineva, V. Penchev, S. Hajrabedyan, G. Nikolov, M. Molova, M. Ivanova: Lysil oxidase as a potential biomarker for predicting oocyte quality.
        30. V S Sarafian, Y Uzunova, S Hayrabedyan, P Ganchevska, M Filipova, I Filipov, L Lukanov, S Vladimirov: Histo-blood group antigen expression and proliferative activity of fibroblasts treated with dental monomers. Cell Biology and Toxicology 02/2008; 24(1):27-37. DOI:10.1007/s10565-007-9013-2
        31. Milen Karaivanov, Krasimira Todorova, Soren Hayrabedyan: Immunohistochemical quantitative assesment of the expression of GSTP1, iNOS and COX-2 in PIA, PIN and carcinoma in the prostate gland. 01/2008; 452:S186.
        32. Soren Hayrabedyan, Stanimir Kyurkchiev, Ivan Kehayov: Calcium-binding protein S100A13 is overexpressed in endometriosis. 01/2008; 61(2-2):281-288.
        33. Dobroslav Kyurkchiev, Ekaterina Ivanova-Todorova, Soren Hayrabedyan, Iskra Altankova, Stanimir Kyurkchiev: Female Sex Steroid Hormones Modify Some Regulatory Properties of Monocyte‐Derived Dendritic Cells. American journal of reproductive immunology (New York, N.Y.: 1989) 12/2007; 58(5):425-33. DOI:10.1111/j.1600-0897.2007.00526.x
        34. M Karaivanov, K Todorova, A Kuzmanov, S Hayrabedyan: Quantitative immunohistochemical detection of the molecular expression patterns in proliferative inflammatory atrophy. Journal of Molecular Histology 04/2007; 38(1):1-11. DOI:10.1007/s10735-006-9070-5
        35. Aleksandar Kuzmanov, Soren Hayrabedyan, Milen Karaivanov, Krassimira Todorova: Basal cell subpopulation as putative human prostate carcinoma stem cells. Folia Histochemica et Cytobiologica 02/2007; 45(2):75-80.
        36. K. Todorova, T. Shamov, S. Hayrabedyan, A. Kuzmanov, S. Kyurkchiev, I. Kehayov: Quantitative evaluation of angiogenesis in globlastoma with CD105. 01/2007; 60(5-5):575-578.
        37. Krassimira Todorova, Soren Hayrabedyan, Todor Shamov, Milen Karaivanov, Alexandar Kuzmanov, Stanimir Kyurkchiev, Ivan Kehayov: Quantitative evaluation of AMACR in gliobastoma. 01/2007; 60(10-10):1123-1126.
        38. K. Todorova, S. Hayrabedyan, I. Kehayov, S. Kyurkchiev: Quantitive assessment of the expression levels of PSMA, hCG and endoglin in prostate carcinoma tissues. Clinical Application of Immunology 10/2006; 5(1-1):543-547.
        39. M. Karaivanov, K. Todorova, A. Kuzmanov, S. Hayrabedyan, I. Kehayov, S. Kyurkchiev: Immunohistochemical comparative analysis of the expression of p63, amacr, COX-2 and GSTP1 in proliferative inflammatory atrophy, prostate intraepithelial neoplasia and prostate carcinoma. Differential diagnosis and predicative significance. 01/2006; 59(8):885-890.
        40. S. Hayrabedyan, S. Kyurkchiev, I. Kehayov: Evaluation of IL-1 alpha expression in endometriotic lesions using quantitative immunohistochemistry approach. 01/2006; 59(2):229-234.
        41. Soren Hayrabedyan, Stanimir Kyurkchiev, Ivan Kehayov: FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis. Journal of Reproductive Immunology 11/2005; 67(1-2):87-101. DOI:10.1016/j.jri.2005.07.001