Education and Training
Ya-Ping received her M.S. in Physiology, Medical School from National Taiwan University, Taiwan in 1999. After two years of training in Cancer Immunology in Academia Sinica, Taiwan, she pursued and received her Ph.D. in Biochemistry from University of Cologne, Germany in 2005 with focus on extracellular matrix biology under the mentorship of Prof. Mats Paulsson and Raimund Wagener. In 2006, she joined Dr. Magnus Hook’s group and launched her research in molecular pathogenesis of infectious diseases with emphasis on host-pathogen interactions. Currently her efforts expanded to harness innate immune evasion of microbe with particular focuses on complement evasion and phagocytosis inhibition.
Dr. Ko’s research is focused on determining the molecular pathogenesis of infectious diseases with emphasis on innate immune modulation of bacteria proteins. The manifestation and progression of infectious diseases are the outcomes of complex interactions between bacteria factors and host proteins. Currently, there are two lines of research.
1. Penetrating the Staph Fibrinogen Shield. Staphylococcus aureus is an opportunistic pathogen that is capable of causing life-threatening disease and the emergence of antibiotic resistant strains (i.e. MRSA) highlights the need for novel and effective therapeutics. All S. aureus vaccines tested so far have been ineffective and we think we now know why. We have discovered that S. aureus assembles a shield around itself containing the host protein, fibrinogen. This shield protects the microbe from being killed and removed by the host defense systems. We believe this shield is a likely cause for the failure of all clinical trials that have focused on using antibody vaccination strategies. The goals of the project are to understand the mechanisms used by the bacteria in forming the protective fibrinogen shield and we are exploring strategies to prevent its formation.
2. Bacterial evasion of the complement system. The complement system is not only the first line of defense against microorganisms, but also an important arm of our innate immune response. Complement factors circulate in our plasma in an inactive form, but are rapidly activated upon contact with invading microorganisms or altered self-surfaces. The activation of the complement system has three important outcomes: A) labeling of bacteria with C3b for efficient uptake by phagocytes; B) generation of chemoattractant molecules (C3a/C5a) to recruit immune cells to the sites of infection; C) formation of membrane attach complex for direct killing of Gram-negative Bacteria. Research in lab demonstrated that bacteria proteins, including surface proteins and secreted proteins, not only binds host plasma protein fibrinogen but also recruits complement factors. The goals are to understand the molecular mechanism of the interactions and the precise biological functions of the interactions. One area of deep interest is to elucidate how bacteria manipulate fibrinogen-centered coagulation system and complement system simultaneously to tip these two important host defense mechanisms in favor of bacteria.
1. Ko, Y. P., Kang, M., Ganesh, V. K., Ravirajan, D., Li, B., and Hook, M. (2016) Coagulase and Efb of Staphylococcus aureus Have a Common Fibrinogen Binding Motif. MBio 7
2. Prasad, J. M., Gorkun, O. V., Raghu, H., Thornton, S., Mullins, E. S., Palumbo, J. S., Ko, Y. P., Hook, M., David, T., Coughlin, S. R., Degen, J. L., and Flick, M. J. (2015) Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense. Blood 126, 2047-2058
3. Neacsu, C. D., Ko, Y. P., Tagariello, A., Rokenes Karlsen, K., Neiss, W. F., Paulsson, M., and Wagener, R. (2014) Matrilin-1 is essential for zebrafish development by facilitating collagen II secretion. J. Biol. Chem. 289, 1505-1518
4. Ko, Y. P., Kuipers, A., Freitag, C. M., Jongerius, I., Medina, E., van Rooijen, W. J., Spaan, A. N., van Kessel, K. P., Hook, M., and Rooijakkers, S. H. (2013) Phagocytosis escape by a Staphylococcus aureus protein that connects complement and coagulation proteins at the bacterial surface. PLoS Pathog 9, e1003816
5. Kang, M., Ko, Y. P., Liang, X., Ross, C. L., Liu, Q., Murray, B. E., and Hook, M. (2013) Collagen-binding microbial surface components recognizing adhesive matrix molecule (MSCRAMM) of Gram-positive bacteria inhibit complement activation via the classical pathway. J. Biol. Chem. 288, 20520-20531* co-first authorship
6. Ko, Y. P., Liang, X., Smith, C. W., Degen, J. L., and Hook, M. (2011) Binding of Efb from Staphylococcus aureus to fibrinogen blocks neutrophil adherence. J. Biol. Chem. 286, 9865-9874
7. Ganesh, V. K., Rivera, J. J., Smeds, E., Ko, Y. P., Bowden, M. G., Wann, E. R., Gurusiddappa, S., Fitzgerald, J. R., and Hook, M. (2008) A structural model of the Staphylococcus aureus ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics. PLoS Pathog 4, e1000226
8. Nicolae, C., Ko, Y. P., Miosge, N., Niehoff, A., Studer, D., Enggist, L., Hunziker, E. B., Paulsson, M., Wagener, R., and Aszodi, A. (2007) Abnormal collagen fibrils in cartilage of matrilin-1/matrilin-3-deficient mice. J. Biol. Chem. 282, 22163-22175
9. Wagener, R., Ehlen, H. W., Ko, Y. P., Kobbe, B., Mann, H. H., Sengle, G., and Paulsson, M. (2005) The matrilins--adaptor proteins in the extracellular matrix. FEBS Lett. 579, 3323-3329
10. Ko, Y. P., Kobbe, B., Paulsson, M., and Wagener, R. (2005) Zebrafish (Danio rerio) matrilins: shared and divergent characteristics with their mammalian counterparts. Biochem. J. 386, 367-379
11. Chang, Y. W., Chen, S. C., Cheng, E. C., Ko, Y. P., Lin, Y. C., Kao, Y. R., Tsay, Y. G., Yang, P. C., Wu, C. W., and Roffler, S. R. (2005) CD13 (aminopeptidase N) can associate with tumor-associated antigen L6 and enhance the motility of human lung cancer cells. Int. J. Cancer 116, 243-252
12. Wu, C. H., Balasubramanian, W. R., Ko, Y. P., Hsu, G., Chang, S. E., Prijovich, Z. M., Chen, K. C., and Roffler, S. R. (2004) A simple method for the production of recombinant proteins from mammalian cells. Biotechnol. Appl. Biochem. 40, 167-172
13. Ko, Y., Kobbe, B., Nicolae, C., Miosge, N., Paulsson, M., Wagener, R., and Aszodi, A. (2004) Matrilin-3 is dispensable for mouse skeletal growth and development. Mol. Cell. Biol. 24, 1691-1699
14. Kao, Y. R., Shih, J. Y., Wen, W. C., Ko, Y. P., Chen, B. M., Chan, Y. L., Chu, Y. W., Yang, P. C., Wu, C. W., and Roffler, S. R. (2003) Tumor-associated antigen L6 and the invasion of human lung cancer cells. Clin. Cancer Res. 9, 2807-2816