German Cancer Research Centre - DKFZ
The goal of our research is to understand the molecular underpinnings of human disease, particularly those caused by microbial pathogens, and especially as they relate to human carcinogenesis. We use X-ray crystallography as a foundational tool for a "bottom-up" approach to these questions, examining pathogenic proteins and their interactions with host molecules at the molecular level.
Much of our work has to-date centered on bacterial pathogenesis, in particular bacteria utilizing specialized protein delivery systems, so-called "injectosomes" or "molecular syringes", machineries that translocate bacterial factors into eukaryotic cells to modulate host biochemistry for the benefit of the pathogen. Many of these factors are proven genotoxins or agents impacting oncogenic growth regulatory factors in the cell.
We have also investigated the African trypanosome (T. brucei), the causative agent of sleeping sickness. T. brucei repeatedly evades immune recognition through cycles of switching the extremely dense VSG surface protein, effectively changing its molecular appearance to the immune system through somatic, real-time "coat switching." We are using structural biology to examine the dynamic nature of this immune system-pathogen dynamic adaptational process. Our long-term goal is to develop paradigms for immune-evasion by pathogenic cell-types at the molecular level, which we hope will inform studies of immune-evasion in other contexts such as cancer.
Mugnier, M.R., Stebbins, C.E., Papavasiliou, F.N. (2016). Masters of Disguise: Antigenic Variation and the VSG Coat in Trypanosoma brucei. PLoS Pathog., 12(9):e1005784. doi: 10.1371/journal.ppat.1005784
Notti, R.Q., Stebbins, C.E. (2016). The Structure and Function of Type III Secretion Systems. Microbiol Spectr. 4(1). doi: 10.1128/microbiolspec.VMBF-0004-2015.
Notti, R.Q., Bhattacharya, S., Lilic, M., Stebbins, C.E. (2015). A common assembly module in injectisome and flagellar type III secretion sorting platforms. Nat Commun. 6:7125. doi: 10.1038/ncomms8125.
Nešic, D., Buti, L., Lu, X., Stebbins, C.E. (2014). Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2. Proc Natl Acad Sci U S A. 111(4):1562-7. doi: 10.1073/pnas.1320631111.