Malaria Parasite Genomics, Development, Drug Resistance, Pathogenesis, and host-parasite interaction

2019-2020年，我们重点利用约氏疟原虫/小鼠模型研究疟疾发病的分子机制和信号通路。我们也有一个研究恶性疟原虫耐药机制的项目。

During the year of 2019-2020, we focused on studying the molecular mechanisms of malaria pathogenesis and signaling pathways using Plasmodium yoelii/mouse model. We also have a project studying mechanisms of drug resistance in Plasmodium falciparum. We have made good progresses in several projects: 1. We have completed a multi-year project dissecting the mechanism of Plasmodium yoelii erythrocyte binding-like protein (PyEBL) in regulating host innate response to malaria infections. This work was finally published in mBio after additional experiments and revision (mBio. 2020, 11:e02995-19). 2. We have finished another project studying a gene called March1 and published the work in Proc Natl Acad Sci U S A (2020, doi: 10.1073/pnas.2006492117) after extensive revision. This work shows MARCH1 is an important molecule that can regulate host type I interferon (IFN-I) response and T cell activation during malaria infections. Additionally, we have generated and cloned cell lines expressing luciferases, MAVS, and MARCH1 for screening small compound inhibitors. 3. Similarly, we have finished and published the work on receptor transporter protein 4 (RTP4). We show that RTP4 can regulate host IFN-I response during P. yoelii infections. Our work also suggests that RTP4 plays a critical role in brain pathogenesis during malaria parasite and West Nile virus infections. This work was again published in Proc Natl Acad Sci U S A recently (2020, doi: 10.1073/pnas.2006492117). 4. We continued to work on characterization of MMP3 function in malaria infections. MMP3 is highly up-regulated during infections of some P. yoelii strains. We are dissecting the mechanism of MMP3 in mediating inflammation in malaria. 5. We have been studying the molecular mechanism of malaria induced anemia. We have shown that infections with certain P. yoelii strains inhibit red blood cell (RBC) maturation. We are performing the last few experiments to complete a manuscript for publication. 6. We initiated a project investigating the functions of selected olfactory receptors (ORs) in malaria infections. We have identified 40 OR genes that may play a role in P. yoelii infections. 7. We have tagged several P. falciparum E3 ubiquitin ligases and showed that knocking-down some of the genes affects parasite responses to anti-malarial drugs. 8, Working with colleagues, I wrote an invited review on Plasmodium genomics and genetics that was published in Clin Microbiol Rev (2019 Jul 31;32(4). pii: e00019-19. doi: 10.1128/CMR.00019-19).