申请人从事疟疾寄生虫(疟原虫)耐药的遗传学研究和基因组修饰技术研究, 阐明了疟原虫耐药的多基因控制遗传机理，为克服疟疾耐药提供了理论基础和新思路。主要成绩如下：(1)建立了恶性疟原虫药物活性和耐药表型的高通量定量测定平台；“老药新用”策略发现若干高活性抗疟疾的已知药物（Yuan, et al, Nature Chemical Biology, 2009）；(2)发现Pfmdr1基因、Pfcrt基因和Pfdhfr基因是疟原虫对绝大部分不同化学结构的已知药物耐药的主效基因；验证联合用药克服Pfcrt突变导致的恶性疟原虫氯喹耐药，恢复氯喹药效（Yuan, et al, Science，2011）；(3) 建立了疟原虫CRISPR/Cas9基因组修饰工具，高效精准构建基因敲除、基因加标签和基因替换模型（mBio，2014）。共发表SCI论文16篇，其中以通讯作者/第一作者发表SCI论文8篇。

Drug resistance damaged the efforts in malaria prevention and control. Our research has been focus on the drug resistance in malaria parasite. To measure the parasite response to antimalarial drug/chemical in a fast and accurate way, we developed a high-throughput platform to quantitatively detect the IC50. Using this platform, we explored a library with all drugs approved for human or animal use, and repurposed some drugs with potent antimalarial activity. Combining using the linkage and association genetic mapping, we systematically screened and validated the genome-wide locus and genes conferring parasite drug resistance. Despite the diversity of promising compounds, resistance to them was governed by relatively few genes (Pfmdr1, Pfcrt and Pfdhfr). Mutations in Pfcrt conferring Chloroquine resistance were also found to confer sensitivity to some novel compounds. As a consequence, these novel compounds were effective against Chloroquine-resistant but not Chloroquine-sensitive parasites, thus resensitizing parasites to Chloroquine by combination usage. To look for an improved way to elucidate the gene function study, we developed the CRISPR/Cas9-mediated genome editing method, through which generating of genome modified parasite model with gene-deletion, gene tagging and gene replacement can be efficiently achieved in malaria parasite. Currently, to discovery new targets for new vaccine and drug design, we are carrying out systemically functional elucidating of G protein couple receptors predicted playing an important role in malaria parasite development and environment sensing. We have published 16 papers in academic journals, including corresponding author papers in mBio (2014) and first or co-first author papers in Science (2011), Nat. Chem. Biol.(2009), and co-author in PNAS (2010).