Xin-zhuan Su, Ph.D.
Chief, Malaria Functional Genomics Section
Senior Investigator
Malaria Functional Genomics Section
Dr. Su received his Ph.D. in parasitology from the University of Georgia in 1990 and joined NIAID's Laboratory of Parasitic Diseases in 1992. He became an investigator in the Laboratory of Malaria and Vector Research in 2001 and a senior investigator in 2006.
Description of Research Program
We are developing genome-wide approaches to study mechanisms of drug resistance, genome diversity, population genetics, and evolution of malaria parasites. One of our goals is to develop genome-wide single nucleotide polymorphism (SNP) and microsatellite (MS) genetic maps and use these maps to identify genes affecting phenotypes such as drug resistance, red blood cell invasion, and sexual development. A database of genome-wide polymorphisms from parasites collected around the world will be useful for studying parasite origin, transmission, and evolution.
Using parasites adapted to in vitro culture and a large number of genotypes obtained from the nuclear and mitochondrial genomes of Plasmodium falciparum, we are studying parasite population structure, evolutionary history, recombination pattern, and linkage disequilibrium. We have collected thousands of SNPs by sequencing multiple isolates and have developed a microarray chip to genotype parasite isolates collected from the field. We plan to measure different phenotypes of the parasites and perform association studies. For mapping drug-resistance genes that are likely under drug pressure, we will look for loci that are under selection. Indeed, we have shown reduced diversity in a large chromosomal region surrounding the pfcrt gene on chromosome 7, suggesting world-wide, drug-selective sweeps.
The sexual stages are vital phases in malaria parasite transmission and are the targets of various interventions such as transmission-blocking vaccines. The malaria parasite has a haploid genome when in the human host. The switch from asexual replication to sexual differentiation is likely to involve signal transduction and gene regulation. Recently, we used genetic mapping to identify a candidate gene that plays an important role in parasite sexual development. We are also interested in how this process is regulated and are using genetic mapping, microarray, and other approaches to study this complicated process.
Research Group Members
Selected Publications
(View list in PubMed.)
John C. Wootton, Xiaorong Feng, Michael T. Ferdig, Roland A. Cooper, Jianbing Mu, Dror Baruch, Alan J. Magill, and Xin-zhuan Su. (2002). Genetic diversity and chloroquine sweeps in the Plasmodium falciparum. Nature 418, 320-323.
Jianbing Mu, Junhui Duan, Kateryna Makova, Deirdre A. Joy, Huynh Q. Chuong, Oralee H. Branch, Wen-Hsiung Li, and Xin-zhuan Su. (2002). Chromosome-wide SNPs reveal an ancient origin of the human malaria parasite Plasmodium falciparum. Nature 418, 323-326.
Deirdre A. Joy, Xiaorong Feng, Jianbing Mu, Tetsuya Furuya, Kesinee Chotivanich, Antoniana U. Krettli, May Ho, Alex Wang, Nicholas J. White, Edward Suh, Peter Beerli, and Xin-zhuan Su. (2003). Early origin and recent expansion of the malaria parasite Plasmodium falciparum. Science 300, 318-321.
Tetsuya Furuya, Jianbing Mu, Karen Hayton, Anna Liu, Junhui Duan, Louis Nkrumah, Deirdre A. Joy, David A. Fidock, Hisashi Fujioka, Akhil B. Vaidya, Thomas E. Wellems, and Xin-zhuan Su. (2005). Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis. Proceedings of the National Academy of Sciences USA 102, 16813-16818.
Jianbing Mu, Philip Awadalla, Junhui Duan, Kate M. McGee, Jon Keebler, Karl Seydel, Gilean A. T. McVean and Xin-zhuan Su. (2007). Genome wide variation and identification of vaccine targets in the Plasmodium falciparum genome. Nature Genetics 39, 126-130.
Fangli Lu, Hongying Jiang, Jinhui Ding, Jianbing Mu, Jesus G. Valenzuela, José M. C. Ribeiro, and Xin-zhuan Su. (2007). cDNA sequences reveal considerable gene prediction inaccuracy in the Plasmodium falciparum genome. BMC Genomics (In press).
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