Training Years: 2013-2014
Training Site: University of Ghana
Country: Ghana
Mentor: Jonathan Stiles, PhD
Title: Genetic Polymorphism in Malaria Severity in Ghana
Project Objectives:
Hypothesis: HO-1, CXCL10/CXCR3 and STAT1/STAT3 variants mediate host protection against severity of Plasmodium infection.
Aim 1(a): To determine the role of HO-1, CXCL10/CXCR3 and STAT1/STAT3 variants in malaria severity HO-1, CXCL10/CXCR3 and STAT1/STAT3 exon and promoters from genomic DNA isolated from MM and CM patients with matching Healthy controls will be sequenced and analyzed and correlated with malaria severity. mRNA expression of HO-1, CXCL10/CXCR3 and STAT1/STAT3 studies will be conducted on lymphocytes isolated from MM and CM patients with matching Healthy controls to determine expression levels and correlate with malaria severity. Similarly, multiplexed immunoassay procedures will be used to assess protein expression of HO-1, CXCL10/CXCR3 and STAT1/STAT3 in serum and correlate with malaria severity.
Aim 1(b): To assess Heme/HO-1, CXCL10/CXCR3 and STAT1/STAT3 signaling pathways using Pathway Analysis software, hypothesis testing and assessment of correlation with malaria severity We will utilize case control study to compare Heme-induced gene expression networks in circulating plasma in MM and CM patients with matching Healthy controls. We plan to recruit approximately 1,000 patients and controls from the University of Ghana Medical School. Emphasis will be placed on HO-1, CD163, haptoglobin, IL10, G-CSF, CXCL4, Fox-3, IL2, STAT1, STAT3 as well as soluble cytokines and receptors. Potential genetic polymorphisms predisposing individuals to malaria severity will be identified.
Aim 2: To identify human copy number polymorphisms (CNPs) associated with severe malaria anemia (SMA) and other forms of severe malaria. We will use TaqMan Copy Number Assays combine TaqMan MGB probe chemistry with real-time PCR, which allow us to accurately quantify their copy number and determine if they are associated with SMA.
NIH Support: Fogarty fellowship postdoctoral training award
Career Development Award: K01-TW010282 (2016-2021) Role of Micrornas In Malaria And Sickle Cell Severity
