David Serre, PhD, Genomic Medicine Institute (GMI), and Peter Zimmerman, PhD, Case Western Reserve University School of Medicine, are part of an international team of researchers that sequenced the genomes of Plasmodium vivax parasites, which cause up to 250 million cases of malaria per year. The researchers reported their findings in the Sept. 6 issue of PLoS Neglected Tropical Diseases.
Using next-generation sequencing techniques, Dr. Serre and Ernest R. Chan, PhD, GMI, sequenced the genomes of P. vivax extracted from the blood of two malaria patients in Madagascar and three in Cambodia . For comparison, they sequenced P. vivax from a monkey that had been infected with a human strain of the parasite found in South America.
"Our work provides the first report on genome-wide variation of this malaria parasite and provides the malaria research community with more than 80,000 genetic markers that can now be used for trait mapping or population monitoring,” Serre said. The data will be used for several ongoing studies to advance the understanding of P. vivax biology. The genetic markers can be used to search for links to drug-resistant malaria, a growing problem in Southeast Asia, and to study possible new treatments for P. vivax malaria; the researchers will perform evolutionary genetic studies to learn where the parasite originated, how it spreads, and how different strains are geographically distributed; and the team will study evolving P. vivax infection mechanisms.
Even though the parasites tested came from three continents, their genomes shared remarkable similarities. “The parasite’s life cycle enables P. vivax to be a microbial globe-trotter," said Dr. Zimmerman. It gets into the red blood cells and makes people sick, he explained. When they feel better, people resume their normal activities and begin to travel. However, the parasite may lay dormant in the liver for months or a year and can reemerge into the blood when that person is in a different location. “In that new place, local mosquitoes bite, become infected, and start spreading the P. vivax parasite and its genome in locations that can be a long distance away from where the original human infection occurred,” Dr. Zimmerman said.
Breast cancer is the second leading cause of cancer deaths among women, and the highly aggressive, highly metastatic triple-negative breast cancers (TNBCs) are particularly lethal because of their propensity to spread to other tissues. Khalid Sossey-Alaoui, PhD, Molecular Cardiology, and colleagues recently made an important discovery that could help uncover some of the complex mechanisms involved in TNBC metastasis and could lead to a new tool for early detection of the deadly disease.
Dr. Sossey-Alaoui and his team found that the protein WAVE3, a regulator of cell motility, is required for cancer cells to metastasize and is highly elevated in patients with TNBCs. A key component in the metastatic potential of tumors is their invasiveness, or how aggressively the tumor cells seek new locations throughout the body. Dr. Sossey-Alaoui and colleagues found that WAVE3 is one of the factors that drive the invasive properties of TNBC cells. This finding helps to uncover the complex cascade of events that lead to metastasis, and could greatly influence the study of the biology of TNBCs. Dr. Sossey-Alaoui’s results, published in the August issue of PLoS One , provide preliminary data for an upcoming National Institutes of Health (NIH) R01 application.
In addition to the important biological implications of these findings, Dr. Sossey-Alaoui’s team has, for the first time, uncovered a biomarker that can detect TNBCs in very early stages, perhaps even before a patient shows symptoms of disease. WAVE3, the team found, is abundant in the blood of patients with TNBCs; therefore, its presence can potentially be used as a diagnostic tool in individuals who are predisposed to the cancers. This porti on of the studies were funded by a U.S. Department of Defense Breast Cancer Idea Award, and, due to the high commercialization potential of the findings, Dr. Sossey-Alaoui has submitted a proposal to Cleveland Clinic Innovations for support in developing a diagnostic kit and bringing the technology to market.
Dr. Sossey-Alaoui’s discoveries not only open new avenues of study in the complex field of cancer biology, but they have enormous clinical application and real, life-saving potential. Li Zhang, PhD, Quantitative Health Sciences, is a coauthor on the PLoS One paper, and Dr. Sossey-Alaoui credits Ed Plow, PhD, Chair, Molecular Cardiology, for his support for this project.