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Skillman, Kristen

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Skillman

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Kristen

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Skillman, Kristen
Author's Publications: search.filters.isAuthorOfPublication.99c77c25-5312-4a04-bfbc-24d2b923982a

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    Functional Analysis of Sirtuin Genes in Multiple Plasmodium falciparum Strains
    (Public Library of Science, 2015) Merrick, Catherine J.; Jiang, Rays H. Y.; Skillman, Kristen; Samarakoon, Upeka; Moore, Rachel M.; Dzikowski, Ron; Ferdig, Michael T.; Duraisingh, Manoj
    Plasmodium falciparum, the causative agent of severe human malaria, employs antigenic variation to avoid host immunity. Antigenic variation is achieved by transcriptional switching amongst polymorphic var genes, enforced by epigenetic modification of chromatin. The histone-modifying ‘sirtuin’ enzymes PfSir2a and PfSir2b have been implicated in this process. Disparate patterns of var expression have been reported in patient isolates as well as in cultured strains. We examined var expression in three commonly used laboratory strains (3D7, NF54 and FCR-3) in parallel. NF54 parasites express significantly lower levels of var genes compared to 3D7, despite the fact that 3D7 was originally a clone of the NF54 strain. To investigate whether this was linked to the expression of sirtuins, genetic disruption of both sirtuins was attempted in all three strains. No dramatic changes in var gene expression occurred in NF54 or FCR-3 following PfSir2b disruption, contrasting with previous observations in 3D7. In 3D7, complementation of the PfSir2a genetic disruption resulted in a significant decrease in previously-elevated var gene expression levels, but with the continued expression of multiple var genes. Finally, rearranged chromosomes were observed in the 3D7 PfSir2a knockout line. Our results focus on the potential for parasite genetic background to contribute to sirtuin function in regulating virulence gene expression and suggest a potential role for sirtuins in maintaining genome integrity.
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    Demographic and clinical profiles of Plasmodium falciparum and Plasmodium vivax patients at a tertiary care centre in southwestern India
    (BioMed Central, 2016) Chery, Laura; Maki, Jennifer N.; Mascarenhas, Anjali; Walke, Jayashri T.; Gawas, Pooja; Almeida, Anvily; Fernandes, Mezia; Vaz, Marina; Ramanan, Rakesh; Shirodkar, Diksha; Bernabeu, Maria; Manoharan, Suresh Kumar; Pereira, Ligia; Dash, Rashmi; Sharma, Ambika; Shaik, Riaz Basha; Chakrabarti, Rimi; Babar, Prasad; White, John; Mudeppa, Devaraja G.; Kumar, Shiva; Zuo, Wenyun; Skillman, Kristen; Kanjee, Usheer; Lim, Caeul; Shaw-Saliba, Kathryn; Kumar, Ashwani; Valecha, Neena; Jindal, V. N.; Khandeparkar, Anar; Naik, Pradeep; Amonkar, Sunanda; Duraisingh, Manoj; Tuljapurkar, Shripad; Smith, Joseph D.; Dubhashi, Nagesh; Pinto, Roque G. W.; Silveria, Maria; Gomes, Edwin; Rathod, Pradipsinh K.
    Background: Malaria remains an important cause of morbidity and mortality in India. Though many comprehensive studies have been carried out in Africa and Southeast Asia to characterize and examine determinants of Plasmodium falciparum and Plasmodium vivax malaria pathogenesis, fewer have been conducted in India. Methods: A prospective study of malaria-positive individuals was conducted at Goa Medical College and Hospital (GMC) from 2012 to 2015 to identify demographic, diagnostic and clinical indicators associated with P. falciparum and P. vivax infection on univariate analysis. Results: Between 2012 and 2015, 74,571 febrile individuals, 6287 (8.4%) of whom were malaria positive, presented to GMC. The total number of malaria cases at GMC increased more than two-fold over four years, with both P. vivax and P. falciparum cases present year-round. Some 1116 malaria-positive individuals (mean age = 27, 91% male), 88.2% of whom were born outside of Goa and 51% of whom were construction workers, were enroled in the study. Of 1088 confirmed malaria-positive patients, 77.0% had P. vivax, 21.0% had P. falciparum and 2.0% had mixed malaria. Patients over 40 years of age and with P. falciparum infection were significantly (p < 0.001) more likely to be hospitalised than younger and P. vivax patients, respectively. While approximately equal percentages of hospitalised P. falciparum (76.6%) and P. vivax (78.9%) cases presented with at least one WHO severity indicator, a greater percentage of P. falciparum inpatients presented with at least two (43.9%, p < 0.05) and at least three (29.9%, p < 0.01) severity features. There were six deaths among the 182 hospitalised malaria positive patients, all of whom had P. falciparum. Conclusion: During the four year study period at GMC, the number of malaria cases increased substantially and the greatest burden of severe disease was contributed by P. falciparum.