Date of Award
Master of Science (MS)
College of Science and Mathematics
Chemistry and Biochemistry
Thesis Sponsor/Dissertation Chair/Project Chair
John J. Siekierka
Carlos A. Molina
Nina M. Goodey
Lymphatic filariasis (or elephantiasis) is a major neglected disease with an estimated 120 million individuals infected and approximately 1.5 billion at risk in endemic regions. It is a highly disfiguring and debilitating disease and one of the major causes of global morbidity. Treatment options for this disease are few and new drug targets and therapies need to be identified. We have identified a protein kinase ortholog of human p38 mitogen-activated protein kinase (p38) expressed in the filarial parasite, Brugia malayi (B. malayi), one of three causative agent of lymphatic filariasis. We hypothesize that this protein kinase, BmMPKl, is important for the organism’s growth and viability and as such, may be a novel therapeutic target. Human p38 plays an essential role in responses to stress, such as toxins, infection and inflammation as well as cell cycle control and apoptosis. An ortholog found in the nematode, Caenorhabditis elegans (C. elegans, PMK-1/2), plays a similar role in protecting the organism from oxidative stress. Elimination of PMK-1/2 through genetic means results in the inability of C. elegans to respond to oxidative stress, disrupts neuronal development, and innate immune responses. Based on these and other observations we hypothesize that BmMPKl plays a similar role in protecting B. malayi from oxidative stress and in parasite growth and development.
The goals of this thesis project were: to produce recombinant BmMPKl kinase, assess the effects of known inhibitors of human p38 against BmMPKl, assess the effects of p38 inhibitors on B. malayi growth, replication, and response to oxidative stress.
Patel, Akruti, "A Novel Filarial Parasite (B. malayi) Stress-Activated Protein Kinase as a Potential Drug Target" (2010). Theses, Dissertations and Culminating Projects. 946.