Research

Carbohydrate utilization and storage by protozoan parasites

Glycogen is a branched polymer of glucose that functions as a store of both energy and carbon skeletons in many species ranging from mammals to bacteria. In collaboration with the laboratory of Dr. Wayne Wilson (Department of Biochemistry and Nutrition) we have begun a study of the role of glycogen stores in the protists Trichomonas vaginalis and Giardia intestinalis. These organisms are both of medical interest. T. vaginalis is the causative agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide where G. intestinalis infection is an important cause of diarrheal illness. Both organisms have been shown to accumulate substantial quantities of glycogen at particular points during growth. Our current work addresses the kinetics of glycogen synthesis and utilization as well as the cellular mechanisms that regulate these processes.

Additionally, we have begun to characterize a family of alpha-amylases present in T. vaginalis. We are particularly interested in determining if alpha-amylases play a role in nutrient acquisition within the glycogen rich environment of the vagina.

Endothelin-1 production by macrophages

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide, first purified from the conditioned media of cultured endothelial cells. Since its identification, most studies have focused on the role of ET-1 in cardiovascular physiology and pathophysiology. Elevated plasma and tissue levels of ET-1 have been noted in numerous pathologies, including cardiopulmonary diseases (pulmonary hypertension, congestive heart failure, cardiomyopathy), as well as systemic and localized inflammatory conditions such as bronchial asthma, arthritis, inflammatory bowel disease, atherosclerosis, and sepsis.

My lab has begun to investigate macrophages as an alternative source of ET-1, particularly during inflammatory diseases. We have identified roles for Toll-like receptors (TLRs) and MAP Kinase signaling pathways in regulating the macrophage production of ET-1 in response to encountering bacterial pathogens.  Additionally we have begun to characterize the expression of multiple isoforms of endothelin converting enzyme (ECE), an enzyme essential for the secretion of biologically active ET-1, by macrophages.

2012 research

Work in my lab is focused on carbohydrate utilization and storage by protozoan parasites. I am particularly interested in glycogen utilization by several important human pathogens. As a branched polymer of glucose, glycogen functions as a store of both energy and carbon skeletons in many species ranging from mammals to bacteria. In collaboration with the laboratory of Dr. Wayne Wilson (Department of Biochemistry and Nutrition) we have begun a study of the role of glycogen stores in the protists Trichomonas vaginalis and Giardia intestinalis. These organisms are both of medical interest. T. vaginalis is the causative agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide where G. intestinalis infection is an important cause of diarrheal illness. Both organisms have been shown to accumulate substantial quantities of glycogen at particular points during growth. Our current work addresses the kinetics of glycogen synthesis and utilization as well as the cellular mechanisms that regulate these processes.  Additionally, we have begun to characterize several families of amylases present in T. vaginalis. We are particularly interested in determining if these enzymes play a role in nutrient acquisition within the glycogen rich environment of the human vagina.

2011 research

My lab is interested in all aspects of the host-pathogen interaction. One project focuses on the regulation of cytokine production by macrophages in response to microbial challenge. A second focuses on the molecular and cell biology of parasitic protozoa, including their interaction with insect vectors, and nutrient acquisition from their environment.

Publications

Pradhan, P., Lundgren, S.W., Wilson, W.A., Brittingham, A. 2011. Glycogen Storage and Degradation During in vitro Growth and Differentiation of Giardia intestinalis. Journal of Parasitology (in press)., 2011

Divino, J.N., Chawla, K.S., da Silva, C.M., Bjorge, A.M., and Brittingham, A. 2010. Endothelin-1 production by the canine macrophage cell line DH82: Enhanced production in response to microbial challenge. Veterinary Immunology and Immunopathology 136: 127-132., 2010

Wahl, J.R., Goetsch, N.J., Young, H.J., Van Maanen, R.J., Johnson, J.D., Pea, A.S., and Brittingham, A. Murine macrophages produce endothelin-1 (ET-1) after microbial stimulation. Experimental Biology and Medicine 230(9): 652-658. , 2005

Scolaro, E.J., Ames, R.P., and Brittingham, A. Growth-phase dependent substrate adhesion in Crithidia fasciculata. The Journal of Eukaryotic Microbiology 52(1): 17-22. , 2005

Yao, C., Leidal, K.G., Brittingham, A., Tarr, D.E., Donelson, J.E., and Wilson, M.E. Biosynthesis of the major surface protease GP63 of Leishmania chagasi. Molecular and Biochemical Parasitology 121(1): 119-28. , 2002

Bagentose, L.M., Mentink-Kane, M.M., Brittingham, A., Mosser, D.M., and Monestier, M. Mercury enhances susceptibility to murine leishmaniasis. Parasite Immunology 23(12): 633-640. , 2001

Brittingham, A., Miller, M.A., Donelson, J.E., and Wilson, M.E. Regulation of GP63 mRNA stab ility in promastigotes of virulent and attenuated Leishmania chagasi. Molecular and Biochemical Parasitology 112(1): 51-59. , 2001

Awards and honors

2005 - Outstanding University Researcher Award – DMU Faculty Award