Adjunct Professor of Immunology and Infectious Diseases
Professor of Biology, Boston College
Associated Researcher, Broad Institute
Malaria and other diseases transmitted by mosquitoes and other vector insects impose substantial morbidity and mortality on human populations around the globe. The renewed call for malaria eradication, and the integration of genomics with studies of vector and parasite biology, provide a variety of new opportunities to understand in greater depth the basic biology of malaria and to develop new approaches to reducing disease incidence and monitoring the effectiveness of existing and evolving interventions being deployed to eliminate malaria.
Malaria vector genomics and genetic associations
We are developing and utilizing genomically-based tools to understand population and species structure in malaria vectors, and to map genetic associations for key traits (e.g., vector competence, host preference, insecticide resistance) in vector mosquitoes that affect malaria transmission and vector control. On-going projects include use a genome-wide single nucleotide polymorphism array for Anopheles gambiae we have developed with collaborators to map population structure and genetic associations, genomic analysis of species complexity among anopheline mosquitoes, and development of methods for discovery of genetic associations based on direct sequencing of well-defined mosquito phenotype pools.
Genetics and mechanisms of insecticide resistance
The use of insecticides, in insecticide-treated bed nets and indoor residual spraying, remains our most effective tool for reducing malaria incidence, but development of insecticide resistance in vector mosquitoes threatens to compromise the effectiveness of these tools. We are taking a number of approaches to investigating mechanisms and incidence of insecticide resistance in vector mosquitoes. On-going projects include collaborative efforts to map genetic variation associated with insecticide resistance in African vector mosquitoes, and the use of forward genetics to define mechanisms underlying target-site and metabolic resistance in anopheline vector mosquitoes and the model fruit fly Drosophila melanogaster.
Malaria parasite proteasome function
Development of new anti-malarial drugs will be accelerated by identification of “druggable” targets and processes in malaria parasites. We are investigating the function of the proteasome in Plasmodium falciparum to better understand its roles in parasite development, with an emphasis on asexual parasite stages that arise during erythrocytic parasite development. On-going projects include the use of small-molecule inhibitors to define the functional roles of the proteasome during blood-stage parasite development, analysis of ubiquitylation during parasite development, and genetic analysis of the development of resistance to proteasome inhibitors in malaria parasites.
Bartholomay, L.C., Waterhouse, R.M., Mayhew, G.F., Campbell, C.L., Michel, K., Zou, Z., Ramirez, J.L., Das, S., Alvarez, K., Arensburger, P., Bryant, B., Chapman, S.B., Dong, Y., Erickson, S.M., Karunaratne, S.H.P.P., Kokoza, V., Kodira, C.D., Pignatelli, P., Shin, S.W., Vanlandingham, D.L., Atkinson, P.W., Birren, B., Christophides, G.K., Clem, R.J., Hemingway, J., Higgs, S., Megy, K., Ranson, H., Zdobnov, E.M., Raikhel, A.S., Christensen, B.M., Dimopoulos, G., and Muskavitch, M.A.T. 2010. Pathogenomics of Culex quinquefasciatus and meta-analysis of infection responses to diverse pathogens. Accepted for publication in Science.
Arensburger, P., Megy, K., Waterhouse, R.M., Abrudan, J., Amedeo, P., Antelo, B., Bartholomay, L.C., Bidwell, S., Caler, E., Camara, F., Casola, C., Castro, M.T., Chandramouliswaran, I., Chapman, S.B., Christley, S., Costas, J., Eisentstadt, E., Feshotte, C., Fraser-Liggett, C., Guigo, R., Haas, B., Hanson, B.S., Hemingway, J., Hill, S., Howarth, C., Ignell, R., Kennedy, R.C., Kodira, C.D., Lobo, N.F., Mao, C., Mayhew, G.F., Michel, K., Mori, A., Nannan, L., Naverira, H., Nene, V., Nguyen, N., Pearson, M.D., Pritham, E., Puiu, D., Qi, Y., Ribeiro, J., Roberston, H.M., Severson, D.W., Shumway, M., Stanke, M., Strausberg, B., Sun, C., Sutton, G., Tu, Z.J., Tubio, J.M.C., Unger, M.F., Vanlandingham, D.L., Vilella, A.J., White, O., White, J.R., Wortman, J., Birren, B., Christensen, B.M., Collins, F.H., Cornel, A., Dimopoulos, G., Hannick, L.I., Higgs, S., Lanzaro, G., Lee, N., Muskavitch, M.A.T., Raikhel, A.S., and Atkinson, P.W. 2010. Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics. Accepted for publication in Science.
Shalaby, N.A., Parks, A.L., Morreale, E.J., Osswalt, M.C., Pfau, K.M., Pierce, E.L., and Muskavitch, M.A. 2009. A screen for modifiers of Notch signaling uncovers Amun, a protein with a critical role in sensory organ development. Genetics 182(4): 1061–76 (PubMed abstract).
Parks, A.L., Shalaby, N., and Muskavitch, M.A. 2008. Notch and Suppressor of Hairless regulate levels but not patterns of Delta expression in Drosophila. Genesis 46: 265–275 (PubMed abstract).
Muskavitch, M.A.T., Barteneva, N., and Gubbels, M.J. 2008. Chemogenomics and parasitology: small molecules and cell-based assays to study infectious processes. Combinatorial Chemistry & High Throughput Screening 11: 626–649.
Parks, A.L., Stout, J.R., Shepard, S.B., Klueg, K.M., Dos Santos, A.A., Parody, T.R., Vaskova, M., and Muskavitch, M.A.T. 2006. Structure-function analysis of Delta trafficking, receptor binding, and signaling inDrosophila. Genetics 174: 1947–1961 (PubMed abstract).
DeSilva, M., Muskavitch, M.A.T., and Roche, J. P. 2004. Print media coverage of antibiotic resistance. Science Communication 26: 31–43.
Muskavitch, M.A.T., and Roche, J. P. 2003. Limited precision in print media communication of West Nile virus risks. Science Communication 24: 353–365.
Klueg, K.M., Alvarado, D., Muskavitch, M.A.T., and Duffy, J.B. 2002. Creation of a GAL4/UAS-coupled inducible gene expression system for use in Drosophila cultured cell lines. Genesis 34: 119–122 (PubMed abstract).
Pavlopoulos, E., Pitsouli, C., Klueg, K., Muskavitch, M.A.T., Moschonas, N. and Delidakis, C. 2001. neuralised encodes a peripheral membrane protein involved in Delta signalling and endocytosis. Developmental Cell 1: 807–816 (PubMed abstract).
Parks, A.L., Klueg, K.M., Stout, J.R. and Muskavitch, M.A.T. 2000. Ligand endocytosis drives receptor dissociation and activation in the Notch pathway. Development 127: 1373–1385 (PubMed abstract).
Helms, W., Lee, H., Ammerman, M., Parks, A.L., Muskavitch, M.A.T., and Yedvobnick, B. 1999. Engineered truncations in the Drosophila Mastermind protein disrupt Notch pathway function. Developmental Biology 215: 358–374 (PubMed abstract).
Klueg, K.M., and Muskavitch, M.A.T. 1999. Ligand-receptor interactions and trans-endocytosis of Delta, Serrate, and Notch: members of the Notch signalling pathway in Drosophila. Journal of Cell Science 112: 3289–3297 (PubMed abstract).
Jacobsen, T.L., Brennan, K., Arias, A.M., and Muskavitch, M.A.T. 1998. Cis-interactions between Delta and Notch modulate neurogenic signalling in Drosophila. Development 125: 4531–4540 (PubMed abstract).
Klueg, K.M., Parody, T.R., and Muskavitch, M.A.T. 1998. Complex proteolytic processing acts on Delta, a transmembrane ligand for the Notch, during Drosophila development. Molecular Biology of the Cell 9: 1709–1723 (PubMed abstract).
Kopp, A., Muskavitch, M.A.T., and Duncan, I. 1997. The roles of hedgehog and engrailed in patterning the adult abdominal segment of Drosophila. Development 124: 3703–3714 (PubMed abstract).
Parks, A.L., Huppert, S.S., and Muskavitch, M.A.T. 1997. The dynamics of neurogenic signalling underlying bristle development in Drosophila melanogaster. Mechanisms of Development 63: 61–74 (PubMed abstract).
Huppert, S.S., Jacobsen, T.L., and Muskavitch, M.A.T. 1997. Feedback regulation is central to Delta-Notch signalling required for Drosophila wing vein morphogenesis. Development 124: 3283–3291 (PubMed abstract).