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Marc Muskavitch

professor of biology

Dr. Marc Muskavitch

Ph.D., Stanford University

Phone: 617-552-2717

Fields of Interest

Malaria and vector biology, vector mosquito genomics and genetics, malaria parasite proteasome function.

Academic Profile

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.

Representative Publications

Neafsey, D.E., Christophides, G.K., Collins, F.H., Emrich, S.J., Fontaine, M.C., Gelbart, W.M., Hahn, M.W., Howell, P.I., Kafatos, F.C., Lawson, D., Muskavitch, M.A.T., Waterhouse, R.M., Williams, L.J., and Besansky, N.J. 2013. The evolution of the Anopheles 16 genomes project. G3: Genes Ι Genomes Ι Genetics. Early Online May 24, 2013, doi:10.1534/g3.113.006247

Grant, A.J., Muskavitch, M.A.T. and O’Connell, R.J. 2013. Malaria infection does not affect the sensitivity of peripheral receptor neurons in Anopheles stephensi. Parasites & Vectors. 6:134. Epub ahead of print.

Nwakanma, D.C., Neafsey, D.E., Jawara, M., Adiamoh, M., Lund, E.A., Rodrigues, A., Loua, M.K., Konate, L., Sy, N., Dia, I., Awolola, T.S., Muskavitch, M.A.T., and Conway, D.J. 2013. Breakdown in the process of incipient speciation in Anopheles gambiae. Genetics. 193:1221-1231.

Reidenbach, K.R., Neafsey, D.E., Costantini, C., Sagnon, N., Muskavitch, M.A.T. and Besansky, N.J. 2012. Patterns of genomic differentiation between ecologically differentiated M and S forms of Anopheles gambiae in West and Central Africa. Gen. Biol. Evol. 4:1202-1212.

Kang, K., Panzano, V.C., Chang, E., Ni, L., Dainis, A.M., Jenkins, A.M., Regna, K., Muskavitch, M.A.T., and Garrity, P.A. 2012. Suppression of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila. Nature. 481:76-80.

Volkman, S.K., Ndiaye, D., Diakite, M., Koita, O., Davis D., Daniels, R., Park, D., Neafsey, D., Muskavitch, M.A.T., Krogstad, D.J., Sabeti, P., Hartl, D., Wirth, D.F. 2012. Application of genomics to field investigations of malaria by the International Centers for Excellence in Malaria Research. Acta Trop. 121:324-332.

Doumbia, S.O., Ndiaye, D., Koita, O.A., Diakité, M., Nwakanma, D., Coulibaly, M., Traoré, S.F., Keating, J., Milner, D.A., Ndiaye, J.L., Sene, P.D., Ahouidi, A., Dieye, T.N., Gaye, O., Okebe, J., Ceesay, S.J., Ngwa, A., Oriero, E.C., Konaté, L., Sy, N., Jawara, M., Faye, O., Kéita, M., Cissé, M., Sogoba, N., Poudiougou, B., Diawara, S., Sangaré, L., Coulibaly, T., Seck, I., Abubakar, I., Gomis, J., Mather, F.J., Sissako, A., Diarra, A., Kandeh, B., Whalen, C., Moyer, B., Nnedu, O., Thiero, O., Bei, A.K., Daniels, R., Miura, K., Long, C.A., Fairhurst, R.M., Duraisingh, M., Muskavitch, M.A.T., D'Alessandro, U., Conway, D.J., Volkman, S.K., Valim, C., Wirth, D.F. and Krogstad, D.J. 2012. Improving malaria control in West Africa: interruption of transmission as a paradigm shift. Acta Trop. 121:175-183.

Cessay, S.J., Bojang, K.A., Nwakanma, D., Conway, D.J., Koita, O.A., Doumbia, S.O., Ndiaye, D., Coulibaly, T.F., Diakité, M., Traoré, S.F., Coulibaly, M., Ndiaye, J.L., Sarr, O., Gaye, O., Konaté, L., Sy, N., Faye, B., Faye, O., Sogoba, N., Jawara, M., Dao, A., Poudiougou, B., Diawara, S., Okebe, J., Sangaré, L., Abubakar, I., Sissako, A., Diarra, A., Kéita, M., Kandeh, B., Long, C.A., Fairhurst, R.M., Duraisingh, M., Perry, R., Muskavitch, M.A.T., Valim, C., Volkman, S.K., Wirth, D.F. and Krogstad, D.J. 2011. Sahel, savanna, riverine and urban malaria in West Africa: similar control policies with different outcomes. Acta Trop. 121:175-183. Nov 19.

Daskalaki, A., Shalaby, N.A, Kux, K., Tsoumpekos, G., Tsibidis, G., Muskavitch, M.A.T. and Delidakis, C. 2011. Distinct intracellular motifs of Delta mediate its ubiquitylation and activation by Mindbomb1 and Neuralized. J. Cell Biol. 195:1017-1031.

malERA Consultative Group on Vector Control. 2011. A research agenda for malaria eradication: vector control. PLoS Med. 8:e1000401.

Neafsey, D.E., Lawniczak, M.K.N., Park, D.J., Redmond, S.N., Coulibaly, M.B., Traoré, S.F., Sagnon, N., Costantini, C., Johnson, C.,Wiegand, R.C., Collins, F.H., Lander, E.S., Wirth, D.F., Kafatos, F.C., Besansky, N.J., Christophides, G.K. and Muskavitch, M.A.T. 2010. SNP genotyping defines complex gene flow boundaries among African malaria vector mosquitoes. Science 330:514-517.

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. Science 330:88-90.

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. Science 330:86-88.

Artavanis-Tsakonas, S. and Muskavitch, M.A.T. 2010. Notch: the past, the present and the future. Curr. Top. Dev. Biol. 92:1-29.

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.

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.

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 in Drosophila. Genetics 174: 1947–1961.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Press Releases

BC Biologist Marc Muskavitch and Global Team Decode Pathogenome of Virus-Spreading Mosquito
News Release - Virus-spreading mosquito | youtube Video - Virus-spreading mosquito

Boston College Biologist and Team Use High-Resolution Microarray to Advance Malaria Research
News Release - Malaria research | youtube Video - Malaria research