Ph.D., Stanford University
Tel: (617) 552-2717
E-mail: marc.muskavitch@bc.edu
Fields of Interest
Molecular cell biology of Notch signaling during development. Molecular
cell biology of host-pathogen interactions in vector insects.
Academic Profile
Molecular cell biology of Notch signaling during development.
The Notch signal transduction pathway functions in most developmental decisions
that occur during metazoan development. In some contexts, this signaling preserves
the pluripotence of cells, leading to cell type diversity within complex tissues.
In other contexts, this signaling induces adoption of particular cell fates.
Aberrant Notch signaling has been implicated in oncogenesis in humans. For some
time, we have focused on the genetic and cell biological analysis of the function
of Delta, a ligand, and Notch, the receptor, in this pathway. The recent work
of our group and others has revealed that subcellular trafficking (including
endocytosis) and post-translational modification (including ubiquitination)
of Delta, Notch, and proteins with which they interact, are crucial for activation
and inactivation of Notch pathway ligands and receptors. We are employing genetic
screens, molecular genetics, and cell biological analyses to further elucidate
the molecular mechanisms that underlie Notch pathway function. Given the implication
of aberrant Notch signaling in oncogenesis, we want to understand the roles
of endocytic machinery components in normal and aberrant Notch signaling, and
to identify small molecules that could interfere with aberrant signaling and
might function as anti-cancer therapeutics. Given the implication of Presenilin
(Psn) activity in Notch activation and in Alzheimer’s Disease, we want
to understand the roles of endocytic machinery components in Psn-dependent activation
of Notch. Given the implication of Notch activity in the normal development
of pluripotent cell lineages, we want to determine whether regulated activation
of Notch signaling can contribute to the development of pluripotent stem cell
lines.
Molecular cell biology of host-pathogen interactions in vector insects.
Anopheline mosquitos (e.g., Anopheles gambiae) and Culicine mosquitos
(e.g., Aedes aegypti) serve as vectors for diseases that affect hundreds
of millions of people each year. We are employing bioinformatics analysis to
identify and further characterize putative secreted and membrane-resident proteins
(SMRPs) and components of the endocytic trafficking machinery (ETM) in An.
gambiae, the primary vector of human malaria in Africa, and Plasmodium
falciparum, the most virulent species among human malaria parasites. We
intend to combine functional genomics and chemical biological techniques to
identify proteins among the SMRPs and the ETM that are required for successful
host-pathogen interactions that underlie malaria transmission. We will then
identify small molecules that disrupt these interactions, and hope to employ
some of these leads as starting points for development of treatments that will
contribute to reductions in the morbidity and mortality associated with malaria
in humans. Along similar lines, we are using bioinformatic approaches to identify
components of the ETM in Ae. aegypti, the primary vector of dengue
fever virus. We will employ comparative genomics and chemical biological techniques
to identify small molecules that interact specifically with ETM components required
for dengue virus transmission, and hope to employ some of these leads as starting
points for development of treatments that will contribute to reductions in the
morbidity and mortality associated with dengue fever and dengue hemorhaggic
fever in humans.
Representative Publications
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 [Epub ahead of print]. (link to 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. (link to 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. (link to 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. (link to 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. (link to 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.
(link to PubMed abstract)
Jacobsen, T.L., Brennan, K., Martinez Arias, A., and Muskavitch, M.A.T. 1998.
Cis-interactions between Delta and Notch modulate neurogenic signalling in Drosophila.
Development
125: 4531–4540. (link to 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. (link to 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. (link to 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. (link to 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. (link to PubMed abstract)
| Return to Faculty List | Biology Home | Graduate Studies |