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Stephen Doxsey, Ph.D.
Academic Role: Professor
Faculty Appointment(s) In:
Program in Molecular Medicine
Joint Faculty In:
Biochemistry and Molecular Pharmacology
Other Affiliation(s):
Cell Biology
Cell Dynamics Group
Interdisciplinary Graduate Program
Regulation of Mitotic Spindle Assembly
 Microtubules are required for such fundamental cellular processes as cell
division, embryogenesis, cell motility and organelle translocation. In all animal cells, the
microtubule cytoskeleton arises from the centrosome, an organelle with the ability to nucleate
microtubules.
This laboratory is interested in understanding how the centrosome organizes microtubule arrays
such as the mitotic spindle. We have cloned and characterized pericentrin, a highly conserved
centrosome protein essential for cell division and microtubule organization. Pericentrin
forms a large complex with gamma tubulin and other proteins involved in microtubule
nucleation. Expression of mutated forms of pericentrin in cells induces the formation of
'ectopic centrosomes' that nucleate microtubules. Current work involves expression of chimeras
of pericentrin and green fluorescent protein to monitor centrosome dynamics and function in
living cells. In collaboration with the Biomedical Imaging Group, who developed new
superresolution immunofluorescence technology, we discovered that centrosomes are comprised of
a novel lattice structure (see Figure A). The mechanism and regulation of centrosome assembly
is being investigated using in vitro reconstitution systems and in vivo systems developed in
our laboratory. Centrosome assembly in mammalian cells is microtubule-dependent and mediated
by the molecular motor, dynein. We are characterizing other highly conserved, novel centrosome
proteins identified with serum from patients with the autoimmune disease, scleroderma.
Finally, we recently discovered that pericentrin is overexpressed in tumors and that tumor
cells have abnormal centrosomes, suggesting a possible role of pericentrin in
tumorigenesis.
Office: Biotech II-Suite 210
Phone: 508-856-1613
E-mail: Stephen.Doxsey@umassmed.edu
Keywords:
Cancer Biology,
Cell Biology,
Biochemistry
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55 Lake Avenue North Worcester, MA 01655