|
Education:
- Johns
Hopkins University
Ph.D. 1988 Developmental Biology
- Pomona College BA, cum laude 1983 Biology
Academic Positions:
- College
of William and Mary Assoc.
Prof 00-present Biology
Dept
- College
of William and Mary Asst.
Prof. 95-00 Biology Dept.
- University
of Houston Asst. Prof. 91-95 Biology Dept.
- Cornell
University postdoc 88-91 Genetics and Development
 Current
Research: 
Eukaryotic cell division is a highly regulated process during which
cells duplicate their chromosomes, align them in a metaphase plate, and then
segregate these chromosomes equally to each of their two daughter cells. The
transition from metaphase to anaphase is mediated by a specific ubiquitin ligase known as the
anaphase-promoting complex (APC/C) which functions by sequentially targeting
key cellular components for proteolytic
destruction. APC/C activity initiates anaphase by targeting the inhibitor of
a protease that cleaves the "glue" between sister chromatids. In the absence of APC/C activity, mitotically dividing cells arrest in metaphase.
Conversely, premature, unregulated APC/C activity results in chromosome mis-segregation as sister chromatids
separate prior to their proper metaphase alignment. Key questions remain
concerning both the regulation of the APC/C and the function of its
individual sub-units, and my own group is using the powerful molecular and
genetic tools associated with the roundworm Caenorhabditis elegans to
address whether the APC/C has cell-type specific regulators or targets. In
collaboration with the laboratory of Andy Golden (Laboratory of Biochemistry
and Genetics, NIH-NIDDK), we have used APC/C mutants to show that the APC/C
is required not only for the separation of both sister chromatids
during mitosis but also for the separation of paired homologs
during meiosis I (Golden et al., 2000). In current projects, we are seeking
to expand our current understanding of APC/C function and regulation through
the analysis of mutants with similar or identical phenotypes. Ultimately, we
would like to define, in molecular detail, the combination of shared and
unique molecular mechanisms which drive and/or regulate the metaphase to
anaphase transition during the three distinct cellular processes of germline mitosis, oocyte meiosis, and spermatocyte
meiosis. In related studies, we are continuing to use our
temperature-sensitive APC/C mutants as a tool to explore the relationship
between cell cycle progression and development, most recently in the context
of spermatogenesis (Sadler and Shakes, 2000; current studies) and early
embryonic development (Shakes et al., 2003).
Current research
projects include:
- The molecular and genetic characterization of a
novel non-APC gene required for the metaphase to anaphase transition
- The identification and analysis of novel genes
required for proper segregation of chromosomes during meiosis.
- Analysis of the sperm's contributions to early C.
elegans embryogenesis.
- Determining the connection between cell cycle progression
and the process of sperm cell differentiation
- The cellular mechanism of C. elegans
fertilization
Recent
Publications:
- Chatterjee I, Richmond
A, Putiri E, Shakes DC, and Singson A (2005) The Caenorhabditis elegans
spe-38 gene encodes a novel four pass integral membrane protein required
for sperm function at fertilization. Development 132: 2795-2808.
- Frazier T, Shakes D, Hota
U, and Boyd L. (2004) C. elegans UBC-2 functions with the anaphase
promoting complex and has other non-APC related activities. J. Cell
Science 117: 5427-5435.
- Shakes DC, Sadler PL,
Schumacher JM, Abdolrasulnia M, and Golden A (2003) Developmental defects observed in hypomorphic anaphase-promoting complex mutants are
linked to cell cycle abnormalities. Development 130: 1605-1620.
- Davis ES, Wille L,
Chestnut B, Sadler P, Shakes D, and Golden A. (2002) Multiple
subunits of the C. elegans Anaphase Promoting Complex are
required for chromosome segregation during meiosis
I. Genetics 160: 805-813.
- Morton DG, Shakes DC, Nugent S, Dichoso D, Wang W, Golden A, and Kemphues
KJ. (2002) The C. elegans par-5 gene encodes a 14-3-3 protein required for
cellular asymmetry in the early embryo. Developmental Biology 241:
47-58.
- Golden A, Sadler PL,
Wallenfang MR, Schumacher JM, Hamill DR, Bates G, Bowerman B, Seydoux G, and
Shakes DC (2000) Metaphase to anaphase (mat) transition-defective
mutants in Caenorhabditis elegans. Journal of Cell Biology 151(7)
1469-1482.
- Sadler, P.L. and D.C. Shakes. (2000) Anucleate C. elegans sperm can crawl, fertilize oocytes,
and direct anterior-posterior polarization of the 1-cell embryo.
Development 127(2): 355-366.
[Biology Faculty Listings]
[Biology Home Page]
Last updated 5/17/07
College of William
and Mary, Department of Biology
dcshak@wm.edu
|
