BS (2002, University
of St. Francis, Fort
Wayne, IN), Ph.D. 2007,
University of Notre Dame, Notre Dame IN)
Previous
experiments in the laboratory have established that transcription of the cyclin kinase inhibitor p21 gene is induced following
stress as a result of binding of p53 to defined
response elements within the gene. To dissect the temporal aspects of the
formation of the transcriptional complexes Jamie has constructed a 6 kb composite
reporter gene encompassing the proximal and distal elements of the p21 promoter.
He is performing sequential ChIP-ChIP analysis to
determine if a temporally ordered occupancy of the response elements is
required for the assembly of functional RNA Pol II
complex on the basal promoter. In addition he is investigating whether the same
temporal sequence is seen with different cellular stresses or chemotherapies.
Graduate Students:
Sarah Mordan-McCombs, BA (2003, DePauw
University, Greencastle, IN)
To investigate the role of the
vitamin D receptor in prostate carcinogenesis, Sarah has crossed the Vitamin D
receptor knockout mouse (VDRKO) with the LBP-Tag mouse which predictably
develops prostate cancer. Using a variety of methods including histological
analysis and molecular techniques she has examined the role of calcium and
androgens in the progression of prostate cancer. She is currently using laser
capture micro-dissection (LCM) and gene array technologies to define the role
of the VDR in the epithelial-stromal
interactions responsible for the growth regulation of prostate tumor growth and
progression.
Namita Chatterjee, BSc (2003, University of Waterloo,
Waterloo, ON Canada), MS (2008, University of Notre
Dame, Notre Dame IN)
Namita is establishing new
pre-clinical models to study inflammatory breast cancer (IBC). IBC is a rare
but very aggressive form of breast cancer that has a very different natural
history than more common ductal carcinoma in situ
(DCIS). Development of new therapies for IBC have been
hampered by the lack of good model systems for the disease. Using two
inflammatory breast cancer cell lines (SUM-149PT and SUM-190PT), originally
established at the University of Michigan, Namita is characterizing their
growth response to estrogen and their response to anti-estrogens and histone deacetylase inhibitors in
vitro and in orthotopic models of breast cancer. The
objective of these studies is to develop a better understanding of the cell and
molecular biology of IBC and to develop improved therapies for IBC.
Winnie Wei-Lin Wang, BSc (2007,
Queen’s University, Kingston
ON Canada)
Winnie is using whole genome
transcriptome analysis, real time PCR and Western blotting to investigate the interaction between
vitamin D receptor-mediated signaling and androgen receptor-mediated
transcription in prostate cancer. Her observations have established that
elevated levels of vitamin D may abrogate the effects of anti-androgens such as
bicalutamide in prostate cancer, particularly in men
with normal circulating androgen levels. Her results implicate several vitamin
D-responsive, calcium-mediated processes in the modulation of cell death in
prostate cancer cell lines. She is using in vitro models of early stage and
locally invasive prostate cancer to characterize the involvement of the vitamin
D endocrine system in the efficacy of standard hormone therapy.
Visiting Co-op Students
Ann-Christin Gaupel, Diploma Thesis, Department of
Chemistry and Biochemistry, University
of Bielefeld, Bielefeld, Germany
Ann-Christin is using
two-dimensional gel electrophoresis and mass spectrometry to examine the
effects of several histone deacetylase
inhibitors on the acetylation of nuclear proteins in
general, and p53 in particular. Previous studies in the laboratory have
established that post-translational modifications of p53, particularly acetylation, play a critical role in stabilizing the
protein, but also result in the formation of different transcriptional
complexes in prostate and breast cancer cell lines depending on the site of acetylation and the other modifications present in the
protein. Since there are many other targets for acetylation
and deacetylation in the nucleus besides p53,
Ann-Christin is also using twodimensional
fluorescence difference gel electrophoresis (DIGE) to identify changes in the
post-translational modification of other nuclear proteins.
Summer Students
Courtney Ensslin undergraduate major in Biological Sciences,
University of Notre Dame, Notre Dame IN
Technician
Ken Jones
