| 285 | Bruce M. Boman, MD, PhD, MS, FACP | <p>​​​<br></p> | 302-623-4540 | | brboman@udel.edu | Center for Translational Cancer Research, The Helen F. Graham Cancer Center and Research Institute, Christiana Care Hospital | Center for Translational Cancer Research, The Helen F. Graham Cancer Center and Research Institute, Christiana Care Hospital | | | <ul><li>BISC 625 - Cancer Biology (guest lecturer)</li><li>
CHEG 660 Systems Biology (guest lecturer)<br></li></ul> | <p>The main focus of my laboratory research is to understand molecular
mechanisms that mediate development of colorectal cancer (CRC). CRC is
the second-leading cause of cancer deaths both in the US and worldwide.
The goal is to identify mechanisms that will lead to the development of
new more effective, potentially even curative or preventive, treatments
for colon cancer.</p><p>I have over 20 years’ experience as a laboratory chief investigating
the molecular and cellular etiology of colon cancer. I am also a
clinical investigator and have been integrally involved in translational
efforts at all levels to advance the discoveries of cancer research to
the benefit of oncology patients. In addition, I have made numerous
contributions to the field through publications (>150),
presentations, as a patient advocate, and service as a member on many
NIH committees and study sections.<br></p> | <p><span style="text-decoration:underline;">Cancer Stem Cells</span>. Based on the emerging paradigm in oncology,
effective agents will need to target cancer stem cells because
malignant stem cells become overpopulated within tumors that drives
cancer growth. Our recent research findings led to the discovery that
aldehyde dehydrogenase (ALDH) is a specific marker for colonic stem
cells and allows tracking of stem cell overpopulation during colon
cancer development. Additionally, we showed that stem cell
overproduction results from increased symmetric stem cell division. The
test for ALDH also gives us the technology to isolate cancer stem cells
from colon cancers. Our lead scientific paper that reported this finding
was published in the most widely distributed cancer journal in the
world, Cancer Research, and it has been widely cited (over 400 times) in
the scientific literature. </p><p>
<span style="text-decoration:underline;">APC Tumor Suppressor Gene</span>. My laboratory also investigates the
adenomatous polyposis coli (APC) gene which is the most common (~90%)
occurring mutation in colorectal cancers. Several lines of scientific
evidence demonstrate that APC mutations. We were the first research team
to report that mutation in the APC gene leads to stem cell
overpopulation during colon tumorigenesis. Unfortunately, we do not
currently have any systemic drugs that target APC or colon cancer stem
cells. Thus, our translational research goal is to design novel agents
that target APC in order to develop cancer stem cell-based treatments
for cancer patients.</p><p>Our further studies focused on the specific molecular mechanisms that
become dysregulated in cancer cells due to APC mutation. We showed that
the APC protein acts, via a gene transcription factor (TCF4), to
normally down-regulate expression of survivin which is a protein that
functions to prevent cells from undergoing programmed cell death.
However, when APC becomes mutant, this leads to increased expression of
survivin in colon tumor cells and protects them from being killed by
cancer drugs. We also showed that survivin expression is upregulated in
APC mutant mice in association with Tcf4 activation and intestinal
tumorigenesis. </p><p>
<span style="text-decoration:underline;">HOX Genes</span>. HOX genes encode an evolutionarily conserved set of
transcription factors that control how the phenotype of an organism
becomes organized during development based on its genetic makeup. For
example, in bilaterian-type animals, HOX genes are organized in gene
clusters that encode anatomic segment identity, that is, whether the
embryo will form with bilateral symmetry with a head (anterior), tail
(posterior), back (dorsal), and belly (ventral). Although HOX genes are
known to regulate stem cell (SC) differentiation and HOX genes are
dysregulated in cancer, the mechanisms by which dysregulation of HOX
genes in stem cells causes cancer development is not fully understood.
Hence, we have been studying how dysregulation of HOX expression
contributes to CRC development.</p><p><span style="text-decoration:underline;">Retinoid acid signaling</span>. Because aberrant dysregulation acid
(RA) signaling alters cell proliferation and differentiation that might
contribute to CRC progression and because ALDH is a key enzyme in the RA
signaling pathway, we are studying RA signaling in normal and malignant
colon stem cells. RA signaling is mediated by two nuclear retinoic
receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X
receptor (RXR). We discovered that retinoid receptors RXR and RAR are
selectively expressed in ALDH+ stem cells, which indicates RA signaling
mainly occurs via ALDH+ stem cells, which provides a mechanism to
selectively target cancer stem cells. Our goal is to determine how RA
signaling regulates stem cell dynamics and how to translate research
findings to CRC initiation and progression.<br></p> | | | | | | |
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