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Our laboratory is
interested in the pathophysiological basis and consequences of
inflammation within the gastrointestinal tract. Specifically we
are interested in Inflammatory Bowel Disease (IBD),
colitis-associated colorectal cancer, Irritable Bowel Syndrome
(IBS) and intestinal endometriosis.
The currently accepted etiology for IBD suggests interactions
between the immune system, genetic susceptibility and the
environment. Many therapies are currently available, but there
is still no cure for patients with this disease who suffer from
symptoms including abdominal pain, ulceration, bleeding, weight
loss and diarrhea. Importantly, IBD is linked to an increased
risk of colorectal cancer (CRC) which is a major cause of cancer
death.
IBS is one of the most common disorders encountered by
gastroenterologists, resulting in reduced quality of life and
high economic costs. Several contributory mechanisms have been
suggested including psychosocial factors, altered motility and
abnormal visceral sensory perception, but the underlying
pathophysiology remains unclear.
Endometriosis is a disorder of the female reproductive system,
caused by the presence of benign endometrial implants outside
the uterus (ovaries, fallopian tubes, intestines). Symptoms
often mimic other intestinal disorders leading to misdiagnosis,
and the cause is unknown.
Our laboratory uses a variety of different experimental
techniques, at the whole organ, cellular and molecular level
including: animal models, electrophysiological transport,
motility studies, histological staining and analysis, biological
assay, ELISA, cell culture and molecular biology techniques such
as Real Time PCR and DHPLC.
Research currently underway:
Bacteria and Inflammation
The role of bacteria and their products, such as bacterial
peptides, in the initiation and exacerbation of IBD is still
very unclear. We have been investigating the role of bacteria
and bacterial products in colitis, and whether the ability to
modulate these can influence the progression of the disease. In
IBS we are investigating whether previous inflammation increases
the susceptibility of the colonic epithelium to stress-induced
permeability, enabling endotoxins or peptides of luminal
bacteria to cross, bind to receptors and cause up-regulation of
stimulatory neurons.
 
Inflammation and Motility/Secretion
We are interested in ascertaining the underlying mechanisms
involved in the motility changes associated with IBD, and the
various secretory mechanisms that occur. This is important in
understanding such symptoms as diarrhea. Recently we have been
measuring regional variations in neurokinin receptor subtype
contributions to muscularis mucosae and epithelial function in
the rat colon
 
Stress and Inflammation
There is a great deal of overlap between the symptoms of IBD and
endometriosis, leading to misdiagnosis. We have established a
model of intestinal endometriosis in rats in order to
investigate the differences and similarities between
endometriosis and IBD. We have been studying the role of TNF
receptors, their associated signaling factors and adhesion
molecules. In collaboration with Dr. Idhaliz Flores and Dr.
Kenira Thompson at PSM we are also interested in investigating
the influence of stress on the progression of endometriosis
 
Inflammation and Cancer
Colorectal cancers are the second leading cause of
cancer-related deaths in USA. Patients with long term IBD have a
significantly increased risk of developing colon cancer.
Dysplasia in colitis is preceded by a long history of chronic
inflammation. In collaboration with Dr. Angel Isidro, and Dr.
Jie Wu & Domenico Coppola at the H. Lee Moffitt Cancer Center &
Research Institute, FL, we are investigating the transition of
inflammation to dysplasia and associated genetic mutations, and
the signaling pathways involved.
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