Caroline B. Appleyard, PhD

Professor

Department of Physiology and Pharmacology

 

Research Info

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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