A Giant in His Field

Michael Camilleri, M.D., is a gastroenterologist well-respected by his colleagues for research accomplishments that have led to new treatments for people with digestive disorders. Physician-investigators like Dr. Camillieri see what goes wrong with patients and try to fix it. Problem solving is in their nature. "The needs of the patient come first," Dr. Camilleri states reaffirming Mayo's mantra.

Named a Mayo Clinic Distinguished Investigator in 2007, he's quick to say this is not an accomplishment he reached on his own. Dr. Camilleri credits mentors and scientists who came before him, "giants of the field," he said during an interview from his Rochester office.

Dr. Camilleri is a professor of medicine and physiology. He is a specialist in gastroenterology. He trained at the Royal Postgraduate Medical School in London before coming to Mayo Clinic for a research fellowship (his second) in 1983. Dr. Camilleri has been elected Fellow of the Royal Colleges of Physicians of Edinburgh and London, and named the Atherton and Winifred W. Bean Endowed Professor of Medicine. In 2004, he received clinical investigator status at Mayo Clinic.

It's been nearly a quarter of century since Dr. Camilleri began his research in enteric neurosciencess with a focus on physiology, pathophysiology and the diagnosis and treatment of diseases that affect motility or sensation of the gastrointestinal tract, such as gastroparesis (nerve or muscle damage in the stomach that slows digestion), diabetes, obesity and irritable bowel syndrome.

Q. How would you describe your research in lay terms?

A. I research how food and content moves through the gastrointestinal track and what goes wrong in patients who develop symptoms. I study the function of the gastrointestinal tract as well as its abnormal function in disease states. This includes diabetes, which paralyses the stomach, and carcinoid diarrhea, a condition in which a hormone like serotonin causes significant diarrhea because of a tumor in the body producing the hormone.

I also study how diseases of the nervous system affect the motor function of the GI tract and cause problems with swallowing, digestion and maintenance of bowel continence. More recently we have focused on ways in which the genes we inherit influence the development of these diseases or how they respond to medications. This has the chance to help individualize treatment to increase effectiveness of medications or reduce their side effects.

Q. Your research is all encompassing – from physiology to pathophysiology. In a nutshell you study nutrients, gut hormones, diabetes and obesity, but also the role of genetics in gastrointestinal disorders. You've also been very active in clinical trials for some important treatments – is that correct?

A. At any one time in my laboratory, we're studying two new drugs that are coming from industry so that we can see whether they're worthy of taking to a larger patient population.
In addition, I've been developing and validating tests for motility and sensation disorders in humans that became clinical diagnostic tests at Mayo Clinic and elsewhere. Specifically, the scintigraphic transit (a diagnostic test that produces a two-dimensional picture of food moving through the stomach and intestines), 3D stomach imaging to measure the ability of the stomach to accept food, and manometry (test that measures pressure) and barostat (a device used to measure gut wall tension). In terms of new drugs for motility, we have conducted the first studies of medications and whether they work, how they work and whether they should be developed for approval and marketing or discarded. The medications tested that went on to further drug development include: cisapride, tegaserod, prucalopride, alosetron, neurotrophins, renzapride, lubiprostone, linaclotide, ATI-7505 and a probiotic combination, VSL #3.

Q. Gastro disorders can range from a mild case of irritable bowel syndrome to chronic intestinal pseudoobstruction in which the muscles are paralyzed. Where does your drive come from?

A. From my patients. I see the problems my patients face and the inadequacies of current treatments. That in itself is reason enough to keep addressing the principle goal: To improve the care of our patients.

Q. Mayo Clinic has made some significant contributions to the field of gastroenterology in the last 100 years. Walter Alvarez, Jay Arnold Bargen, Charles Code, Joseph Szurszewski, Keith Kelly, Sidney Phillips, Michael Sarr and Juan Malagelada to name a few. You've trained with some of these scientists, physicians and surgeons or built upon their research. Why is it important to continue this legacy of research?

A. The wonderful Mayo legacy in the science of how the gastrointestinal tract works has been handed down to my generation to translate the scientific information to patient care. I have been fortunate to develop collaborative research in imaging, nerve and muscle measurements and molecular studies to develop diagnostic tests at Mayo Clinic and tools to appraise treatments of diseases like diabetes and obesity in addition to neuromuscular dysfunction of the gastrointestinal tract. Mayo Clinic leads in the clinical application and translation of this science.

Q. What is the Gastroenterology Research Unit?

A. The philosophy of the gastroenterology research unit between 1970 and 1990 has been passed on to several groups in the Division of Gastroenterology and Hepatology: to impact the diagnosis and treatment of significant or common diseases, such as hepatitis, cirrhosis of the liver and common gastrointestinal disorders. Understanding what controls normal function and how it goes wrong in disease is critical to getting it right. The unit's legacy was to apply in the clinic in the afternoon what was learned in the research unit in the morning.

For example, we found that in diabetes, damage to the nervous system affects the way in which the lower part of the stomach is able to break down food and as a result, food is retained in the stomach. With this gastroparesis, we developed approaches to enhance food tolerance, but did so in collaboration with dietitians and medications from the pharmaceutical industry.

In carcinoid diarrhea, we were able to demonstrate that the hormone serotonin induces the very rapid movement of content through the small intestine and colon and how to block it. This led us to appreciate that the same principle applies (albeit at a lower level) in other common conditions, like irritable bowel syndrome with diarrhea. This led to use of alosetron to block the excessive activity of serotonin and reverse the diarrhea and urgency in both conditions.

Q. Has your research led to new treatments for patients?

A. We've been involved in facilitating the development of drugs that block or boost the effects of serotonin (like cisapride (Propulsid) and alosetron (Lotronex)). We have also proved efficacy of a number of medications designed to treat chronic constipation (Lubiprostone (Amitiza)). All these medications were approved for use in clinical practice. Several others that include prucalopride and linaclotide are undergoing tests to determine of they should be approved for use in clinical practice.

Q. Does your research have other goals beyond drug development?

A. Definitely. Many of the investigative methods developed or pioneered in my laboratory have led to validation as clinical diagnostic tests. We've worked to make these tests noninvasive. When people go to a gastroenterologist they think, "Oh my goodness, there's going to be another tube going up or down." But in fact, we can do tests that don't involve tubes. They involve radio-labeling contents in the colon or injections that allow us to visualize the stomach in order to measure how the stomach or the intestines are functioning. Many common illnesses do not involve ulcers, or inflammation or cancers, but they represent problems of function that cannot be diagnosed with conventional X-rays, CT scans, or endoscopy.

The diagnostic tests we developed are applied in the clinic every day, and we use these same measurements to study gastrointestinal functions and the way that nerves, hormones, proteins and the genes that impact on these mechanisms control those functions.

Q. What will your research focus on in the next few years?

A. We're hoping to continue the work we started in obesity and bowel dysfunctions associated with irritable bowel syndrome. One of the greatest things about being at Mayo Clinic is the ability to collaborate across groups. For example, in the field of obesity, I presently have a very fruitful and effective collaboration with colleagues from behavioral psychology to diabetology, surgery, engineering and molecular biology to address ways to improve treatment of obesity. We are studying how variations in certain genes influence the degree of weight loss that can be achieved by treatment with an approved medication, sibutramine. However, we are also working to develop an implantable electrical device that blocks the function of the nerve to the stomach to reduce appetite and increase fullness after meals, thereby resulting in weight loss.

Q. In 19 years, you've mentored 21 research fellows and 29 clinical fellows. What is your hope for the next generation of clinician investigators?

A. I hope that my students will build upon the knowledge and discoveries we've made in understanding the pathophysiology of neuroenteric diseases and that they go on to produce seminal work of their own, so the legacy and support I received from my mentors will be transferred to the next generation. The disorders of gut function require more research and new insights to improve management of these diseases that affect 1 in 4 Americans and account for 40 percent of patients seeking care from a gastroenterologist.. The role of genetics in causing the diseases or optimizing the effects of, medications is a current focus of our group and, in a typical example of what makes translational research more effective at Mayo Clinic, we collaborate with other basic and clinical investigators for greater impact.

We are dedicating ourselves to the effects of disordered gut function, the obesity epidemic, the problems of type II diabetes and the potential role of medical, device and surgical approaches to correct obesity with minimal side effects. These areas require the dedication of young, bright, prepared minds.

Q. In his nominating letter, Dr. Vijay Shah, the associate chair of research for Gastroenterology and Hepatology, described you as a true "Mayo citizen" for your involvement beyond your lab and in leadership roles and mentoring. In fact, in 2002 you received Mayo's Outstanding Mentor Award. You are currently director of Postgraduate education of the Clinical Translational Science Award from NIH, and chair of Conflict of Interest Review Board. How do you balance your time?

A. I enjoy and embrace the diverse challenges and experiences that are available at Mayo Clinic. I have learned to prioritize, compartmentalize and focus on tasks one at a time. More importantly, I have been fortunate to work with a wonderful group of colleagues, physicians, fellows, nurses, administrative, paramedical and educational experts who have brought out the best in me. Mayo Clinic has given me the opportunity to grow personally in ways that I never imagined possible.

Q. How is the Distinguished Investigator award an important point in your career?

A. I'm extremely humbled to have even been considered for such an award. It's gratifying that for someone who spent 20 years dedicated to patient-oriented research and whose program has been more than 95 percent involving direct contact with patients, can also be eligible for this wonderful award. It's the pinnacle of my career at Mayo Clinic.