Too much of a good thing

By Dennis Gilbert
College of Pharmacy

For 20 years, Lynda Welage's clinical practice has brought her face-to-face with some of the most seriously ill patients at U-M Hospital: patients suffering from burn, trauma, and other critical illnesses.

Managing the care of such patients is invariably complicated, with little to no margin for error.

As a clinical pharmacist in the Trauma Burn Center of the University Hospital, one of the most common complications she encounters is the body's natural tendency to react to trauma with an aggressive inflammatory response.

“Under normal circumstances, inflammatory response is beneficial in neutralizing invading infectious microorganisms,” says Welage, who is a professor of clinical sciences and associate dean for academic affairs in the College of Pharmacy. “But an overwhelming systemic inflammatory response in acutely ill patients can create a host of problems, including sepsis, renal failure, and acute respiratory failure, to name a few.”

If acute inflammatory response reaches the gastrointestinal tract, the result can be devastating. First, the GI tract plays an important role in the body's immune function, and without a robust immune system, the body cannot fend off infection. Secondly, alterations in gut integrity due to the inflammatory response can lead to alterations in the absorption of drugs and nutrients.

The question Welage is trying to answer in her research is what effect, if any, does acute inflammation have on intestinal transporters — those proteins in the epithelial membrane of the intestines that carry nutrients and drugs across the intestinal membrane barrier, into the blood stream.

“If we understand more about what causes the alteration in the intestinal membrane barrier — not just from a drug standpoint, but also the mechanism, which is another part of my research — then we can develop strategies to improve barrier function; improve nutrient absorption; improve drug absorption,” Welage says.

The College of Pharmacy's multidisciplinary Center for Molecular Drug Targeting (CMDT) and the Clinical Pharmacogenomics Laboratory (CPL) provide a leap forward in her search for answers to these and other translational research questions.

“Modern research has become far too complex and expensive for any one person o small group to go it alone and make much headway,” Welage says. “What the CMDT and the CPL offer are thematic approaches to research. By bringing an interdisciplinary team of clinical and basic science research minds to bear on specific questions, we are better able to arrive at more complete solutions.”

“The CMDT and CPL also offer a more efficient use of personnel and equipment resources,” Welage adds. “By pooling resources as well as expertise, we all gain access to more cutting-edge equipment that will allow all of us — and each of us — to compete more effectively for research dollars.”