Daren Knoell Leads the Way for Zinc Research
Daren Knoell, a full professor in the College of Pharmacy and College of Medicine, has been an independent thinker since forging a unique path after receiving his Doctor of Pharmacy degree from the University of Nebraska. Instead of following classmates into industry or clinical practice, Knoell decided to pursue bench science by completing a year of clinical residency training followed by 3.5 years of postdoctoral fellowship training at the University of California at San Francisco (UCSF).
"Bench science was always a passion and groomed me to be an academician. Plus, I always wanted to be an instructor," says Knoell.
Knoell is a founding member of FIC and continues to be a highly active and dedicated member, including his interdisciplinary research on zinc and its influence on sepsis, obesity, and immune function. Zinc deficiency is fairly common in the United States, but individuals who are deficient typically do not appear any different from those with a normal amount of zinc. Only a blood test can reveal zinc deficiency and even that test is not always highly accurate in determining zinc status, particularly when other serious medical conditions exist.
A healthy level of zinc is maintained through eating a well-balanced diet. Zinc is common in protein food sources such as meat, oysters, crab, and peanuts to name a few. For most of us, maintaining proper zinc balance is not difficult to do but can be when access to proper food sources is limited.
Knoell explains that healthy zinc levels are most difficult to maintain in developing countries due to grain-based diets. A grain-based diet does not contain high amounts of zinc and is further complicated by high concentrations of phytates that block the absorption of zinc into the bloodstream, increasing the risk of infection. This problem can be solved by providing supplementary zinc at a cost of just pennies a day, but the task is not as simple as it may seem.
A primary focus of the Knoell laboratory is to study the influence of zinc and its metabolism in the setting of sepsis. Septic patients in the United States are particularly vulnerable to acquiring zinc deficiency because of preexisting co-morbid conditions. Currently, the consequences of zinc deficiency incidences in this patient population are under-appreciated and also very difficult to study.
In published studies that utilized an animal model of sepsis, Knoell and colleagues revealed the significant impact of zinc deficiency on the survival in septic mice. Zinc deficient but otherwise healthy adult mice exhibited 90% mortality in response to sepsis. Mice given a normal diet had only 30% mortality. Using this model and human observational studies they have gone on to reveal that zinc, or a lack thereof, has profound influence on molecules involved in regulating immune function and host defense.
In the future, Knoell and his colleagues hope to translate their observations into innovative and meaningful diagnostics or prognostics that help determine whether septic patients need zinc supplementation to improve outcomes.
Recent results from the Knoell laboratory have revealed a critical zinc transporter in the body that is triggered by "danger signals" following infection or inflammatory stimuli. Capitalizing on this finding, his group was able to establish what is believed to be a novel connection between zinc and obesity. Chronically obese patients also commonly suffer from chronic inflammation leading to an increased risk of developing cardiovascular and pulmonary disease. In their FIC-funded study "Zinc Deficiency Enhances Chronic Inflammation in Obesity," mice fed a combined high fat and low zinc diet experience increased inflammation compared to mice that consume normal or just high fat diets. Importantly, a lack of zinc alters the body's ability to tolerate obesity and leads to a corresponding increase in systemic inflammation.
Transitioning the fundamental discoveries of zinc and immune function into a focus on obesity is difficult.
"It becomes a challenge because it is at first like learning a new language," says Knoell.
Fortunately the talented and diverse team of FIC researchers that Knoell assembled helped to navigate the discipline-specific jargon, leading to improvements in their study design.
"Every collaborator had a fundamental role and provided insight in accomplishing aspects of the project that otherwise could not have been done."
It was this cohesive collaboration that earned Knoell and his team a 2010 Innovation Incentive Award and a 2011 Seed Grant from the Food Innovation Center.
"It is remarkable how the FIC brings together a very diverse campus. FIC continues to grow and really speaks to the spirit of our university," says Knoell.
Knoell is a first-generation college graduate from the University of Nebraska with a Doctor of Pharmacy. He was appointed Assistant Professor at The Ohio State University in 1994. Currently he is a full professor in College of Pharmacy and Medicine as is a member of the Dorothy M. Davis Heart and Lung Research Institute. He also continues to serve on the Faculty Grant Proposal Review Committees for the Food Innovation Center.
Written by Chau-Sa Dang
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