It was a lonely first day at work for Nathan Qi, M.D., Ph.D., on March 1, 2006, as the one and only researcher at the new Animal Phenotyping Core (APC) lab. He didn’t have a technician, he didn’t have a lab to work in, he didn’t even have one mouse.
Now, 15 years later, the 3,000-foot lab is among the top five mouse metabolic phenotyping centers in the country. With a $6 million NIH grant fulfilled and more in progress, Qi’s team of six also finds time to conduct hundreds of individual experiments every year, while supporting more than 50 U-M laboratories and another 20 external institutions.
That success has been built on a foundation of integrity — one of Michigan Medicine’s five core values.
Starting small — with big dreams
Qi was hired to build the APC from the ground up and that is exactly what he did.
“Unfortunately, my lab was not ready at that time so I stayed in the old Kresge building for a couple of months,” he said. “I made a list of stuff I needed, talked to principal investigators (PIs) working on key studies, and conducted a campus survey to find out what animal phenotyping services were most needed. I accepted one small experiment that I could handle myself at a time while looking to hire a technician.”
The APC primarily conducts studies on mice to test blood sugar levels, insulin sensitivity, and energy metabolism. The end goal is to learn more about human diseases, such as obesity, type 2 diabetes, and their related complications.
The team does this through rodent phenotyping, a process that determines, analyzes or predicts the animal’s traits and how they are influenced by genetics or changes in the environment.
The importance of integrity
Qi and his team believe their research is vital not just to making discoveries but for setting an example of how such work should be carried out.
Indeed, the team works to teach established investigators, postdoctoral fellows, and students at Michigan Medicine how their phenotyping animal research complements related human studies. And they do so by becoming role models with the highest ethical standards in all their work.
“We continually review our experimental work to reflect the ideals of rigor and reproducibility. We supply our customers detailed information about the procedures and comprehensive data analysis,” Qi said.
Integrity is equally important when working with the animals.
“It is our moral obligation to respect all living beings, so we adhere to the highest ethical and scientific standards when conducting these experiments to maintain the animals’ well-being,” he said. “All animals receive nutritional food and drinking water and have access to social and behavioral enrichments, such as appropriate companions, soft bedding, and novel objects for exploration. Surgical procedures are performed under sterile conditions with general anesthesia and appropriate analgesics, with the understanding that procedures that cause pain or distress in humans may do the same in rodents. We also vigorously work to reduce animal use by providing one-stop-shop services to our customers through collaborations with other laboratory services on the campus.”
Keeping costs down
With those priorities in mind, Qi’s team has set lofty ambitions for their research. And with those goals come a number of challenges, not the least of which is cost.
The lab was initially established with financial support from the Michigan Metabolism and Obesity Center and the Michigan Diabetes Research Center, but to sustain itself it needed to draw in national grants and wealthy customers — such as pharmaceutical companies — to support their sophisticated work and costly equipment.
Again leaning on integrity, keeping prices as low as possible was important to Qi, who felt it was the key mission of the lab to provide phenotype services to U-M researchers at a reasonable price.
“This work can be sophisticated and challenging, requiring specific laboratory skills and expertise, laboratory tools and equipment, standardized methodology, and administrative regulations,” Qi said. “Many laboratories don’t have the capacity to complete such experiments, which are frequently required by grants or publications.”
“We wanted to develop a core that would be nationally recognizable by providing professional and high-quality services, having NIH grants, and through reputations via collaborations and publications. Our hope was to bring in more revenue so we could actually lower the costs for our faculty and students on the campus.”
Building reputation through breakthrough research
It didn’t take long for the team to reach more milestones than they even imagined. Their first major breakthrough came when they became one of the few institutions across the country to conduct rigorous insulin clamp studies which revealed how obesity, high-fat diets, and specific gene mutations lead to the development and progression of diabetes. These gold standard studies now lead scientists to the discovery and testing of novel drug treatments.
Then, in 2016, the lab successfully acquired the $6 million NIH grant under the leadership of Malcolm Low, M.D., Ph.D., the David F. Bohr Collegiate Professor of Physiology and director of the center. The grant allowed the APC to gain substantial expertise in the microvascular complications of diabetes and the influence of intestinal bacteria on digestive function and host metabolism. Soon, the team was expanding its services to numerous academic institutions around the U.S. and Europe.
The lab has not slowed down since, not even for COVID-19. As one of the few basic science research labs to remain active during the shutdown, the team not only continued working on experiments for research on campus, they also tested an oral form of the COVID-19 vaccine in mice for a biotech company.
Much more on the horizon
Work continues at the lab, both directly by the team itself and in support of others at the university and external institutions. For example, Daniel Wahl, M.D., Ph.D., assistant professor of radiation oncology, received external grants to study tumor metabolism with the aim to generate novel treatments and/or diagnostics. The APC collaborates with his lab by conducting complex studies necessary to complete Wahl’s work.
In addition, Qi has just begun three new projects studying muscular dysfunction, insulin resistance and diabetes, and acute pancreatitis.
Visit the Animal Phenotyping Core website for more information about the lab.
Pictured from left-to-right in the above photo: Zhe Wu, Jiane Feng, Lauren Benson, Eric Westfall, Kristina Metz, Nathan Qi, M.D., Ph.D. Not pictured: Malcolm Low, M.D., Ph.D.