Beyond Basic at the Stowers Institute for Medical Research

Investigating fundamental processes underlying health and disease with a commitment to training the biomedical workforce.

Stories of breakthrough medical discoveries often evoke a sense of linearity, whereby fundamental discoveries are connected to new treatments or cures for patients by a straight line. In many cases, however, the path to discovery is more like a circle linking patients, physicians, and scientists together in a continuous feedback loop.

The Stowers Institute for Medical Research plays an important role in this dynamic process, with its commitment to basic biomedical research, education, and training.

The Stowers Institute emerged on the scientific scene in 1994, when the late James “Jim” E. Stowers Jr., the founder of American Century Investments, and his wife Virginia G. Stowers, established the Institute, dedicating their personal fortune to improving human health through basic research.

Over the years, the Stowers Institute’s unique philosophy and environment, which fosters interdisciplinary collaboration and encourages outside-the-box thinking, has been the driving force behind promising insights and discoveries that have advanced our understanding of health and disease.

“The nature of science is that you just don’t know what the next discovery’s going to be, and I think the most exciting opportunities for discovery and innovation are from that interface between people who have different backgrounds,” says Betty Drees, MD, FACP, FACE, president of Stowers Graduate School and Dean Emerita of the University of Missouri-Kansas City (UMKC) School of Medicine. “Having an institution like Stowers in this community just provides another spark towards that innovation and creativity and discovery.”

A Unique Space for Basic Research

The Institute’s 600,000-square-foot research facility, situated on the former campus of the Menorah Medical Center in Kansas City, Missouri, was designed to provide state-of-the-art laboratory space, equipment, and technical support, and to encourage collaboration between scientists. The first laboratories opened in 2000. In 2009, the Institute added a 280,000-square-foot complex in South Kansas City to accommodate additional support functions and storage facilities.

On a typical day, about 500 Stowers members, most of them scientists, fill the Institute’s labs and halls—sharing ideas over coffee, meeting with colleagues from other institutions at seminars and symposia, and passing on their knowledge to students. Together, they work on more than 150 ongoing research projects, many of which fall into the general research areas of chromatin and gene expression regulation, chromosome structure and cell division, developmental neuroscience, stem cell biology and regeneration, and computational biology and biomathematics. At a place where crossover is encouraged, most of the 22 Stowers laboratories headed by principal investigators (PIs) conduct research in multiple areas.

The Stowers Institute for Medical Research in Kansas City, Missouri.

In addition to PI labs, the Institute has 16 scientific support teams, comprising more than 100 highly-trained scientists, to give researchers easy access to scientific infrastructure, technology and expertise—from unusual model organisms such as cavefish and the starlet sea anemone to sophisticated gene sequencing technology. Having these resources and expertise at their disposal saves researchers precious time they can reinvest in their work. In addition, Stowers research is largely supported by an endowment established initially by Jim and Virginia Stowers. This type of endowment funding allows Stowers researchers to focus more energy on scientific research rather than grant-writing efforts to secure their own funding.

Training Future Scientists

Education is an important part of the Stowers Institute mission. The Institute launched a graduate training program in the fall of 2011, and offers a summer research program for undergraduate students as well as a postdoctoral training program. Over the last decade, the Institute has trained hundreds of undergraduate, predoctoral, and postdoctoral researchers for scientific careers.

The Graduate School of the Stowers Institute for Medical Research provides a rigorous research program that emphasizes critical thinking combined with in-depth experience in the latest methodologies. The competitive program, which offers a PhD in Biology, enrolls an average of eight predoctoral researchers each year. Graduates of the program have gone on to take biomedical research positions at places such as Genentech, the University of Oregon, and Washington University in St. Louis. The Institute also offers PhD training in affiliation with graduate programs at several other research institutions.

The Institute’s postdoctoral researchers collaborate with Stowers investigators and scientific support teams to gain the skills and credentials they need to launch independent research careers. Stowers postdocs can take advantage of outstanding interdisciplinary expertise and opportunities to learn new techniques to expand and accelerate their own research.

The Stowers Summer Scholars Program offers undergraduate students pursuing a degree in the biological and physical sciences, as well as recent graduates, the opportunity to immerse themselves in a research topic over the summer. The eight-week program accepts about 30 Scholars each year.

From Bench to Bedside

In addition to researchers in PhD programs, students from local MD-PhD programs as well as practicing physicians have performed research in Stowers labs. These opportunities provide clinically-focused trainees and healthcare providers exposure to the more basic side of biomedical research.

Wanting to delve deeper into the mechanisms of cancer, Erin Guest, MD, now an associate professor in the Department of Pediatrics at the University of Missouri-Kansas City and Children’s Mercy Hospital in Kansas City, Missouri, trained in the Shilatifard Lab at Stowers (now at Northwestern University Feinberg School of Medicine) in 2009. She worked there while a hematology/oncology fellow at Children’s Mercy, with support from a young investigator award from Alex’s Lemonade Stand Foundation.

For the next three years, Guest juggled seeing patients in the hospital clinic once a week and attending educational conferences and meetings, with four days immersed in the lab. Having “absolutely no prior lab experience,” Guest relished the hands-on experience in basic bench techniques and learning about the Mixed Lineage Leukemia (MLL) gene. Chromosomal breaks in the gene can cause an aggressive form of leukemia. Guest studied how it functioned, what proteins it made, and what causes it to break.

Guest remembers a patient she treated with an MLL gene break – a four-month old baby who initially responded well to treatment, but ultimately didn’t survive.

“Her mother, during one of the last times I said goodbye to her, said, ‘I just want you to take my child’s blood, take it to Stowers and do research on it.’ That to me was really meaningful and inspirational,” she says.

The conversation spurred Guest to establish a biorepository at Children’s Mercy to bank patient samples of blood, leftover tumor samples, DNA, and clinical data, and be open to research scientists. Guest has sent samples from more than 100 patients to Stowers scientists Linheng Li, PhD, and John Perry, PhD, (formerly a Li Lab postdoc, now at Children’s Mercy Hospital), for their research on cancer stem cells. She also runs a National Cancer Institute-sponsored clinical trial studying a new drug for infants with the MLL gene break.

The busy pediatric oncologist says she frequently draws on her Stowers training to conduct research of her own and to make educated treatment decisions.

“Every single cancer is different, and for each patient an oncologist has to look and find out what’s to know about the disease, and what’s known about the genomics of the disease and assess different treatments,” she says. “Then we give families possible options. For me, having that basic science exposure helps me search the literature, read it, and understand it with more of that scientific mindset.”

Learning Collaborative Science

Kristin Melton, MD, associate professor in the Department of Pediatrics at the University of Cincinnati, was a practicing neonatologist at Children’s Mercy Hospital when she secured a spot in the lab of Paul Trainor, PhD, who studies neural crest cell development and its relationship to craniofacial, heart, and gastrointestinal birth defects and disorders. His work aligned closely with the problems Melton saw in her patients on a day to-day basis.

“During development, many organs are developing together at the same time,” she says. “When we see newborns with problems, we’ll see, for example, that they have craniofacial abnormalities, and abnormalities of their hands, or abnormalities of their kidneys, or other areas. Understanding how those organs develop together was really helpful and interesting.”

Melton conducted research in the Trainor Lab from 2001 to 2007, supported for three of those years by a National Cancer Institute K08 fellowship, which provides funding and protected time to early career clinician scientists. She typically worked three weeks in the hospital caring for newborns and babies and spent the fourth week doing research.

While in the Trainor Lab, Melton worked with many tools and techniques that were innovative at the time, such as using microarrays to identify genes important to craniofacial development and developing a mutagenesis screen in mice to identify novel genes in early craniofacial development.

“It was very productive time,” Melton says. “We identified and evaluated about 10 different genes.”

Now, with her Stowers training behind her, Melton works as a neonatologist at Cincinnati Children’s Hospital Medical Center, where she helps direct the hospital’s neonatal-perinatal fellowship. While she’s no longer conducting basic research, she says her time in the lab taught her the essentials behind great science.

“I learned how collaborative science works,” she says. “I worked with many different people and learned from different methods, and from people who were working in fields that were very different from my own. At Stowers, there’s a lot of sharing and collaboration going on that helps you build your science. I think it’s a great model.”

A Diversity of Ideas

The Stowers Institute also benefits from the perspectives physicians and budding scientists bring to its labs—whether it’s a fresh take on a thorny research problem or first-hand experience treating patients with a disease or developmental process that’s being studied.

The Stowers Institute for Medical Research houses more than 20 independent research programs and 16 scientific support teams.

For his part, Trainor says his lab has prospered from relationships with visiting physicians and students in training. Melton, for example, shared how developmental disorders affect the tiniest patients.

“I don’t see human patients, and I’m not responsible for diagnosing or treating them,” Trainor says. “So any time you have someone that comes into the lab with a completely different experience, it is incredibly enriching for any of the projects we do. And that’s true of any type of research collaboration that you undertake. Different perspectives lead to diversity of opinions and a diversity of ideas.”

The Trainor Lab has been working on Treacher Collins syndrome, a developmental disorder that is characterized by malformation of the ears, eyelids, cheekbones, and jawbones. The condition recently rose to prominence with the book and movie Wonder, where the main character has Treacher Collins syndrome. Children with the condition often face years of reconstructive surgery that is never fully corrective. The Trainor Lab is investigating the roles of the TCOF1, POLR1C and POLR1D genes in neural crest cell development as a mechanism for understanding the origin of the birth defect and how to prevent and repair it.

Trainor and his team often attend retreats for individuals with Treacher Collins syndrome and their families. Listening to families share their stories and day-to-day challenges motivates the team to do their best research. The team also educates families about their latest findings and explains the genetics behind the disorder.

“We’ve come to really understand and appreciate that one of the most critical things for affected individuals and their families is just a much deeper understanding of why the condition occurs and how it occurs,” Trainor says. “Parents often feel incredibly guilty if they have a child who’s born with a developmental difference, and it’s very natural for them to blame themselves. But, the more knowledge they have about how the condition occurs, the more it helps them realize that it wasn’t their fault.”

For Trainor, this kind of back-and-forth discussion is a form of translational medicine, though not in the traditional sense.

“Sometimes people think about translational medicine purely in a clinical treatment sense, but I think it is much, much broader than that, and it can involve simply the communication of new knowledge to people that matter – the patients,” Trainor says.

Why Basic Research Matters

Looking to the future, the Stowers Institute will continue to support and conduct basic research, strive to enable innovative approaches to improve human health, and educate and train researchers in preparation for scientific, biomedical, and related professions. Studying fundamental questions about biology, health, and disease with a broad, long-term perspective yields data and discoveries that are the stepping stones for future medical advances. Many times, these outcomes are completely unpredicted at the outset of the research, yet history shows they happen on a regular basis.

“There are many examples of basic science discoveries that are essential to our understanding of clinical medicine, such as how cholesterol is metabolized, or blood clots, or cells become cancerous,” Drees says. “You can’t practice medicine without understanding basic science.”