Institute for Translational Medicine

Most nurses feel as though research is something that they simply don’t have time for, given the nature of their jobs.

“I’d love to participate in nursing research more, but our jobs are so task-oriented,” said Bethany Rettberg, RN, BSN. “I come in, check my email, respond to what’s urgent, and get to work caring for my patients.”

But the key point of the 2012 Nursing Research and Evidence-Based Practice Symposium, held on April 27, at the Gwen and Jules Knapp Center for Biomedical Discovery at the University of Chicago, was that nurses can — and should — play a big part in research, right at the patient’s bedside.

The symposium, which was sponsored by the Institute for Translational Medicine, as well as the University of Chicago Medicine, Kovler Diabetes Center, and Celiac Disease Center, highlighted the many opportunities nurses have to conduct their own research.

Julian Solway, director of the ITM, served as a member of a panel discussion on research and multidisciplinary collaboration. He emphasized that a nurse can serve many complex roles across the research spectrum, and that collaboration among physicians, nurses, laboratory staff, and other health professionals is critical in advancing research as a whole.

The overall response to the symposium was one of enlightenment and enthusiasm among the more than 80 nurses in attendance.

“I’ve sometimes felt that there wasn’t anyone dedicated to helping us advance,” said Sandra Leon, RN, BSN. “It’s great to know who those people are, and to make those contacts here.”

“Without the help of the ITM, this conference would not have happened,” said Suling Li, RN, PhD, manager for nursing research at the Center for Nursing Professional Practice and Research. “The conference definitely exceeded my expectations — I loved the energy in the room and all the wonderful exchanges that occurred.”

The ITM strives to speed the progress of laboratory research into healthcare practice and improved community health. We connect researchers and community organizations with funding, education, and resources to find effective ways to prevent and treat disease in real-world settings.

Above: ITM Director Julian Solway (left) and Anne Pohlman, Pulmonary and Critical Care nurse, react to a comment during the multidisciplinary collaboration panel at the 2012 Nursing Research and Evidence-Based Practice Symposium.

Matthew Tirrell, PhD, Pritzker Director and Professor at the Institute for Molecular Engineering, and Senior Scientist at Argonne National Laboratory, presented attendees of last night’s Advanced Tools in Translational Science seminar.

As Tirrell indicated during his presentation, the technology shows promise in terms of targeted drug delivery or therapeutic methods, and has potential for application in translational science studies.

For more information about Tirrell’s work, visit the Institute for Molecular Engineering website. seminar with a unique opportunity for collaboration. The seminar, which was the last in the series for the 2011-12 academic year, showcased the possibilities for translating nanotechnology as exemplified by protein analogous micelles.

Watch for news regarding the start of the 2012-13 Advanced Tools in Translational Science Seminar Series, which will begin this fall.

“Quality Champions: Building improvement skills of front line staff”

Ken Anderson, DO, Chief Medical Quality Officer, NorthShore University HealthSystem
Deborah Kull, Vice President for Operational Excellence, University of Chicago Medicine

The presenters will discuss programs in place to create a group of front line quality improvement champions. Ken Anderson will discuss work on a Quality Fellowship program to recruit, train, and unleash quality champions at NorthShore. Deborah Kull will discuss the implementation of Lean at UCM. Both presenters will discuss how front line champions are addressing pitfalls and cultural challenges, and how organization leaders can help them celebrate the triumphs of improving their health system.

Friday, April 27, 2012
4–6 p.m.
Evanston Hospital, Room G966
Doctors’ Dining Room (ground floor)

A wine and cheese reception will follow the presentation and discussion. Parking in the hospital garage will be validated. Please RSVP to Jackie Doernberger at jdoernberger@northshore.org.

Monday, April 30, 2012
5–6 p.m.
Kodak Room, P118 (please note location change)
Light refreshments will be provided.

Enter through the Billings Hospital Goldblatt Pavilion; take the right-hand corridor. Turn left at the M corridor (following signs for Elevator P West). Turn right onto the P corridor. The Kodak Room will be clearly marked on your left, just past the elevator.

The Advanced Tools in Translational Science Series focuses on presenting novel or emerging technologies to enable T1 translational researchers to advance their studies. These new technologies have tremendous potential to advance our understanding of human health and disease and to inform the development of personalized approaches to disease prevention, diagnosis, and treatment. Coordinated by the University of Chicago Institute for Translational Medicine, these seminars provide valuable and useful tools and information to faculty members, students, and trainees at all levels who are interested in cutting-edge research approaches at the first level of translation (from laboratory findings to clinical practice). University of Chicago faculty experts and guest speakers will describe molecular, cellular, genetic, and biophysical methodologies as well as where to find resources to utilize these up-and-coming techniques (including their advantages and pitfalls).

Please contact Shanna Williams (swilliams6@bsd.uchicago.edu) with any questions.

It’s important to take the time to build a number of relationships with the residents of the community you’re proposing to study. Whether it’s a pilot study proposal, or a larger grant-funded study, the resources and cooperation created by relationship development are keys to a successful outcome.

Here are three places to go when you’re trying to build trust and relationships within a community:

Go to school

If you’re planning a pilot study that involves pediatric patients, try attending school board meetings. Talk to parents. Community issues are often discussed in addition to school issues, and people involved in their children’s school are often involved elsewhere in the community, creating more doorways of opportunity.

Go to church

Churches play a big part in Chicago’s South Side communities, and often have health ministries or health advisory boards that can help you understand what the surrounding community’s biggest health issues and concerns are.

Go to health fairs

Community health fairs are a great place to find out what’s of most interest or importance to the community members with whom you want to do collaborative research.

And don’t forget…

The ITM has an entire Community Cluster, full of resources and expertise that investigators can utilize while planning or carrying out community-based research. If you’d like more information, contact Chartay Robinson at crobinson1@medicine.bsd.uchicago.edu

Tips courtesy of Connie Robinson, RN, MBA, MSN; Research Subject Advocate

One of the best things about education is that you can always pick up right where you left off. But that option can also make it hard to finish what you started.

After three years at Northern Illinois University in DeKalb, Ill., Candice Sherman (pictured at right) had exhausted her financial aid and was forced to return home to Chicago. She immediately went to work, but it wasn’t long before she understood that she needed to finish her degree.

“I didn’t want to get complacent,” Sherman said. “It’s so easy to just get a job, to make a living. But you have to get your degree if you really want to get anywhere.”

With tuition costs constantly rising, Sherman figured that community college was the way to go. After that, she made a plan: she was going to knock out her prerequisites at Kennedy King College (KKC), and then apply for nursing school at a college where she could also get a bachelor’s degree in business.

“So many people want to be in the medical field,” Sherman observed. “I knew I had to do something to set myself apart from the rest.”

Mario De La Haye, a professor in the Biological Sciences Department at KKC, had become a mentor to Sherman and had counseled her on future career moves. He informed her of an opportunity available through a partnership between the University of Chicago’s Institute for Translational Medicine (ITM) and KKC, called the Chicago Partnership for Research and Training in Health Disparities (CPRTHD).

Funded by an American Recovery and Reinvestment Act (ARRA) supplement to the ITM’s Clinical and Translational Science Award (CTSA), the pipeline program helps educate future health care professionals about the health disparities found on the South Side of Chicago, encourages them to finish their studies, and also provides them with a mentorship experience. By partnering with Kennedy King and Chicago State University, the program is able to reach students who may have witnessed these disparities first-hand and have a personal interest in improving health care in underserved populations.

Sherman applied to the program and was accepted as a part-time intern in June 2010. In January 2011, she was hired on as a full-time project assistant in the Section of Pediatric Infectious Disease, led by Kenneth Alexander, MD, PhD. While there, she’s been able to work on the In-School Immunization Program, which has administered vaccinations to more than 60 students in eight Chicago Public Schools to date.

“As an intern, and now as a project assistant, I do a lot of administrative tasks,” Sherman explained. “But I also get to work with children, teachers, and parents, educating them about who we are, what we’re doing and why. I help them understand why immunization is important.”

Sherman has also participated in focus groups, where she and other investigators have learned valuable information about why parents may not want to have their children immunized. This information helps them in future public education efforts, enabling them to better inform audiences and dispel inaccurate or negative views on immunization.

“This opportunity helped me understand what it’s like to actually be a nurse,” Sherman reflected. “It made me think: Do I want to work in a hospital setting? Am I comfortable dealing with parents? Do I want to work with the community?”

For Sherman, that last question became one of utmost importance as she began to see exactly how large the gulf was between health care on the South Side of Chicago and care in schools farther north.

“Some people don’t know anything outside of what they see,” Sherman said. “Kids who live in Washington Park don’t get the same care as kids in Roscoe Village.”

“There’s also a lot of ignorance about the fact that people [on the South Side] want to be there for their kids,” she continued. “But when they have to work two or three jobs to make ends meet, that becomes more and more difficult.”

The key to treating health care disparities, Sherman believes, is not just funding. It’s also finding those people who care more about doing good than how much they’re getting paid.

“It takes a different kind of person,” Sherman said. “It can be hard.”

As far as the program itself, and the opportunities it’s provided, Sherman has no doubt that the CPRTHD has — and will continue to have — an effect on her future success as a nurse.

“I’ve always wanted to work in pediatrics,” Sherman said. “Being surrounded by pediatric nurse practitioners every day is a blessing. I’m growing by being around them. I’m learning. And I have to keep advancing so that someday, I can open doors for others. I was given an opportunity, and I’d like to be able to do the same thing for someone else.”

Connie Robinson has always been involved in research. Even as a clinical nurse associate in pediatric nephrology, she was assisting the department with study coordination. But her role as a research subject advocate (RSA) and her specialization in ethics are things that came to her by pure chance.

“Dr. Lainie Ross was leading a focus group at my church,” Robinson recalled. “She was surveying African American women’s attitudes toward genetic screening, and I thought it sounded interesting. After the meeting, she invited me to an ethics case conference.”

The simple decision to attend the focus group, and then the ethics case conference, led to a bioethics fellowship with the MacLean Center for Clinical Medical Ethics. These days, Robinson splits her time between pediatric nephrology and research subject advocacy.

“[In my role as a research subject advocate] I talk to parents and make sure they fully understand the study they are enrolling their child in, and that they understand the difference between research and clinical care,” Robinson explained. “I also make certain that the child knows their participation is completely voluntary, and that they can say no at any point — that no one is going to be mad at them.”

Robinson also has the opportunity to work with UChicago researchers. She reviews protocol submissions made by ITM investigators, before those submissions reach the Internal Scientific Review Panel (ISAP).

“Any time a protocol involves pediatric subjects or the community, it comes to me for data safety and monitoring review,” Robinson said. “I address physiological safety issues as well as issues concerning privacy, confidentiality, and potential for stigmatization. And I also emphasize to the investigator their responsibility to have a method of informing potential research participants if a medical condition is discovered during eligibility screening for the study.”

All of this gives the investigator time to tweak their protocols before ISAP review, thereby increasing their chances of successful funding applications for pilot funding and other awards.

“It’s so fulfilling, informing people — especially out in the community — about research,” Robinson said of her role as research subject advocate. Of course, there’s difficulty in the role, too. “Sometimes you see excellent ideas for clinical studies, but you’re not able to see them all happen.”

Her suggestions for writing a successful human subject section of an application:

• Make sure you fully address privacy and confidentiality issues.
• If it is a community-based study, make sure you’ve established trust in the community.

“This isn’t like a test at school where you’re cheating if you get help, or have the answers ahead of time,” Robinson said. “We want you to succeed. Everyday advances are the results of research success.”

Juliane Bubeck Wardenburg (left) and a member of her research laboratory, Naoko Inoshima, PhD

It’s a common catch-22 in the clinical research world that you can’t get funding without preliminary data, but you also can’t get preliminary data without funding. That’s the situation Juliane Bubeck Wardenburg, MD, PhD, Assistant Professor of Pediatrics and Microbiology, found herself in a few years ago when she embarked on a new series of studies of Staphylococcus aureus in 2008.

Bubeck Wardenburg had a long-standing interest in Staphylococcus aureus (S. aureus), and over the years had learned that in cases of pneumonia, the bacteria generated a toxin called a-toxin that targeted lung cells in a very
specific way.

“You can think of the toxin almost like a missile,” Bubeck Wardenburg explained. “It gets sent out from the bacteria, lands on the lung cell, then punctures the membrane of the cell, effectively destroying the cell.”

Bubeck Wardenburg wanted to find out how the toxin was able to so accurately target and injure the lung cells. She had a hunch that it would be a vital part of finding new methods to treat pneumonia, as well as other S. aureus infections. But she knew that in order to develop these ideas, she needed a pilot grant.

“Pilot funding is intended to catapult an idea that’s new, and then hopefully give it some legs so it can get farther in the clinical research process,” Bubeck Wardenburg said.

Bubeck Wardenburg applied for and was awarded a preclinical pilot study grant from University of Chicago’s Institute for Translational Medicine. The ITM provides not only preclinical, but also human subjects, community, and collaborative pilot study funding to clinical researchers at the University of Chicago. The $20,000 grant Bubeck Wardenburg received enabled her to find out just how the a-toxin was able to destroy healthy human lung cells. The key — or rather, the “target” — was a cell surface enzyme known as ADAM10.

“ADAM10 acts as a receptor for the toxin,” said Bubeck Wardenburg. “So if you eliminate ADAM10, the toxin doesn’t act anymore. It can’t locate and bind to the host cells.”

The initial studies from the Bubeck Wardenburg laboratory demonstrated this to be true in lung cells maintained in tissue culture. The discovery was precisely the sort of thing Bubeck Wardenburg hoped to find — an observation that led to other questions and more ideas for preclinical studies.

“We wanted to find an animal model system in which we could eliminate ADAM10, just like you can do in tissue culture,” Bubeck Wardenburg said. “The thought was that if an animal doesn’t have the target for the toxin, it should be resistant to staphylococcal disease.”

Bubeck Wardenburg requested another round of pilot funding, and this time was awarded a grant of $40,000. Once funding was secured, she could work full speed on her second study.

“ADAM10 is required for normal growth and development of an animal,” Bubeck Wardenburg said. “So what we had to do was use a conditional knockout approach, picking ADAM10 as our specific genetic target in the lung cells and skin cells (where the toxin causes injury as well). With this approach, ADAM10 is only eliminated in those tissues.”

Bubeck Wardenburg and her team were able to breed mice in two groups — those without ADAM10 in the lung, and those without ADAM10 in the skin — through an elaborate animal breeding strategy in the first seven months of funding. These mice led to some new potential treatment methods.

“The mice without ADAM10 in the lung were resistant to deadly pneumonia infection, and the mice without ADAM10 in the skin were resistant to severe invasive skin disease,” Bubeck Wardenburg said.

Not only that, but Bubeck Wardenburg noted that the bacteria had an interesting effect on the natural function of ADAM10.

“When the toxin binds to ADAM10, it activates a very specific function,” she explained. “ADAM10 acts like a pair of scissors. Its natural function is to cut proteins that hold cells together so that they can separate and make room for new cells, allowing for normal cell turnover and growth.”

But the toxin seems to accelerate this “scissor function,” causing cells to cleave apart when there are no new cells available to replace them, resulting in further injury to tissue in the lungs or skin. Once Bubeck Wardenburg realized that the ADAM10 enzyme’s role in S. aureus infection was two-fold, it became clear that an enzyme inhibitor, which binds to ADAM10 and decreases its activity, may be a novel way of preventing or treating infection.

“Usually when we think of drugs that we’d use to treat infections, those drugs target the bacteria,” Bubeck Wardenburg said. “This approach has become very problematic, because bacteria can rapidly develop resistance to treatment. Our new method targets the host. The host cells will not be able to resist the effects of the drug. They can’t change at the rate bacteria can. So it’s a very unique strategy.”

It is an exciting discovery, especially when considering treatment for at-risk populations. But as with any new clinical treatment method, development is not without its challenges.

“There is actually an entire group of enzymes in the ADAM family, and they’re all structurally similar,” Bubeck Wardenburg explained. “Not only will the new drug need to have a high potency, it will need to have high specificity as well.”

“A second, very big challenge is that you’re shutting down a process that the host’s body needs to perform,” she continued. “So it begs the question of safety in that, how long can you shut down ADAM10 before you start to see a negative effect on the host?”

The results from Bubeck Wardenburg’s two pilot studies have continued to advance along the translational research spectrum. A vaccine strategy developed as a result of the first pilot study is close to clinical trial phase with a pharmaceutical sponsor company. Bubeck Wardenburg is also in talks with the NIH about drug development for the specific enzyme inhibitor that would shut down ADAM10 activity. Her study on S. aureus bacteria and ADAM10 in lung cells was featured in Nature Medicine in October 2011. A separate study on the bacteria’s interaction with skin cells will be published in the Journal of Investigative Dermatology in early 2012.

Bubeck Wardenburg was insistent that were it not for thepilot funding from the ITM, none of this would have been possible.

“The pilot funding enabled us to do something that was genetically complicated and allowed a new approach to the disease problem,” Bubeck Wardenburg said. “This strategy, used in concert with a traditional course of antibiotics, could make a bigger impact. It could change the duration and severity of infection; it could reduce the number of hospitalizations and surgeries. This could completely change how we treat infections.”

The new ITM Pilot Awards Program Request for Applications (RFA) has been posted online. ITM Pilot Awards provide funding for promising translational and clinical research projects. Click here to view the new RFA.

The next application deadline is April 15, 2012. All applications submitted for the upcoming deadline or later must use the new RFA. Applications that are completed using a previous version will be returned to the investigator.

For more informaiton about the ITM Pilot Awards Program, visit the Pilot Awards page.

Please join us for the next lecture in the monthly ITM Advanced Tools in Translational Science Seminar Series:

Next generation sequencing and its applications: Short and long term adaptations in primates through changes in gene regulation

Speaker: Yoav Gilad, PhD, Associate Professor, Department of Human Genetics

Monday, March 26, 2012
5:00–6:00 p.m.
Medical Center Conference Room H300 (conference room in the W300 suite)
Light refreshments will be served.

The Advanced Tools in Translational Science Series focuses on presenting novel or emerging technologies to enable T1 translational researchers to advance their studies. These new technologies have tremendous potential to advance our understanding of human health and disease and to inform the development of personalized approaches to disease prevention, diagnosis, and treatment. Coordinated by the University of Chicago Institute for Translational Medicine, these seminars provide valuable and useful tools and information to faculty members, students, and trainees at all levels who are interested in cutting-edge research approaches at the first level of translation (from laboratory findings to clinical practice). University of Chicago faculty experts and guest speakers will describe molecular, cellular, genetic, and biophysical methodologies as well as where to find resources to utilize these up-and-coming techniques (including their advantages and pitfalls).