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discover UNMC SPRING 2015 UNMC’s 2014 Scientist Laureate seeks new drug delivery systems on the nano scale UNMC WILL LEAD IN RESEARCH U have launched a new mission that improve how we work together to solve states we “will lead the world in complex problems, which may, more and transforming lives to create a healthy future more, require teams that include new or for all individuals and communities through special expertise, such as mathematical premier educational programs, innovative modeling, engineering and material science. NMC and Nebraska Medicine research and extraordinary patient care.” As UNMC makes its impact on Our research community continues to Key members of those teams will include health care providers and public innovative research, this issue highlights health practitioners who can bridge the the increasing range of research initiatives research gap and work with those who UNMC has with partners near and far. know more about patient care or public These articles span bench research, from DNA mutations to biomedical health improvement. In the end, the goal is to make a difference in people’s lives. informatics that link different kinds of data to the best therapeutic strategy for a person’s cancer. We have translational investigators, like our Scientist Laureate Tatiana Bronich, Jennifer Larsen, M.D. Ph.D., who seek to use nanomedicine UNMC Vice Chancellor for Research approaches to improve therapies so they are more effective, easier to take or better target the disease, wherever it might be. Our patient-centered research evaluates new ways to address disease on a patientby-patient basis. Research teams work to improve care of those with diseased blood vessels located outside the heart, to advance treatment in communities by harnessing the best ideas of groups of primary care practitioners with a research network, and make a difference in global settings, such as Africa. UNMC Discover is published twice a year by the Vice Chancellor for Research and the Department of Public Relations at the University of Nebraska Medical Center. The magazine is supported by the UNMC chancellor. Issues of the magazine can be found at www.unmc.edu/discover. Permission is granted to reprint any written materials herein, provided proper credit is given. Direct all requests to [email protected]. Subscriptions to UNMC Discover are free. For a printed or email subscription, go to unmc.edu/discover. We are Nebraska Medicine and UNMC. Our mission is to lead the world in transforming lives to create a healthy future for all individuals and communities through premier educational programs, innovative research and extraordinary patient care. UNMC is accredited by The Higher Learning Commission of the North Central Association of Colleges and Schools (HLC-NCA) and enjoys full accreditation of all its professional academic programs. UNMC does not discriminate in its academic, employment or admissions programs and abides by all federal regulations pertaining to same. Because our mailing list comes from multiple databases, some readers may receive duplicate copies. Please share extra copies with someone else, or send us the address panels from all the copies you receive and we will be glad to eliminate the duplication. Send to: UNMC Public Relations, 985230 Nebraska Medical Center, Omaha, NE 68198-5230, or call 402.559.4353. Director of Public Relations: Bill O’Neill Senior Associate Director: Karen Burbach Publications Editor: Elizabeth Kumru Design: DAAKE Photography: Peggy Cain David Hussey Brandon McKenna Public Relations staff Research Resource Board: Jennifer Larsen, M.D. • Ken Bayles, Ph.D. Chris Kratochvil, M.D. • Laura Bilek, Ph.D. Bradley Britigan, M.D. • Marlene Cohen, Ph.D. Kenneth Cowan, M.D., Ph.D. • Dele Davies, M.D. Michael Dixon, Ph.D. • Anna Dunaevsky, Ph.D. Courtney Fletcher, Pharm.D. • Howard Fox, M.D., Ph.D. Janet Guthmiller, D.D.S., Ph.D. • Ali S. Khan, M.D., M.P.H. Mike Leibowitz, M.D., Ph.D. • Ram Mahato, Ph.D. Kyle Meyer, Ph.D. • Amarnath Natarajan, Ph.D. Jeffrey Payne, D.D.S. • Juliann Sebastian, Ph.D. Mohammad Siahpush, Ph.D. • Paula Turpen, Ph.D. Jonathan Vennerstrom, Ph.D. discover UNMC SPRING 2015 CONTENTS: ON THE COVER: Tatiana Bronich, Ph.D., is named the 2014 Scientist Laureate, the highest honor given to a UNMC researcher. FE ATURES: 6 10 A nanopioneer seeks novel drug delivery systems UNMC’s ninth Scientist Laureate is hooked on innovation. WANTED: Stents that work well for peripheral artery disease 23 A $3.5 million grant will help researchers understand why stents don’t work well for treating peripheral artery disease. 12 Designer peptides to fight superbugs Engineered peptides may soon be the therapy of choice against nasty web bacterial extra and viral infections and even cancer. web extra 14 unmc.edu/connect 20 Computers help physicians determine best treatment plan The genesis of cancer mutations New prototypes designed for interventional radiology Overexposure to radiation leads one radiologist to invent protective devices. web extra IBM Watson searches millions of data points to improve care for cancer patients. 16 18 Study to help HIV-infected women live normal lives Some antiretroviral therapies used in sub-Saharan Africa are found to not work well with contraceptives. 22 DEPARTMENTS: 2 Vice Chancellor Message 4 UNMC News 8 Distinguished Scientists Honored web 23 Under the Microscope extra web extra What? No magic way to lose weight? Family practice physicians get together to help motivate patients to lose weight. unmc.edu/connect web extra web extra unmc.edu/discover web extra web extra web extra The vicious cycle of DNA mutation is revealed. web extra web extra unmc.edu/connect web extra FOLLOW US: facebook.com/unmcedu twitter.com/unmc youtube.com/unmcedu pinterest.com/unmc unmc.edu/connect news UNMC Center for Substance Abuse Research approved “Substance abuse leading to addiction is often accompanied with mental illness and currently being done by the Buch laboratory. continues to be one of the most devastating This center is a natural next step in its problems facing communities throughout evolution,” said Howard Gendelman, M.D., the world,” said Shilpa Buch, Ph.D., center chairman of pharmacology and experimental director and professor of pharmacology and neuroscience. “The impact to our university experimental neuroscience in the College and its mission is boundless.” of Medicine. The mission of the center is to bring the “The interdisciplinary capabilities and approaches that will come together in power of science and research to bear on the center will make UNMC a leader in drug abuse and addiction, thereby improving combatting the plague of substance abuse the quality of life of the affected individuals, that brings pain and suffering to so many,” while reducing the health care costs in said Bradley Britigan, M.D., dean of the the state of Nebraska through innovative UNMC College of Medicine. collaborative basic and clinical research, The center builds on existing and planned premier education programs, and outreach to collaborations with other institutions and those suffering from addiction. universities, including the VA Medical Center, The Nebraska Center for Substance University of Nebraska-Lincoln, Creighton Abuse Research, approved by the University University, Kansas University Medical Center, of Nebraska Board of Regents in April, brings University of Minnesota, Emory University, together scientists from multiple Colleges as well as Nanjing University in China and he new Nebraska Center for Substance at UNMC as well as from the University of two institutes in India -- the Brain Research Abuse Research at UNMC will promote Nebraska at Omaha and the University of Institute, Manesar and Jawaharlal Nehru Nebraska-Lincoln. Institute of Advanced Study. Shilpa Buch, Ph.D. T an extension of all the outstanding work and facilitate research in understanding consequences and prevention of drug abuse and neurodegenerative diseases. “The mechanisms, the treatment and prevention of substance abuse is Postdocs teach, mentor as part of new partnership A new partnership as formed between UNMC and Metropolitan Community College. UNMC’s post doctoral education office The partnership grew out of a seminar what they’re getting into,” Dr. Ahmad said. series on professional opportunities for “At the same time, they can put it on their postdocs, said Iqbal Ahmad, Ph.D., associate resume, and that experience in teaching will dean and director of postdoctoral education. make them much more marketable.” MCC was a good fit, he said, because and MCC’s department of mathematics One seminar on careers away from the and natural science will work together to bench was about teaching, and among the it has many classes on the weekend and provide teaching opportunities for UNMC speakers were educators from MCC. in the evenings, so postdocs would find it post-docs and mentorship opportunities for MCC students. “I thought, ‘Wouldn’t it be nice if our postdocs can get an opportunity to teach, so they have the experience and they know 4 SPRING 2015 easier to fit into their bench work schedules. Study to compare gout treatments A gout epidemic is sweeping the U.S. Four percent of the Study shows vitamin D protects bones in mice exposed to agricultural dust; may have implications for ag workers U.S. population has gout, Though they did find a slight effect and the number is going on reducing inflammation in the up rapidly. It has become lungs of mice, they found a the most common form statistically significant effect on of inflammatory arthritis in James O’Dell, M.D. protecting the bones. adults. It also is associated “We found if we gave vitamin D, with significant morbidity the mice didn’t get bone loss,” said and mortality in older men and magnified in patients with chronic kidney disease. Jill Poole, M.D., associate professor Jill Poole, M.D. James O’Dell, M.D., Bruce professor and chief of the UNMC Division of Rheumatology and Immunology, is the principal investigator on a four-year, $23 million VA Cooperative Study titled “Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat.” The study will include 950 patients from contracted sites around the country, including UNMC, various Veterans Administration Medical Center sites and various Rheumatoid Arthritis Investigational Network sites. Because gout is common in the demographic of the VA patient population, this study could lead to significantly improved patient outcomes. Documentation shows gout is the most mismanaged chronic disease there is, Dr. O’Dell said. Ninety percent of patients with gout have problems with chronic gout. This number should be less than 10 percent if properly managed. “The prevalence of gout in patients with renal failure is upwards of 30 percent,” Dr. O’Dell said. “Our study will be the first time that a substantial number of patients with kidney disease, who have gout, will be studied.” According to the proposal, two drugs have been endorsed as first-line treatment for gout, allopurinol and febuxostat. Both drugs are effective and generally well tolerated, but febuxostat costs considerably more. However, according to a previous survey of 179 VA practitioners, febuxostat appears to be the drug of choice. The reasoning seems to be the perception that febuxostat provided superior efficacy and tolerability. A in the UNMC Department of Internal Medicine and principal investigator of small animal study led by the study published in the scientific UNMC, the first model linking journal, Immunology Research. inhalant agriculture organic dusts to “There was some benefit of causing systemic bone deterioration, reducing inflammation in their found evidence that may contribute lungs, but it completely protected to the growing knowledge of benefits their bones. This is important of vitamin D. because emerging data in humans Researchers found that mice suggests that generalized chronic exposed to hog barn dust over three lung inflammation is a risk factor for weeks had a statistically significant osteoporosis and fractures.” bone loss – 5 percent to 20 percent. Dr. Poole encourages those who But they had no bone loss if they work in agricultural dust environments received a high dose supplementation to wear protective respiratory of vitamin D. equipment and take vitamin D. It’s well known that agriculture “As a bone protective strategy, workers have high rates of airway people particularly with underlying inflammatory diseases including respiratory disorders and symptoms, asthma-like disorders and chronic might want to consider taking over- bronchitis and high rates of the-counter supplemental vitamin musculoskeletal diseases, including D3 – 2,000 to 4,000 IUs daily as long bone fractures. as they don’t have any other health One of the study goals was to problems,” she said. “If they do have see if high dose supplementation of health problems, they should first vitamin D would help protect against talk to their doctor before taking the adverse outcomes due to inhaling the vitamin.” dusts in the agricultural environment. This study will compare the two therapies for 5 lowering uric acid levels to see which is the most clinically and economically effective, Dr. O’Dell said. UNMC discover Tatiana Bronich, Ph.D., professor of pharmaceutical sciences in the College of Pharmacy, co-director of the Center for Drug Delivery and Nanomedicine, and recently named UNMC’s ninth Scientist Laureate, credits those who came before her. Foremost, her mother. “Professor Galina Sirtsova,” Dr. Bronich said, “a wonderful person, scientist and educator, who has been one of the leaders in the development of chemical sciences and chemical education in Moldova.” Dr. Sirtsova is noted in a book celebrating that nation’s outstanding women, Dr. Bronich said. By age 11, Dr. Bronich was helping her mother grade exams. She received a first-hand view of a scientist’s life. Her mother, a department chair, was a tremendous role model. It could be exciting. It could be frustrating. “She was very, very devoted,” Dr. Bronich said. In watching her mother, Dr. Bronich knew what she wanted to do. “My memories of her have always carried me through many moments of doubt and hopeless situations,” she said. A nanopioneer seeks novel drug delivery systems 6 by Kalani Simpson SPRING 2015 Dr. Bronich became fascinated by chemistry. Her mentor in Russia was the father of 2009 UNMC Scientist Laureate Sasha Kabanov, Ph.D. Dr. Kabanov, now at the University of North “Sometimes the view of the problem might be different,” Carolina Eshelman School of Pharmacy, eventually helped recruit Dr. Bronich said. “And that’s where the breakthrough ideas and Dr. Bronich to UNMC. decisions can come.” “He helped me take the first steps, not only in biomedical research, but also here, in America,” Dr. Bronich said. In Russia, Dr. Bronich had been an expert in synthetic polymers. But at UNMC, she stepped into a new world, in trying to help find an application for them in biology and medicine. “This was of course very new, very exciting,” Dr. Bronich said. But it was also very tough to find a niche, to make that bridge. “When you start to do something new, it’s not very easy. There is no one who did it before that you can follow. You’ve got to explore the field, learn a lot of new stuff. And plus, you’ve just come to a new country.” It was 20 years ago, in 1995, that Dr. Bronich came to the United States. But in the 20 years since, she’s learned a lot of new stuff, found a home in this new country. She holds joint citizenship – she will always be Russian. But now she is American, too. And she’s found her niche. Loves her job. She is part of a group working to design polymers to interact with therapeutic-friendly molecules as a drug-delivery vehicle, even targeting specific sites through nanomedicine. To explain further, there are drugs that would work … but don’t have good properties for delivery. “That’s why they are out of the scope,” Dr. Bronich said. “We try to rescue them, make them safer, and eventually move these drugs into clinical application.” Much of this work is applicable to cancer. They work to not only better target the bad stuff, but leave good tissue unharmed. “We try to make such systems ‘smart’ in a way that they can switch on and off certain properties, depending on the physiological It’s that type of thinking that drives Dr. Bronich’s most wideranging project. She is program director and principal investigator of a Center of Biomedical Research Excellence (CoBRE) grant in the Nebraska Center for Nanomedicine. It’s a cross-academic center, featuring six projects and funded by $11.2 million over six years. “Whatever we achieve,” she said, “whatever our achievements are, they are not because of one individual. Usually the achievements are done by a group of people, through very close collaboration.” Dr. Bronich said she was surprised to have been named Scientist Laureate, and lauded her lab’s graduate students, postdocs and technicians for their hard work and dedication. She also thanked her dean, Courtney Fletcher, Pharm.D., and department chair, Ram Mahato, Ph.D. And her emeritus dean and chair, Clarence Ueda, Pharm.D.,Ph.D. and Dennis Robinson, Ph.D. Pharmaceutical science staff Chris Allmon and Keith Sutton were cited too. The atmosphere at UNMC, she said, is a collective thing. It comes from everyone. “The collaborative atmosphere here is so great,” she said. “The people are very friendly and very open. They always share their time, their efforts with you, if you need help, if you need their advice.” Now, as a senior scientist, she is doing the same. Twenty years ago there had been no trail to follow in nanomedicine. And Dr. Bronich said, “We’re not there yet. But that’s what science is about. “It’s a long series of the small steps, which every day, every hour, we are making to reach the goal.” surrounding, to maximize the clinical benefits of the treatment.” It’s the kind of thing that happens at a place like UNMC, where people from different disciplines come together to solve problems. Someone with a different area of expertise might see something you hadn’t known to look for. 7 UNMC discover DISTINGUISHED SCIENTISTS HONORED by Elizabeth Kumru E ach year, when UNMC’s emerging and top researchers are recognized, it is clear that the depth and breadth of their work continues to expand. UNMC researchers discover new cells and genes. They investigate how new compounds and genes work inside cells and in animals that have been specially developed to model human diseases. They work to understand if the processes and markers found in those cells or animals are relevant to people. Then they consider whether medications or other interventions that block or stimulate those processes can prevent or change the course of disease. Scientists are not limited to bench research. They also look at large groups of population data to find new patterns or trends and create new interventions to change the health of communities. Increasingly, science requires interprofessional teams. Information that is found in one setting can often prove to be more important to a completely different system or disease. Sometimes new discoveries happen rapidly and sometimes it takes years to achieve a goal. The 2014 roster of Distinguished Scientists, New Investigators, Research Leadership and Community Service to Research Award recipients represents the largest number to be recognized in the nine years of the award’s history. They represent the UNMC Colleges of Dentistry, Medicine, Nursing, Pharmacy, Public Health, the Munroe-Meyer Institute and the Eppley Institute for Research in Cancer and Allied Diseases. Ten Distinguished Scientists were honored for their outstanding research programs, published research results in journals of the highest quality 8 and the ability to attract and retain extramural funding. The Scientist Laureate must meet all the criteria for Distinguished Scientist and conduct research at UNMC for a minimum of five years prior to the award year. The 2014 recipient is Tatiana Bronich, Ph.D., professor of pharmaceutical sciences in the College of Pharmacy. She was first recognized in 2007 as a New Investigator and then in 2011 as a Distinguished Scientist. Nine New Investigator awards went to outstanding UNMC scientists who, in the past one to three years, secured their first funding from federal sources. New Investigators also demonstrated scholarly activity in published research and presentations at national conventions. Scientists who are leaders are particularly valuable. This year, five scientists who have proven to be leaders over the years were given the Research Leadership Award. All had been previously recognized as Distinguished Scientists, have maintained a longstanding research funding history and serve as research leaders and mentors on campus. The Community Service to Research Award went to Jane Rips in recognition of her significant contributions to research as a tireless volunteer who has a long history of actively supporting and advocating for cancer research at the Fred & Pamela Buffett Cancer Center. Said Dr. Larsen: “As always, it is the researchers that lead us forward…and it is their work and their achievements we celebrate.” web extra unmc.edu/discover View photos from the Distinguished Scientists Award ceremony. Read profiles of award winners. SPRING 2015 2014 Scientist Laureate Tatiana Bronich, Ph.D.* College of Pharmacy Drug delivery and nanomedicine 2014 Research Leadership Award Winners Joseph Sisson, M.D.* College of Medicine Lung diseases Keith Johnson, Ph.D.* College of Dentistry Cell adhesion metastasis Kay-Uwe Wagner, Ph.D.* Eppley Institute Breast and pancreatic cancer Hamid Band, M.D., Ph.D.* Eppley Institute Molecular brakes in cancer Michael Brattain, Ph.D.* Eppley Institute Colon cancer metastases 2014 Distinguished Scientist Award Winners Philip Smith, M.D. College of Medicine Ebola virus disease Santhi Gorantla, Ph.D. College of Medicine Translational mouse models Jill A. Poole, M.D.* College of Medicine Agricultural-related respiratory disease Kaustubh Datta, Ph.D. College of Medicine Metastatic progression of cancer Chittibabu Guda, Ph.D. College of Medicine Genomics, bioinformatics and personalized medicine Cyrus DeSouza, M.B.B.S. College of Medicine Diabetes complications Yazen Alnouti, Ph.D. College of Pharmacy Drug metabolism and pharmacokinetics David Oupicky, Ph.D. College of Pharmacy Nanomedicine and drug delivery Pankaj Singh, Ph.D.* Eppley Institute Pancreatic cancer metabolism Jing (Jenny) Wang, Ph.D.* Eppley Institute Colon cancer metastasis Paras Mishra, Ph.D. College of Medicine Diabetic heart failure Natalia Osna, M.D., Ph.D. College of Medicine Hepatitis C, alcohol, innate immunity Kishor Bhakat, Ph.D. College of Medicine Lung cancer Erika Boesen, Ph.D. College of Medicine Kidney function and injury MelissaTeoh-Fitzgerald, Ph.D. College of Medicine Breast cancer research Jixin Dong, Ph.D. Eppley Institute Hippo pathway in cancer Max Kurz, Ph.D. Munroe-Meyer Institute Neurorehabilitation Monirul Islam, M.D., Ph.D. LufeiYoung, Ph.D. College of Public Health College of Nursing Outcomes research in Rural health cancer and Infectious diseases New Investigators Community Service to Research * Denotes previous Distinguished Scientist awardee 9 Jane Rips Cancer research advocate UNMC discover WANTED STENTS THAT WORK WELL FOR PERIPHERAL ARTERY DISEASE by Vicky Cerino R esearchers at UNMC have received a five-year, $3.5 million grant funded by the National Institutes of Health to find out why stents don’t work as well for peripheral arterial disease (PAD) as they do for other arteries outside of the legs. It’s a big problem – the U.S. Centers for Disease Control and Prevention estimates about 8 million people in the U.S. have PAD, including 12 percent to 20 percent of individuals older than age 60. Not to mention the problems PAD causes for those who suffer – it reduces or completely cuts off blood flow in the leg arteries which results in pain and numbness of the feet, inability to walk, wounds that won’t heal, and, in worse case scenarios, amputation of the toes, feet or legs. The risk factors include diabetes, smoking, high blood pressure, high cholesterol, obesity and aging. Jason MacTaggart, M.D., a vascular surgeon, and Alexey Kamenskiy, Ph.D., a biomedical engineer, both assistant professors in the UNMC Department of Surgery, are co-principal investigators of the research study. “There are several ways to treat PAD and all of them leave significant room for improvement,” Dr. MacTaggart said. “It’s frustrating for doctors and patients. Everybody is trying to build a better mouse trap, but nobody has. With the support of the surgery department and our team of collaborators, we are taking a rational approach to figuring out why stents don’t work so well in the legs.” In the past decade, there’s been an explosion of PAD treatment with stents – a less invasive procedure than traditional surgical bypass in which the patient is 10 Stents of different designs used in peripheral artery disease are under study at UNMC. SPRING 2015 Part of the research team at work, from left: Paul Deegan, research associate and mechanical engineer, Alexey Kamenskiy, Ph.D., and Jason MacTaggart, M.D. awake and usually leaves the hospital the next day. Vascular surgeons place stents to help relieve the blockage. Stents, small tubular metal devices that doctors put in diseased arteries to keep them open, work well in the heart, but often fail miserably in the leg arteries. Stent failure requires almost half of treated PAD patients to have repeat procedures after only one or two years, Dr. MacTaggart said. One national study estimated the cost of PAD treatment at $21 billion a year, much of which is attributed to repeat procedures. The research team will approach the problem similar to how Boeing designs airplanes or Ford makes cars – with engineering. Using computer models, engineers will work with the medical research team to determine how the artery functions in the leg and then determine how stents work with the artery. “There’s a lot of work being done in the coronary and carotid arteries but significantly less in the peripheral arteries,” Dr. Kamenskiy said. “The reason why there are so few studies is that leg arteries are difficult to study – the lesions are long, the arteries aren’t as easily accessible and it’s difficult to get donor human tissues to study.” Researchers will study donor cadavers and arteries of various ages and stages of disease to gain accurate information to design computer models that will be used to determine which stent is best to use in individual patients. The computer predictions will be verified in PAD patients receiving stents at Nebraska Medicine, UNMC’s primary hospital partner, and the Omaha VA Medical Center. Dr. Kamenskiy said the goal is to improve stents and to personalize PAD interventions. “We analyze how these stents go into the artery, how they interact with the arterial wall as we walk, and how to make this interaction more favorable,” he said. “Right now there’s a lot of art to using stents in PAD. We are trying to do less art and more science.” For more information, contact Karen Taylor at UNMC at 402.559.3935 or Holly DeSpiegelaere at the VA, 402.995.4171. The reconstruction shows how the peripheral artery (in red) contorts when joints bend. Issue underscores importance of organ, tissue donors Jason MacTaggart, M.D., a vascular surgeon, and Alexey Kamenskiy, Ph.D., a biomedical engineer, said they are able to approach the problem in a unique way because of those who’ve donated their bodies to science and organ donors who’ve said yes to tissue donation. “We are grateful to donors and their families and to the Nebraska Organ Recovery System,” Dr. MacTaggart said. “If someone donates their heart or liver, they help one person. If someone donates their arteries to research, they are potentially helping millions of people. “There is no replacement for human tissues in science. If we don’t have human tissues to study, we’re severely hampered in advancing discoveries in medicine and surgery.” 11 UNMC discover DESIGNER PEPTIDES TO FIGHT SUPERBUGS by Elizabeth Kumru 12 SPRING 2015 Guangshun (Gus) Wang, Ph.D. starts with this structural template when he designs potent compounds against superbugs. The magenta-colored area is where positively charged amino acids are located for optimal bacterial recognition. The green area is where oil-like amino acids are situated to catch or grasp and stick to the superbug surface. A new paradigm of peptide intervention is dawning where engineered peptides may soon be the therapy of choice against nasty bacterial and viral infections, as well as cancer and HIV. “This is an exciting time especially since the pipeline for novel therapeutics to treat drug-resistant infections is dry. Database-guided design is a novel way to approach this problem,” Dr. Wang said. Peptides are naturally occurring tiny proteins that present a vast His work began to be noticed in 2004 when he went live with improvement over traditional antibiotic medications in that bacteria are his massive peptide database, which now contains more than 2,500 far less likely to develop resistance to peptide treatment. peptides from a wide variety of sources, ranging from bacteria, Guangshun (Gus) Wang, Ph.D., associate professor, pathology/ microbiology, received a five-year, $1.88 million grant from the National protists, fungi, and plants, to animals including humans. The Antimicrobial Peptide Database facilitates naming, Institute of Allergy and Infectious Diseases (NIAID), National Institutes classification, statistical analysis, search, prediction and design of of Health, to extract the most critical parameters for designing and novel antimicrobials with desired properties. It is the most popular and optimizing potent antimicrobial peptides, basically, templates for a new comprehensive in the world, has received more than two million web generation of antimicrobials. hits and has been cited in more than 700 journal articles and patents. He’s going after the life-threatening “superbugs” that have the With this NIAID grant, Dr. Wang has expanded his laboratory ability to escape the killing power of traditional antibiotics. The ESKAPE capabilities and is designing new compounds for cancers and other pathogens are Enterococcus faecium, Staphylococcus aureus, human diseases. Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and the Enterobacter species. web extra unmc.edu/discover Find out more about the Antimicrobial Peptide Database. Read Dr. Wang’s latest book chapter on the Improved Methods for Classifcation, Prediction and Design of Antimicrobial Peptides. 13 Guangshun (Gus) Wang, Ph.D. UNMC discover COMPUTERS HELP PHYSICIANS DETERMINE BEST TREATMENT PLAN by John Keenan Babu Guda, Ph.D. T he promised era of precision medicine gets a boost from the Fred & Pamela Buffett Cancer Center through its partnership with IBM’s Watson Genomic Analytics program. It takes only 10 minutes for the IBM program to identify relevant mutations and potential drugs that may be considered in a treatment regime – all based on the patient’s genomic profile and the specific mutations. It’s been described as a cognitive system, one that mimics some, but not all capabilities of the human mind. The capabilities it does have include ingesting large volumes of information, identifying the information that’s relevant and then learning from the results of its use. The Fred & Pamela Buffett Cancer Center at UNMC and Nebraska Medicine is one of 14 leading cancer institutes to partner on the project, which is part of IBM’s broader Watson Health initiative to advance patient-centered care and improve health while building on IBM research advancements. We spoke to Babu Guda, Ph.D., associate professor of genetics, cell biology and anatomy, and director of the Bioinformatics Systems Biology Core Facility at UNMC, about the collaboration. 14 SPRING 2015 Why is the Watson Genome Project an exciting partnership? This is the first time there is a product like this, which can mine through large data points and extract the information in an efficient way. Previously, we had been doing this manually. Each database is different, and we had to go through different types of databases. Each database carries a type of information, but there is no connection between them. And we had to make those connections ourselves, whereas this IBM Watson analytics program can do the same thing and get the information out quickly. What does UNMC’s inclusion in this process say about UNMC’s status in the field? It means that we are one of the leaders in the field in terms of applying the knowledge toward personalized medicine. We are really privileged to have access to this. You are collaborating with Ken Cowan, M.D., Ph.D., director of the Fred & Pamela Buffett Cancer Center, and you will be analyzing cancer genomes. Can you tell me a little more about the work you are doing and the potential application of the work? Right now, it’s only a research project. But eventually, if we are As a researcher, how exciting is this opportunity? It’s definitely exciting. To use an example, think about the days when we didn’t have computers, and we had to log all the information manually. And then, if someone needed to review that information, they’d have to go there manually, open the book and go line by line. satisfied and convinced these products really work, we can apply the Now, we have a tremendous edge over people who don’t have same thing for clinical applications. At this point, there is a project access to this program. initiated with Dr. Cowan that is called the Thousand Breast Cancer Genomes Project. All of the patients are registered at UNMC or at UNMC-affiliated hospitals, and then when the cancer patients visit, we take the samples of breast tumor and also the adjacent normal breast tissue or blood samples from the same patient. We extract DNA and then sequence the DNA of the tumor and normal samples separately. During data analysis, the DNA sequence of the normal tissue samples act as the baseline for the tumor DNA because they’re both from the same patient. We can identify the mutations present in the tumor tissue that are not in the normal tissue of the same patient. That is the information that we feed into IBM Watson, which compares it to millions and millions of data points in its own database, and then identifies the most dangerous mutations. The result is a personalized profile report. It also tells you, because this person has this mutation, this is the most useful treatment strategy So what do you see in the future for this? IBM has been spinning off multiple products, and all of them have the same kind of underlying technology. What we are using is Watson Genomics, but there’s also another product called Watson Oncology. IBM’s collaboration with other universities and cancer centers is producing customized products for those universities based on the data supplied that is proprietary to those hospital systems. In the long run, it requires a lot of collaboration between the researchers and the physicians to integrate the clinical data present in the electronic health records (EHR) with the genomic data. Right now, we’re only feeding the mutation data, nothing else. Eventually, it has to be a comprehensive program that links the genotype to phenotype by integrating the phenotype in the EHR data with genomic and pharmacogenomics profiles of patients. Such a program would that physicians can use. create a robust clinical decision support system for physician use. What kind of patients will benefit from this information? using all the pieces of the puzzle. The ultimate goal is to develop efficient precision medicine strategies Some patients are at a higher risk for breast cancer due to specific gene mutations that they inherit from their parents. But most breast cancer patients have “sporadic” disease, which means the mutations need not have a hereditary basis. Once a genetic mutation profile is obtained, this information can be used to make treatment decisions for all types of patients. 15 UNMC discover The genesis of cancer mutations by Elizabeth Kumru E very great publication, like this one, has a strict proofreader who catches mistakes before the story goes out. Still, genes that disrupt the fidelity mechanisms. misatkes are made. (Oops!) How exactly they do this is unclear. Cells in our body work the same way. Each time a cell divides, the DNA is replicated in an exceptionally Eppley Institute, has studied the flawless process with the help of an mechanisms of mutagenesis associated exonucleolytic proofreader that works with DNA polymerase infidelity. She uses with DNA mismatch repair (MMR) a yeast model to create the same DNA machinery to correct the mistakes. polymerase mutations seen in humans and repaired, but bits and pieces of its In collaboration with colleagues from sequences also are perpetually changed, misplaced and swapped – a process published a paper in PNAS that describes that produces mutations. Still, only one a “previously unappreciated pathway” mutation gets through for every one billion triggered by a colon cancer-associated DNA nucleotides. Basically, every time a cell polymerase mutation. body. That’s normal. In contrast, the rate of mutation in cancer SPRING 2015 decipher the mechanism of their action. Umeå University, Sweden, she recently divides, one mutation occurs in the human 16 For the past 25 years, Polina Shcherbakova, Ph.D., associate professor, DNA is repeatedly replicated and Polina Shcherbakova, Ph.D. These hyper-mutated tumors carry mutations in the replicative DNA polymerase Dr. Shcherbakova found that the erroneous DNA synthesis by the polymerase variant, or proofreader, induces checkpoint- cells is much higher. The most hyper-mutated dependent expansion of pools of DNA colorectal and endometrial tumors in humans precursors. This increase, in turn, causes can carry as many as 250,000 mutations. further dramatic reduction in the fidelity of the polymerase, resulting in more errors DNA polymerase genes accumulate, and and continuous activation of the signaling brain or other cancers develop. cascade that keeps the precursor pools Back in 1974, Lawrence Loeb, Mutations in our DNA also occur because of environmental influences, like the sun. Dr. Shcherbakova’s other research M.D., Ph.D., professor of biochemistry, focuses on exposure-induced damage, University of Washington School of for which she has a five-year, $1.1 million into the processes shaping the genomes Medicine, Seattle, introduced the concept grant from the National Institutes of Health of hypermutated human cancers,” Dr. that cancers express a mutator phenotype, that is now in its second round. She also Shcherbakova said. which accounts for the disparity between receives funding from LB506, the Cancer low mutation rates in normal cells and the and Smoking Disease Research Fund 3 percent of colorectal cancer and 8 percent large rate of mutations present in many administered by the Nebraska Department of endometrial cancer, the research has human tumors. of Health and Human Services. expanded. It becomes a vicious circle. “This phenomenon may provide insight While these mutations are only seen in broad significance, Dr. Shcherbakova said. “These numbers represent 10,000 cases a year,” she said. In 2013, a new cancer syndrome also was described in which people who were born with mutations in their DNA polymerase genes begin to develop cancer “The discovery of replicative DNA “Nucleotide pools determine the level polymerase mutations in cancers is a of mutagenesis, so we need to know more beautiful confirmation of these ideas,” about the mechanism in order to design Dr. Shcherbakova said. therapeutics in the future.” The next challenge is to stop the mutations from happening in the first place. “Mutator polymerases are very by their 20s. Somatic DNA polymerase sensitive to nucleotide levels. If they don’t mutations also are seen in other cancers have enough, they don’t make mutations. – gastric, breast and childhood cancers, If they have too much, the cells die due especially brain tumors in children who are to excessive levels of mutagenesis,” she born with defects in DNA mismatch repair. said. “Normal cells are not as sensitive to After a few years, somatic mutations in varying levels of nucleotides.” web extra unmc.edu/discover Read Dr. Shcherbakova’s article in PNAS. Read the commentary on Dr. Shcherbakova’s article in PNAS. 17 UNMC discover NEW PROTOTYPES DESIGNED FOR INTERVENTIONAL RADIOLOGY by Elizabeth Kumru & Tyler Mueller Early tests show that the Lock-Block can reduce radiation exposure by 50 percent. G reg Gordon, M.D., looks like a radiologist on fire with the flaming “I sometimes get home and I can’t walk. I can’t move.” apron he wears at work at the Omaha VA Medical Center. Fortunately, Dr. Gordon, research associate professor, UNMC Dr. Gordon’s garment doesn’t make him hot, but the 30 pounds of lead lining does weigh him down. The lead that shields him from continuous X-ray radiation exposure literally causes pain in his back. As an interventional radiologist, he uses fluoroscopy X-rays, CT, Internal Medicine, is a clever man who has designed two devices that he hopes will cure his pains, and the pains others like him endure. Body stress, strain and injuries are common issues. Up to 75 percent of interventional cardiologists complain about spinal problems, ultrasound, MRI and other minimally invasive image-guided procedures according to a 1997 study conducted by the American College of to diagnose and treat diseases in nearly every organ system. Cardiology. Similar results have been replicated in a recent Society “Basically, I’m a surgeon who doesn’t cut anyone open. I look of Interventional Radiology study from 2015. These injuries are through people using X-ray movies to open blood clots, put in stents. caused by the leaded protection IR physicians wear while standing in We’re vascular plumbers and carpenters,” Dr. Gordon said. awkward positions and angles. He is proud to be part of the exciting field of interventional radiology (IR). For the past 30 years, interventional radiologists have been responsible for much of the medical innovation and development of such minimally invasive procedures as angioplasty and catheterdelivered stents that are commonplace today. Dr. Gordon has had two hip procedures to fix the damage caused by the lead apron and will need another within the year. “My skill sets go down because of the pain and stress,” he said. “It is difficult to maintain the steady hand that I need.” Besides bodily stress, cancers and tumors are another risk from His pains come from the apron, but also from the X-rays he has IR procedures. Working closely with X-ray radiation for extended continuously used to inject dyes and clear arterial blockages in patients periods cumulatively increases the chance of developing health for the past 20 years. It’s not uncommon for him to wear the vest for problems such as cataracts, premature vascular disease, lymphoma, up to 12 hours each day while leaning over multiple patients daily – breast cancer and central nervous system tumors, even when 2,000 a year – with his hands and the left side of his body exposed wearing protective garments. to radiation. 18 SPRING 2015 According to a recent study from Israel, interventionalists (radiology, cardiology and vascular surgery) are three times more likely to die from left-sided versus right-sided brain cancers. Additional cumulative data suggest continuous low dose radiation risk may have an additional risk between 1 and 2.5 percent risk of cancer for the average interventionalist versus physicians who do not use radiation. Three years ago when he was just 46, Dr. Gordon himself was diagnosed with the early formation of cataracts. Current radiation safety standards are based on 1950s data with minimal revisions since, and the Radiation Protection guidelines (ALARA: As Low As Reasonably Achievable) were first adopted in the 1990s. In the interval, European guidelines have become much more stringent with a decrease in whole body exposure by 60 percent and a significant decrease in eye exposure. U.S. guidelines are due to follow soon and more stringent guidelines can mean loss of physician privileges in the interventional suite. There are three rules when dealing with radiation safety – time, distance and shielding. There have been few improvements in the health and safety for IR employees despite the risks, Dr. Gordon said. Attention is growing, however, and monthly position statements discuss the need for improved working environments. So, necessity was the mother of Dr. Gordon’s inventions, which were built around his 2012 start-up company, Radux Devices. UNeMed, the technology transfer office for UNMC, helped him license six patents and launch Radux. A recent $250,000 proof-of-concept grant from the university’s Nebraska Research Initiative has given him the chance to develop and test working prototypes of his flexible sheath and radiation shield. The Lock-Block is a portable shield that allows the physician to work close to the patient, when need requires, while simultaneously decreasing his exposure by 50 to 85 percent. The portable radiation shield, about the size of a steno notebook, blocks X-ray radiation from Lock-Block protects physicians from radiation during procedures that require continuous X-ray imaging and the R2Flex provides distance, support and operator comfort while guiding diagnostic and therapeutic devices into the patient’s blood vessels. the physician’s hands and body. It also helps the IR gain control of the surgical area, and allows the physician to stand in a more ergonomically friendly Greg Gordon, M.D. patented the Lock-Block shield that is designed to better protect physicians from radiation. The shield weighs six ounces and is made of a plastic polyethylene and barium sulfate polymer that blocks and absorbs “scatter” radiation that escapes between the patient and the machine. It is disposable and costs around $60, but Dr. Gordon says his long-term “green” plan is to manufacture shields in different sizes that can be sterilized, with only the pads being disposable. The R2Flex is an attachable extension support sheath that is designed to work alone or with the Lock-Block. The 8-inch long, Teflon coated plastic polymer sheath, reinforced with a stainless steel coil, attaches to a standard vascular access sheath which is secured to the patient with a clip. This allows the IR to work farther away from the radiation field – decreasing the radiation dose by 50 percent. The R2Flex simultaneously allows improvement in guiding diagnostic and therapeutic devices into the patient’s blood vessels with less muscle fatigue demonstrated in proof of concept studies. It is universal in design and can adapt to most sheaths on the market. The two devices, which can be used together or separately, redirect the workflow back to the IR and add stability to the sheath and improve access site management, where wires can sometimes be up to 10 feet long. The final results from ergonomic studies are pending, but less muscle fatigue has been noted, Dr. Gordon said. Before the devices can go on the medical market, they need FDA approval and studies proving their effectiveness. Dr. Gordon said animal studies have found a 50 percent reduction in radiation for one shield and an 85 percent reduction if two shields are used at the same time. Next will be human trials. Building a company from the ground up has been an incredible learning experience. “I was so naïve,” Dr. Gordon said. To counter his lack of knowledge, he is surrounding himself with people who know how to take an invention to the marketplace. He recently signed on former Nebraskan Richard Ganz, now executive-in-residence at the University of Chicago Office of Technology and Intellectual Property, as CEO, and Laura Classen, executive director of Nebraska Angels, as CFO. The prototypes are now made in Utah, but Dr. Gordon said it would be ideal if they were manufactured in Nebraska. 19 position versus standard portable shielding. UNMC discover STUDY TO HELP HIV-INFECTED WOMEN LIVE NORMAL LIVES by Kalani Simpson HIV has gone from being a death sentence to something you treat with pills. Today, those with HIV can, by and large, live normal lives. “I believe that part of HIV becoming a long-term chronic illness is allowing families affected by HIV to have the opportunity to have children and to raise children,” said Kim Scarsi, Pharm.D., associate professor of pharmacy practice. 20 Kim Scarsi, Pharm.D., left, with her team in Uganda. SPRING 2015 In sub-Saharan Africa, that can prove complicated. Resourcelimited settings, Dr. Scarsi said, have much higher levels of maternal and infant mortality and morbidity. But research indicates women in these settings tend to have healthier families when they can plan for them and have some control over their lives and health. Dr. Scarsi is principal investigator of a National Institutes of Healthfunded team working to improve the lives of women in sub-Saharan Africa, where resources tend to be less plentiful than they often are in the U.S., and where HIV infection is a reality for many. But the same antiretroviral therapies that keep HIV at bay – and They found that the hormone concentrations were not reduced can effectively prevent HIV transmission from mother to child – may in one of the anti-HIV drugs. But with the other, the hormone or may not interact well with hormone contraceptives, for those who concentrations were approximately 50 percent lower and three choose to use them. That’s where clinical pharmacology comes in. of the women in that group had an unintended pregnancy while receiving the HIV therapy plus the contraceptive implant. Dr. Scarsi’s collaborators include colleagues from Makarere University and the Infectious Diseases Institute, both in Kampala, Unfortunately, the latter is the preferred anti-HIV medication, Uganda. They studied three groups of HIV-infected women who which is recommended by the World Health Organization as choose to use contraceptive implants – those on two types of the first therapy for all HIV-infected patients. So, the preferred anti-HIV drug does not work as well with antiretroviral treatments, and a third group who were not on hormone contraceptives. antiretroviral meds. (In some countries, not every HIV patient goes immediately to The next step is to try to find a way for the preferred HIV drug antiretroviral meds; instead, levels are monitored until medication is to work with the implant, to help these women have family planning deemed necessary based on national guidelines.) options, in addition to highly effective HIV therapy. Dr. Scarsi recently presented the team’s research findings at HIV Therapy in Glasgow and the 2015 Conference on Retroviruses and Opportunistic Infections in Seattle. But the thing that impresses current Metro Credit Union members the most, is the level of service we provide. Find out for yourself. Visit any Metro Credit Union office and discover how much fun banking can actually be. Maybe the bank you’re looking for, isnt’ a bank at all. Source: Depositaccounts.com Sept., 2014 NCUA 414 S. Saddle Creek Rd. 111th & Maple 72nd & Ames 44th & Center 84th & Q 145th & F 50th & L 402.551.3052 800.301.8549 www.metrofcu.org UNMC discover 21 WHAT? NO MAGIC WAY TO LOSE WEIGHT? Family practice physicians collaborate on weight loss strategies by Lisa Spellman Milo Anderson, M.D. THERE’S NO MAGIC PILL. The project also is focused on measuring Yet, most people still think there are This team of primary care practitioners tricks and shortcuts that will make it simple from four rural towns, Bellevue and Omaha is patient activation and its role in weight to lose all the weight they want and more. learning how to work together, as a primary management, a tool Lani Zimmerman, Milo Anderson, M.D., College of care practice-based research network, to Ph.D., a professor in the College of Nursing, Medicine Class of 1978, surveyed nearly develop projects that will bring providers brought forward as an idea she has used in 1,000 patients earlier this year and found together to discuss their challenges and some of her research. that’s exactly what they think. collaborate on finding solutions together. Dr. Anderson, one of six physicians “These doctors are on the front lines Patient activation is a way of measuring how much an individual feels they can practicing at 23rd Family Med in Fremont, of primary care in Nebraska,” said Jennifer make a difference in their own health and Neb., joined physicians at seven other family Larsen, M.D., vice chancellor for research at health care, said Robert Schwab, M.D., an practice clinics in rural and urban Nebraska, UNMC. “As health care reform continues to assistant professor in the department of as well as faculty from UNMC, to launch impact all of us, we are looking for projects internal medicine. a project aimed at identifying strategies to that will help us identify new ways to attack better address weight concerns in primary complex problems or build new teams our patients, without being condemning, on care clinics. that can enhance individual practices and weight management issues and help them improve the health of Nebraskans.” see the potential positive long-term impact The research project is aimed at understanding factors that lead to One way to do that is to build and test obesity, strategies to reverse it and ways solutions that work and make sense for to get patients motivated to become their Nebraska, she said. own health advocates. It is supported by their involvement will have on their own health,” Dr. Anderson said. In collaboration with a number of UNMC two grants totaling $150,000 from the faculty members, the group decided to Rural Futures Institute and the Nebraska focus on weight management because it is Medical Association with plans to apply a critical issue for their communities and has for national funding. such a broad impact on patient health. Participating sites: “Our next step is to begin to educate Bellevue: Life Care Family Medicine - Brian Finley, M.D., Jacqueline Wells, M.D., Jeff Kasselman, M.D., Cassie Krause, APRN, Connie Daniel, APRN; Nebraska Medicine-Bellevue - Toby Free, M.D. Crete: Crete Area Medical Center - Jason Hesser, M.D., Kate Hesser, M.D., Russell Ebke, M.D., Troy Miller, M.D., Tammy Schroeder, APRN, Kurt Schmeckpepper, PA-C, Kim McMillan, PA-C David City: Butler County Clinic - Gerald Luckey, M.D., Mark Carlson, M.D., Victor Thoendel, M.D., Matthew Summers, M.D., Leah Hays, PA-C Fremont: 23rd Family Med - Milo Anderson, M.D., Monty Sellon, M.D., Paul Glowacki, M.D., Andrew Opp, M.D., Bryce Exstrom, PA-C, Katy Stenger, MPA-C, Lisa Stenvers, PA-C, Cheri Mues, APRN Geneva: Fillmore County Medical Center - Jason Bespalec, M.D., Jeff Hollis, M.D., Aaron Lanik, M.D., Alanna Beckman, M.D., Michelle Dorsey, PA-C, Marirose Fox, PA-C, Russ Coasch, PA-C, Keri Miller, PA-C, Dani Jaeger, PA-C 22 Omaha: Nebraska Medicine-Oak View - Doug Inciarte, M.D.; Nebraska Medicine-Eagle Run Jason Patera, M.D. SPRING 2015 UNDER THE MICROSCOPE by John Keenan YOUNG STUDENTS STOKED ABOUT SCIENCE Speaking to a crowd of approximately 50 middle school students, Greg Karst, Ph.D., never missed a step. “It’s fun to be here,” the College of Allied Health Professions’ assistant dean for academic affairs told the crowd of fifth- through eighth-graders. As part of UNMC’s 2015 Nebraska Science Festival outreach events earlier this year, Dr. Karst – a professor of physical therapy – was one of three UNMC professionals who spoke at area schools. (Kevin McGuire, a laboratory coordinator in the College of Allied Health Professions, and Laurey Math and science teacher Mary Jo Holdcroft Steinke, Ph.D., assistant professor of biochemistry said she appreciated Dr. Karst’s presentation. Her and molecular biology, also visited area schools). class was among those that attended NESciFest Dr. Karst visited St. Matthew’s Catholic School in Bellevue, Neb., to speak about health events at the Durham Museum in April. The Nebraska Science Festival is designed to care careers, including nursing, surgery, family make science accessible, interactive, relevant and medicine, physical therapy and other professions, fun for kids and adults alike. Presented by UNMC, including work in research. NESciFest drew approximately 12,000 people “Much of what people in the health care field do is solve puzzles,” he told his audience. The children wanted answers to two questions to 30 venues in such cities as Omaha, Lincoln, Ashland, Kearney and Wayne this year. Dr. Karst said he enjoyed talking to the – how long would it take to become a health students about science and health fields and care professional, and how much money would seeing their interest. they make. One young man only looked more “We still need good candidates for all our determined when Dr. Karst told him that, from schools,” Dr. Karst said. “I liked their questions eighth grade, he had about 18 more years of school being all over the place.” and training ahead to become a brain surgeon. The students seemed to enjoy Dr. Karst’s presentation. “It was awesome,” said sixth-grader Claire Von Osterheldt, who wants to be a midwife or a pediatric surgeon. “I learned a lot of things.” Sixth-grader Matthew Adkins was interested to Greg Karst, Ph.D., was one of three UNMC professionals who spoke at area schools to promote the Nebraska Science Festival. Stoking the interest of young students is part of the reason NESciFest is so important, he said, and part of the reason that he felt it was important to take part in the outreach event. Next year’s Science Festival is set for April 15 - 23. “We need to get more kids excited about science and provide more opportunities learn how doctors and researchers cured diseases to learn about careers in science and health care,” at UNMC, while fifth-grader Mackenzie Cook was Dr. Karst said. excited to learn about all the different professions. “I want to work in the neonatal intensive care unit (NICU),” said Mackenzie, adding that her aunt is a NICU nurse. web extra unmc.edu/discover Watch the NESciFest video. 23 See a slideshow of this year’s event. UNMC discover discover UNMC University of Nebraska Medical Center 985230 Nebraska Medical Center Omaha, Nebraska 68198-5230 CHANGE SERVICE REQUESTED NON-PROFIT ORG. U.S. POSTAGE PAID OMAHA, NE PERMIT NO.454 Saving the world starts in Nebraska. The world may know UNMC for our expertise dealing with the Ebola virus. But from Falls City to Scottsbluff, the people of Nebraska know us as the champion of a healthy state. From addressing the state’s nursing shortage to training nearly half of Nebraska’s health professionals to – along with our clinical partner, Nebraska Medicine – pumping billions of dollars into the state’s economy each year, UNMC never stops working to make our great state even stronger. UNMC. Breakthroughs for life.® unmc.edu