Institute Awards Second Round of Clinical and Translational Pilot Grants
Posted 7/22/08 - Institute Awards Second Round of Clinical and Translational Pilot Grants
The Institute for Clinical and Translational Research (ICTR) at UW-Madison recently awarded 22 pilots grants (listed below) for translational research projects.
“This second round of awards represents a wide range of compelling research topics, such as the development of a blood test to detect colon cancer, a new method to identify children at risk for obesity, improved treatment strategies for the treatment of kidney disease and community-based approaches to treating tobacco dependence,” says Marc K. Drezner, MD, ICTR director and professor of medicine at UW School of Medicine and Public Health (SMPH). “The research will take place at several locations around the state, including Marshfield, Milwaukee and Madison.”
These awards, totaling approximately $800,000, fall into the categories of clinical and type 1 translational and type 2 translational research.
“Clinical and type 1 translational research involves both clinical trials and translational research that moves from basic laboratory science to clinical trials,” explains Drezner. “Type 2 involves studies out in the real world, often engaging community members, organizations and clinicians as partners in the research process.”
Established in 2007, ICTR was created specifically to enhance the movement of research from the university to doctors’ offices, hospitals and clinics in communities across Wisconsin. Comprised of four UW schools (Medicine and Public Health, Nursing, Pharmacy, Veterinary Medicine), the College of Engineering and Marshfield Clinic, the institute was awarded a $41 million grant in September 2007 from the National Institutes of Health.
“The fundamental goal of ICTR is to link the most basic research to practical improvements in human health,” says Drezner.
In addition to financially supporting new clinical and translational research, ICTR provides infrastructure that links investigators, trains them and provides them many tools and resources.
Type 1 Pilot Projects
Pathogenesis of Childhood Leukemia
Principal investigator (PI): Sinisa Dovat, UW School of Medicine and Public Health (SMPH). Collaborator: Paul Sondel, SMPH.
Leukemia is the most common childhood malignancy. This study proposes to understand the molecular mechanisms that lead to T cell leukemia, specifically by investigating the tumor-suppressing activity of the DNA binding protein, Ikaros. Elucidating this role of Ikaros will potentially reveal additional targets for chemotherapy.
Investigating Genetic Causes of Eye Malformations by High Resolution Oligo Array CGH
PI: Gordana Raca, SMPH. Collaborator: Lisa Schimmenti, University of Minnesota.
In conjunction with the University of Minnesota, this study will examine the role of gene copy abnormalities in the pathogenesis of ocular birth defects. Identifying those regions of the human genome that undergo duplication or deletion in affected individuals will aid in the development of novel clinical diagnostic tools.
fMRI of Anosognosia in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
PI: Michele Ries, SMPH. Collaborators: Sterling Johnson, Mary Elizabeth Meyerand, Howard Rowley, SMPH.
With the prevalence of dementia-related disability expected to increase in the coming years, accurately identifying those at risk early in disease progression is crucial for maintaining brain function. Patients with amnestic mild cognitive impairment (aMCI) display memory impairment without functional difficulties. Nonetheless, those with aMCI who also lack of awareness of memory decline (anosognosia) are at increased risk for a rapid progression to Alzheimer’s disease (AD). This research team will use imaging techniques to investigate whether changes in cortical midline structures of the brain may serve as markers of those at risk to develop AD.
Role of Bone Innervation in Skeletal Adaptation to Loading
PI: Peter Muir, UW School of Veterinary Medicine (SVM). Collaborators: Mary Behan, SVM; Vjeko Miletic, Neil Binkley, SMPH.
This collaborative study between the UW veterinary and medical schools examines the role of sensory nerve function in adaptation of the skeleton to mechanical load. Specifically, the investigators hypothesize estrogen plays a role in the cross-talk between sensory innervation and the skeleton. Elucidating this role will provide further understanding of aging and loss of sex hormones on bone adaptation and potentially identify new targets for the treatment of low bone mass.
Evaluating K-ras and Notch1 Mutations in Precursor T-cell Acute Lymphoblastic Leukemia and Lymphoma Patients
PI: Jing Zhang, SMPH. Collaborators: Ken Young, Sinisa Dovat, SMPH.
Acute lymphoblastic leukemia and lymphoma (PT-ALL) is a common childhood malignancy, of which 10-15% results from abnormal precursor T-cells. By examining the specific nature and frequency of aberrations in key developmental genes from pediatric patients, the researchers will characterize and potentially differentiate T-cell leukemia from T-cell lymphoma. Moreover, using a mouse model system, they will learn more about the primary cell targets of these genetic mutations leading to improved diagnosis and treatment.
Magnetic Resonance Measures of Ganglia Function and Connectivity in Parkinson’s Disease
PI: Catherine Gallagher, SMPH. Collaborators: Sterling Johnson, Aaron Field, Goufan Xu, Barbara Bendin, SMPH.
In Parkinson’s disease (PD), mysterious attrition of brain cells that produce a transmitter molecule, dopamine, results in dysfunction of brain networks that regulate movement. Recent attempts to provide restorative treatment in PD (especially dopamine cell transplants) have failed partially due to lack of physiologic integration of transplanted cells into the brain. Using a variety of imaging techniques, this study will identify new markers of neuronal connectivity and dysfunction.
Real-time MRI in Pediatric Ischemic Brain Injury
PI: Peter Ferrazzano, SMPH. Collaborators: Pelin Cengiz, Mary Elizabeth Meyerand, Howard Rowley, Dandan Sun, SMPH.
In this study, the investigators will use real-time MRI to monitor the physiology of ischemic brain injury in adult and immature brains. Specifically, they will examine the role of cellular ion transport proteins in cytotoxic edema formation after reperfusion of neuronal tissue following ischemia. The unique use of real-time MRI will identify biomarkers of brain injury and the potential therapeutic use of ion transport inhibitors.
Respiratory Impairment and Recovery in Myelin Disorders
PI: Rebecca Johnson, SVM. Collaborators: Ian Duncan, Gordon Mitchell, SVM; John Fleming, SMPH.
Respiratory dysfunction is a common symptom of myelination disorders such as multiple sclerosis (MS). Despite the life-threatening nature of these complications, little is known regarding the mechanism by which demyelination impairs respiration and the impact of non-invasive interventions aimed at subsequently improving respiratory function. Using a well characterized rat model system, this project will provide the foundation for mechanistic studies of respiratory insufficiency and unique translational efforts to improve respiratory function in targeted groups of patients.
Development and Translation of Quantitative Biomarkers of Fatty Liver Disease with MR
PI: Scott Reeder, SMPH. Collaborators: Adnan Said, Rashimi Agni, SMPH; Walter Block, UW School of Engineering (SOE); Venkata Chebrolu, Milwaukee School of Engineering; Jean Brittain, GE Healthcare.
The occurrence of non-alcoholic fatty liver disease (NAFLD), particularly among children, is on the rise. Unfortunately, liver biopsy to detect steatosis, the earliest indicator of NAFLD, is risky and expensive, with high sample variability. A partnership between the School of Medicine and GE Healthcare will continue to develop imaging methodology to diagnosis and quantify steatosis. Successful development of MRI biomarkers will provide clinicians with an opportunity to intervene earlier in the course of this disease.
Bone Microarchitecture in Women with and without Fracture
PI: Richard Kijowski, SMPH. Collaborators: Neil Binkley, Michael Tuite, SMPH.
Bone mineral density is the most commonly used method to measure the risk of osteoporotic fracture. Nonetheless, less than one-half of those who sustain such fractures are classified as at risk. This study will investigate the use of high resolution MRI to identify markers of bone microstructure that are predictive of fracture risk.
A Concise Validation Test of Biomarkers for Colon Cancer
PI: William Dove, SMPH. Collaborators: Richard Halberg, Christina Kendzioriski, Perry Pickhardt, Mark Reichelderfer, SMPH; Steve Yale, Christopher Rall, Marshfield Clinic Research Foundation; Michael Sussman, UW College of Agriculture & Life Sciences (CALS).
This project enlists a truly multidisciplinary team to link basic science with clinical resources at both the UW and Marshfield Clinic to develop plasma biomarkers for colon cancer. The study aims to identify proteins expressed and secreted by early colonic tumors by comparing the array of proteins found in plasma with those found following polypectomy. The validation of such markers can have a major impact on the detection of this human cancer at an early, operable stage.
Development of a Serum Diagnostic for Early Detection of Increased Metabolic Syndrome Risk
PI: Rozalyn Anderson, UW Graduate School. Collaborators: Ricki Colman, Dhanu Shanmuganayagan, UW Graduate School; Alan Attie, CALS.
The dramatic increase in childhood obesity emphasizes the need to identify underlying risk factors associated with disease vulnerability. Development of early diagnostics for increased metabolic syndrome risk will facilitate intervention and preventative treatment, and will also provide insights into the mechanistic basis of the disease. This study will utilize a primate model to specifically examine serum factors associated with impaired glucose regulation, at the time of impairment and two years prior to diagnosis.
Type 2 Pilot Projects
Treatment of Opioid Dependence in Drug Treatment Court
PI: Randall Brown, SMPH. Collaborators: Michael Fendrich, Michael Brondino, Lisa Berger, UW-Milwaukee; Joseph Bluestein, Madison Health Services; James Swartz, University of Illinois-Chicago.
The negative impact of substance abuse and misuse on public health and safety and individual and community well-being has been well-documented. “In one of the largest studies in the U.S., use of illicit drugs accounted for 500,000 emergency room visits, 1.3 million hospitalizations, and 39,000 deaths.” In order to turn the tide of this trend, we need to identify and support effective interventions for drug offenders that will significantly reduce drug use and its impact on personal and public health. This study will test a collaborative approach that introduces a “primary care” model into existing Drug Court interventions that, if successful, could be further tested and introduced in communities throughout WI to strengthen their existing drug court programs through work with primary care providers.
Treating Tobacco Dependence through Community Agencies
PI: Bruce Christiansen, SMPH. Collaborator: Kevin Reeder, the Salvation Army.
Great gains have been made in reducing the numbers of smokers in the U.S. but despite these reductions, tobacco use is still the primary cause of “preventable illness and premature death.” We also now know that of those who do still smoke, many have limited education and live in poverty. Because this population of smokers often has limited access to health insurance or primary care, it is more difficult to reach out to them to implement effective interventions. This study creates a partnership between the SMPH and the Salvation Army and its staff to implement a program that may have greater success in reaching these populations. If successful, this research may illustrate how other community-based agencies can be valuable partners in our efforts to reduce tobacco dependence.
Improving and Expanding Primary Care Treatment of Chronic Kidney Disease
PI: David A. Feldstein, SMPH. Collaborators: Jonathan B. Jaffrey, Richard E. Rieselback, SMPH; Thomas C. Gabert, Marshfield Clinic; Douglas A. Wiegmann, SOE; Linda B. Manwell, SMPH; Paul D. Smith, WREN.
Chronic Kidney Disease (CKD) is a worldwide epidemic with rapidly increasing rates in the United States and Wisconsin with significant impact on health care spending and quality of life. Early recognition and treatment of this disease can have significant health impacts, but often primary care physicians may not have access to the best available research evidence. This study will develop and test an internet-based electronic patient management tool (PMT) given to 20 primary care physicians (from the Wisconsin Network for Health Research/WiNHR, and the Wisconsin Research and Education Network/WREN) that will include a CKD guideline checklist, educational modules, and electronic access to a nephrologist for consultation. The goal of this research is to give primary care physicians effective tools to best address the needs of their patients with CKD.
Intervention for Adults with Obesity: Feasibility Study
PI: Sarah Khan, SMPH. Collaborators: David P. Rakel, Bruce Barrett, SMPH.
Obesity is at epidemic levels in the United States and in Wisconsin. While programs to address weight loss abound, this feasibility study will combine elements of exercise, nutrition and a mindfulness component that targets sustained behavior modification. In addition, the program designed for this study brings together for both development and implementation a team of experts including a primary care doctor, nurse practitioner, nutritionist, exercise instructor and a mindfulness instructor. Results from this research will help us learn more about how to craft and apply successful weight reduction and lifestyle modification programs.
Talking about Medication in Assertive Community Treatment
PI: Colleen A. Mahoney, UW School of Social Work. Collaborators: Betty A. Chewning, School of Pharmacy (SOP), Ronald J. Diamond, Mental Health Center of Dane County
Mental illness is a significant health issue for millions of Americans and has serious and widely-recognized implications for the individual dealing with the illness, their friends, family and the larger community. Within this population, medication management, in particular the risks of not taking medication, is a significant problem. Managing medication use has often been addressed by an approach called Assertive Community Treatment, designed to improve client medication adherence through assertive participation of a case manager/ACT provider. This study will look at patient-provider communication within this model and at how movement towards greater shared decision-making may impact medication management.
Authoritative Parenting: Could it Reduce Teen Weight?
PI: Susan Riesch, School of Nursing (SON). Collaborators: Bradford Brown, School of Education (SOE); Aaron L. Carrel, UW Pediatric Fitness Clinic; Carmen R. Valdez, SOE; Whitney P. Witt, SMPH.
Obesity in youth and adults has been linked to cardio-vascular disease, diabetes and hypertension among many other ailments that impact an individual’s quality of life and put a strain on our health care system. While there are many factors that can lead to childhood overweight and obesity, this study will look at the impact of parenting style on a child’s eating and exercise habits. Specifically, an interdisciplinary team of health, social and behavioral scientists will research, design and test an intervention for parents of overweight teenagers that focuses on setting firm and fair limits conveyed in an affectionate manner.
Optimizing Management of Ventilator-associated Pneumonia in the ICU
PI: Nasia Safdar, SMPH. Collaborators: Pascale Carayon, SOE; Kenneth E Wood, SMPH; Matthew C Hall, Marshfield Clinic.
Estimates suggest that as many as one hospital patient in ten acquires a nosocomial infection, otherwise known as a hospital-acquired infection, each year. The most common of these found in the intensive care unit (ICU) is called ventilator-associated pneumonia (VAP) with research showing that 10-20% of patients receiving over 48 hours of mechanical ventilation develop this pneumonia. This is of special concern to those critically ill patients who come to the ICU for whom the added burden of VAP can prove fatal. While national guidelines outline steps for diagnosing and treating VAP to improve patient health, not all ICUs follow these guidelines for reasons we do not yet fully understand. In partnership with the UW School of Engineering, the researchers hope to identify and understand barriers to the implementation of these guidelines…”[The] long-term goal is to improve adherence to the guidelines by developing methods to reduce barriers where possible and assist health-care workers in working around others.”
Utilizing Novel Interventions to Prevent Diabetes in Youth (UNITY)
PI: Eva Marie Vivian, SOP. Collaborators: Patricia Kokotailo, SMPH; Kenneth Loving, Access Community Health Center; Naomi Wedel, Dean West Clinic; Pamela Myhre, SON.
National reports have cautioned that one in three children born in the year 2000 would develop type 2 diabetes. According to the American Diabetes Association, Type 2 diabetes is more common in African Americas, Latinos, Native Americans and Asian Americans/Pacific Islanders and those with type 2 diabetes have a higher risk of heart disease, blindness, nerve and kidney damage. A vital component of treating type 2 diabetes is screening for and addressing this disease in younger populations. This research study is designed to determine if a community-based, family-centered diabetes prevention program with a peer component might increase the success rate of identifying teens with or at risk of developing type 2 diabetes and teach us more about some of the problems children and families face when trying to lead a healthy lifestyle.
Primary-Care Provider Barriers to Colon Cancer Screening
PI: Jennifer Weiss, UW Hospital. Collaborators: Patrick Pfau, Sally Kraft, Maureen Smith, Michael Lucey, SMPH.
Colorectal cancer (also called colon cancer or large bowel cancer) is the third most common form of cancer and the second leading cause of cancer-related death in the Western world. Current screening techniques that identify and remove the polyps that can turn into colorectal cancer are widely available and can decrease chances of death by up to 75-90%. However, there is significant variability in screening rates, even when health insurance coverage is not a barrier. This research pilot will survey primary care clinics and providers to better understand attitudes toward and training in colorectal cancer screening, cancer screening beliefs and practices and system-related issues to determine whether barriers to screening as seen by providers explain differences in rates of screening.
Improving Cardiac Surgical Care: A Work System Approach
PI: Douglas A. Weigmann, SOE, SMPH. Collaborators: Niloo Edwards, SMPH; Hope Maki, Marshfield Clinic; Thoralf Sundt, Mayo Clinic.
Heart surgery is one of the most common surgeries performed in hospital operating rooms (OR) and while we have witnessed significant improvement in survival rates over the past 50 years, there is still a great deal of variability in surgical outcomes across surgeons and across institutions. Whereas part of this variability can possibly be associated with individual surgeon skill, other factors may play a role as well. This research study will look at cardiac surgery from a “work systems” approach and try to identify and explain how other variables—such as staffing, equipment reliability, team familiarity, workload—contribute to surgical performance. “The long term goal of this research is to further improve cardiac surgical care by enhancing or re-engineering the surgical care process.”
Dian Land, (608) 261-1034, dj.land@hosp.wisc.edu
