ICTR Awards Clinical and Translational Pilot Grants

MADISON - The Institute for Clinical and Translational Research (ICTR) at UW-Madison recently awarded 22 pilot grants (listed below) for innovative 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 Dr. Marc K. Drezner, 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. Comprising 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 a particular protein, Ikaros. Clarifying 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 development of birth defects of the eye. Identifying the parts of the human genome that undergo duplication or deletion in affected people will help develop 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) show memory problems without functional difficulties. Nonetheless, those with aMCI who also lack awareness of memory decline (termed 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 certain 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 theorize that estrogen plays a role in the cross-talk between sensory innervation and the skeleton. Spelling out 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 percent 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), the mysterious deterioration 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 nerve-cell 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 brain injury from blocked blood flow. Specifically, they will examine the role of certain proteins in cytotoxic edema formation after nerve tissue resumes getting a blood supply following ischemia. The unique use of real-time MRI will identify biomarkers of brain injury and the potential therapeutic use of certain chemicals.

Respiratory Impairment and Recovery in Myelin Disorders
PI: Rebecca Johnson, SVM. Collaborators: Ian Duncan, Gordon Mitchell, SVM; John Fleming, SMPH

Breathing problems are a common symptom of myelination disorders such as multiple sclerosis (MS). Despite the life-threatening nature of these complications, little is known about how demyelination impairs breathing and the impact of non-invasive interventions that aim to improve breathing. Using a well-characterized rat model system, this project will provide the foundation for studies of respiratory insufficiency and 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.. 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 way 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 can predict 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 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 proteins found in plasma with those found following the removal of polyps. 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 preventive treatment, and will also shed light on how the disease develops.. This study will use a primate model to specifically examine serum factors associated with impaired glucose regulation.

Type 2 Pilot Projects

Treatment of Opioid Dependence in Drug Treatment Court
PI: Randall Brown, SMPH. Collaborators: Michael Fendrick, 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." This study will test a collaborative approach that introduces a "primary care" model into existing Drug Court interventions. If successful, the approach could be further tested and introduced in communities throughout the state 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

While great gains have been made in reducing the number of smokers in the U.S, tobacco use is still the primary cause of preventable illness and premature death. Of those who still smoke, many have limited education and live in poverty. Because this population 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 helpful in reducing 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 and 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) so primary care physicians can 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 a team of experts including a primary care doctor, nurse practitioner, nutritionist, exercise instructor and a mindfulness instructor. Results will reveal information 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. Within this population, medication management, in particular the risks of not taking medication, is a significant problem. This study will look at patient-provider communication within a particular treatment model and at how movement towards greater shared decision-making may affect 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 cardiovascular disease, diabetes and hypertension among many other ailments. This study will look at the impact of parenting style on a child's eating and exercise habits. Specifically, a 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 every year, as many as one hospital patient in ten acquires an infection during hospitalization.. The most common of these found in the intensive care unit is called ventilator-associated pneumonia (VAP). In partnership with the UW School of Engineering, the researchers hope to identify and understand barriers to the implementation of national guidelines to improve these patients' health

Using 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. 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 family-centered diabetes prevention program based in the community and with a peer component, might increase the success rate of identifying teens with or at risk of developing type 2 diabetes.

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 90 percent. However, screening rates vary greatly, 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.

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 survival rates overall have greatly improved over the past 50 years, there is still a great deal of variability in surgical results among surgeons and institutions. 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.

 

Date published: 7/25/2008