Medical Education and Research Committee New Investigator Program Grants Awarded
The following New Investigator Program grants have been awarded by the Wisconsin Partnership Program's Medical Education and Research Committee:
2008 Awards
Positron Emission Tomography Imaging of Tumor Angiogenesis
Weibo Cai, PhD, Department of Radiology
Award: $90,000
The principal investigator aims to create new Positron Emission Tomography (PET) scan markers that will allow radiologists to create personalized therapy to attack tumors. Cai wants to create molecular imaging agents that will target a protein important for cancer progression.
The new method will help identify patients who can benefit from a particular type of therapy, and guide the administration of the right drug at the right time. PET scans will show doctors whether the therapy is working. This "personalized medicine" approach will also have applications in diseases such as heart attack and stroke.
Genetic and Environmental Predictors of Serum Levels of 25-Hydroxyvitamin D
Corinne D Engelman, MSPH, PhD, Department of Population Health Sciences
Award: $90,000
The principal investigator will use data from 300 people enrolled in the Survey of Health in Wisconsin (SHOW), which is also funded by the Wisconsin Partnership Program, to check vitamin D levels of people of different skin colors and from different environments.
Vitamin D is critical for health, and low levels in the blood are associated with bone disease, cancer, autoimmune diseases, infectious diseases, and type 2 diabetes. Sunlight absorbed through the skin is an important source of vitamin D, yet there is little data on how skin color and genetics effect levels of vitamin D in the blood.
Computed Tomography (CT) with Reduced Radiation Dose Using Prior Image Constrained Compressed Sensing (PICCS) Reconstruction
Christopher J Francois, MD, Department of Radiology
Award: $90,000
The principal investigator will test a technique invented at the University of Wisconsin School of Medicine and Public Health that could reduce the radiation dose needed for Computed Tomography (CT) by 90 percent or more.
While CT scans have revolutionized the practice of medicine in the past 40 years, there is growing concern over the radiation exposure to patients from these examinations. Since more than 60 million CT scans are given every year in the United States, the technique could improve health care for many people, especially coronary patients undergoing angiography and pediatric patients.
Evaluation of Cuidandome: A Communitywide Intervention to Promote Breast & Cervical Cancer Screening among Latinas
Ana P Martinez-Donate, PhD, Department of Population Health Sciences
Award: $90,000
The principal investigator will study the effectiveness of Cuidándome, a community program that promotes breast and cervical (BCC) screening among Latinas in Dane County. Cuidándome combines small-group education, a media campaign, and cultural-competency training for health care providers.
This study will also estimate BCC screening rates among Latinas in Dane County and identify factors that contribute to Latinas' underuse of BCC preventive services. Results will shape future programs, with the goal of reducing BCC cases and deaths in this underserved population.
2007 Awards
Falls Risk Detection and Gait Instabilities in Older Adults
Bryan Heiderscheit, PhD, Assistant Professor, Department of Orthopedics & Rehabilitation
Award: $100,000 over two years
About 30 percent of adults over 65 years old fall each year. In Wisconsin alone, annual medical care costs due to fall-related injuries were reported at $96 million. Arguably of greater concern, Wisconsin's death rate due to falls is twice the national average. This project will seek to develop an accurate measure of falls risk status among older adults, which is easily used in the clinics. This measure will improve the identification of individuals at risk of falling and facilitate the proper treatment interventions.
Reconstructing HIV Sequence Histories to Identify Potent Immune Responses
David O'Connor, PhD, Assistant Professor, Department of Pathology and Laboratory Medicine
Award: $99,620 over two years
More than 40 million people are living with HIV/AIDS, including nearly 6,000 in Wisconsin. Developing an effective vaccine to prevent HIV transmission is an urgent public health priority. Vaccine strategies that work against other diseases have largely failed against HIV. The proposal's goal is to use virus archived within long-lived cells to pinpoint highly potent immune responses present only during the first weeks of an infection, which could be included in future HIV vaccines.
A New Diagnostic Test to Monitor Regression and Recurrence of Epithelial Ovarian Cancer
Manish Patankar, PhD, Assistant Professor, Department of Obstetrics and Gynecology
Award: $98,738 over two years
Ovarian cancer is the fifth leading cause of cancer-related deaths in the United States; about 300 women die from epithelial ovarian cancer in Wisconsin each year. There is a high mortality associated with this disease because in most women, the cancer is detected in advanced stages when treatment options are limited. Even after the bulk of the tumor is removed by surgery and chemotherapy, the disease generally recurs.
This proposal seeks to develop a novel diagnostic test that will help identify disease recurrence at a much earlier stage than currently possible. Successful development of such a test will lead to more efficient treatment of recurring ovarian cancer.
Metabolic Control of Metastasis by a Master Regulator of Neurogenesis: Molecular Mechanisms and Therapeutics
Avtar Roopra, PhD, Assistant Professor, Department of Neurology
Award: $99,990 over two years
Breast cancer is the most commonly diagnosed cancer in the female population of Wisconsin and ranks as the second most common cause of cancer mortality. Greater than 90 percent of breast cancer mortalities are due to metastasis of the primary tumor. A therapeutic regimen that successfully prevents metastasis has the potential to save about 800 lives per year in Wisconsin. This proposal will test the hypothesis that simply regulating sugar metabolism and diet can be used to control metastasis.
Probiotics for prevention of infection by multiresistant bacteria
Nasia Safdar, MBBS, Assistant Professor, Department of Medicine
Award: $100,000 over two years
Multidrug-resistant bacteria are a major cause of severe infections in health care institutions in the United States, and their containment has been deemed a public health priority. This proposal will study the use of a probiotic (dietary supplement) preparation in hospitalized patients as a new means of preventing infection by drug-resistant bacteria.
The Relationship between Asthma and Obstructive Sleep Apnea (OSA) — A Pilot Study of the Effects of Treatment for Comorbid OSA in Patients with Asthma
Mihaela Teodorescu, MD, Assistant Professor, Department of Medicine
Award: $99,995 over two years
Asthma represents a significant public health burden. In 2002, almost 80 percent of the 450,000 people with asthma in Wisconsin reported symptoms in the prior 30 days. Many asthmatic individuals report sleep disturbances and an unexpectedly high prevalence of obstructive sleep apnea (OSA) was found in patients with severe asthma.
Furthermore, treatment of OSA with continuous positive airway pressure (CPAP) improved asthma control. This project will study prevalence and predictors of OSA symptoms in asthma patients, and the impact of treatment with CPAP for OSA on asthma control, sleep and quality of life, and health resources utilization.
2006 Awards
Determinants of Antibiotic Resistance in Nursing Homes
Christopher Crnich, MD, MS, Assistant Professor, Department of Medicine
Award: $100,000 over 18 months
Infections from antibiotic-resistant bacteria are an increasing cause of illness and death among residents of nursing homes. This community-based longitudinal study of residents in 12 facilities will help establish the extent of antibiotic resistance in Wisconsin nursing homes.
The information gained from this study will help in the design of future studies that will examine the impact that environment and systems of care have on the spread of antibiotic-resistant bacteria in nursing homes. Ultimately, this information will be used to develop and test systems-based interventions to reduce the illness and death associated with these types of infections.
Treatment of Vitamin D Insufficiency
Karen Hansen, MD, Assistant Professor, Department of Medicine
Award: $100,000 over two years
Human skin makes vitamin D from exposure to sunlight. Because of little sun exposure, many people living in Wisconsin have low vitamin D levels, which can contribute to weak bones. This study will assess whether vitamin D tablets can increase calcium absorption in older women, thereby leading to stronger bones.
Partnering with Quit lines to Promote Youth Smoking Cessation in Wisconsin
Tammy Harris Sims, MD, MS, Assistant Professor, Department of Pediatrics
Award: $100,000 over two years
Tobacco use is the leading preventable cause of illness and death in the United States, and about 80 percent of smokers become daily smokers before age 20. Although the origins and motivations for tobacco use are found in youth, assessments and interventions are largely developed for adults. This project will evaluate the effectiveness of an age-appropriate telephone counseling intervention in helping adolescent and young adult smokers quit.
Creation of a Bovine Cryptosporidium Vaccine to Reduce Outbreaks in Human Populations
Laura Knoll, PhD, Assistant Professor, Department of Medical Microbiology & Immunology
Award: $100,000 over one year
Cryptosporidium is well-known for causing water-borne outbreaks of diarrhea, as in the spring 1993 contamination of the Milwaukee city water supply that caused illness in more than 400,000 people. Similarly, cryptosporidium is a frequent and serious pathogen of young calves, decreasing their growth rate and increasing the costs to dairy farms. The goal of this project is to develop a cryptosporidium vaccine for cattle both to protect dairy farms and to eliminate cow to human transmission of cryptosporidium.
Integrating Variation at Single Nucleotides and Short Tandem Repeats to Identify Genetic Associations with Complex Diseases
Bret Payseur, PhD, Assistant Professor, Department of Genetics
Award: $100,000 over two years
A powerful approach to identifying the genes that cause human disease is to associate disease with DNA markers in large populations. This project will compare two different types of DNA markers commonly used by researchers, which will help clinical scientists decide which type of marker is best for their particular study. Additionally, this project will develop new methods for associating markers with disease.
Magnetic Resonance Imaging in a Study of Prolotherapy for Knee Osteoarthritis
David Rabago, MD, Assistant Professor, Department of Family Medicine
Award: $99,971 over two years
Knee osteoarthritis is a common, painful, debilitating, age-related condition. MRI is recognized as the best way to view the knee; however, the MRI assessment of the entire knee can take up to one hour. This study will compare the standard MRI technique to a new, five-minute, less expensive MRI technique to determine if both methods can provide similar assessment of the knee.
Surface-Rendered 3D MRI Overlaid Into Live X-Ray Fluoroscopy to Guide Endomyocardial Progenitor Cell Therapy for Recent Myocardial Infarction: Technical Development and Validation Toward Clinical Translation
Amish Raval, MD, Assistant Professor, Department of Medicine
Award: $100,000 over two years
Patients who suffer heart attack often develop heart enlargement, congestion and heart failure. Injection of adult stem cells into damaged heart muscle may prevent complications of a heart attack; however, catheter techniques are limited by poor imaging technology. This project will develop a novel image guidance system using computer hardware and software components to combine MRI and X-Ray images to allow researchers to more clearly visualize heart attack sites during stem cell injection.
2005 — First Cycle Awards
Healthy Children, Strong Families – Supporting Caregivers in Improving Lifestyles
Alexandra Adams, MD, PhD, Department of Family Medicine
Award: $93,054 over two years
This project builds on a study of childhood obesity in three Wisconsin Native American tribes by evaluating metabolic and behavioral changes in the adult primary caregivers of American Indian children. By engaging the parents in behavior changes that will benefit themselves as well as their children, this study will allow researchers to determine whether a family-based intervention is an effective method for changing behavior in adult caregivers. Endocrinology fellow Deb Wubben, MD, MPH, will also be working on the project.
Investigating Fungal Infection: Analysis of Spores From the Human Fungal Pathogen Cryptococcus Neoformans
Christina Hull, PhD, Department of Biomolecular Chemistry and Medical Microbiology and Immunology
Award: $100,000 over two years
Often, fungal growth and development result in the production of spores that can disperse into the environment, be inhaled by humans and germinate in the lungs. C. neoformans is a yeast-like fungus that usually causes only minor respiratory disease but can also disseminate to the central nervous system and produce a fatal form of meningitis. The goal of this project is to understand the properties of fungal spores that allow them to infect humans and cause disease.
Molecular Analysis of the Putative Mammalian siRNase ERI-1
Scott Kennedy, PhD, Department of Pharmacology
Award: $100,000 over two years
RNA interference takes advantage of a naturally occurring process to degrade RNA, the intermediary translator between the DNA of genes and the protein molecules they encode. By degrading RNA, genes can be "turned off." Initial successes using RNA interference to target cancer genes have generated excitement that this technology may eventually be used to treat human disease.
The project will increase knowledge of RNA interference and how the process is regulated. It may identify drug targets that eventually will allow physicians to use RNA interference as a therapy in a wide spectrum of diseases.
Sterol Carrier Protein 2 is a Novel Link Between Aging and Alzheimer's Disease
Luigi Puglielli, MD, PhD, Department of Medicine
Award:$100,000 over two years
This project seeks to identify new molecular links between aging, Alzheimer's disease and cholesterol metabolism. Sterol carrier protein-2 is a small protein that is highly expressed in the brain, can function as a cholesterol carrier and is activated in an age-dependent fashion.
Since intracellular cholesterol metabolism and distribution can regulate the rate of amyloid â-peptide generation, the first molecular step in the development of Alzheimer's disease, understanding more about sterol carrier protein 2 may shed new light on the pathogenesis of Alzheimer's disease.
Novel Therapies Against Influenza Infection
Stacey Schultz-Cherry, PhD, Department of Medical Microbiology
Award: $100,000 over two years
Two of limitations to the existing flu vaccine are that the vaccine does not work effectively in high-risk groups, such as the elderly, and the virus changes every year, requiring the development of new vaccines annually. Blocking viral replication with novel antiviral peptides that attack all strains of influenza virus may be a way to address those limitations. The goals of this project are to understand how antiviral peptides regulate viral growth, and how these peptides may be used in preventing and treating influenza infection in young and aged animal models.
Molecular Mechanism of Lung Organogenesis, Tumorigenesis and Asthma
Xin Sun, PhD, Department of Medical Genetics
Award: $100,000 over two years
The long-term goal of this research is to establish the genetic bases for devastating lung diseases such as Respiratory Distress Syndrome, lung cancer and asthma. Researchers on this project expect to use a combination of advanced genomic and genetic approaches to uncover gene function related to the development of the lung and diseases that affect it.
2005 — Second Cycle Awards
The Role of Ikaros in Cellular Proliferation
Sinisa Dovat, MD, Assistant Professor, Department of Pediatrics
Award: $100,000 over two years
This project focuses on identifying proteins controlling cellular proliferation with the goal to use these results to design a better treatment for leukemia and other forms of cancer. Specifically, this project will study the role of the Ikaros protein, a known tumor suppressor, in the response to radiation-induced DNA damage.
Topical Honey for Diabetic Foot Ulcers
Jennifer Eddy, MD, Assistant Professor, Department of Family Medicine
Award: $99,976 over two years
More than 10 million people in the United States have diabetes; about 15 percent of those patients will develop ulcers of the lower legs or feet, sometimes requiring amputation. Honey has been used as a treatment for millenia, and medical reports suggest that it may contribute to healing in human and animal wounds. This project is a pilot study of the use of honey to treat diabetic foot ulcers.
Cellular and Viral Determinants of Human Cytomegalovirus Lytic and Latent Replication Cycles
Robert Kalejta, PhD, Assistant Professor, Department of Oncology
Award: $100,000 over two years
Human Cytomegalovirus (HCMV) is a virus that infects most children, and usually remains dormant in the body for life. However, the virus can be re-activated, and has been implicated in a number of human diseases. Currently, there is no vaccine for HCMV. The research in this project will help to determine how HCMV infects people, how the dormant virus is re-activated, and will also help to identify targets for drugs to treat this infection.
Androgen Receptor as an Immunological Target for the Treatment of Prostate Cancer
Douglas McNeel, MD, PhD, Assistant Professor, Department of Medicine
Award: $99,906 over two years
Prostate cancer is the second leading cause of cancer-related death in men in the United States. New therapies are needed to reduce the numbers of people dying from this disease. This project will study the possibility of developing vaccines as a treatment for prostate cancer.
Wnt/Frizzled Signals in Normal and Malignant Lymphoid Development
Erik Ranheim, MD, PhD, Assistant Professor, Department of Pathology & Laboratory Medicine
Award: $100,000 over two years
This research studies the cells involved in leukemia, and is aimed at understanding the pathways by which normal cells in the immune system develop and how that process might be abnormally turned on in leukemia.
Novel Exploratory Approaches to Elucidating the Role of GRAIL in CD25+ T Regulatory Cell Biological Function
Christine Seroogy, MD, Assistant Professor, Department of Pediatrics
Award: $91,560 over two years
CD25+ T regulatory cells are important in modifying immune responses in varied human disease states, ranging from allergies to autoimmune diseases to rejection of transplanted organs. How this subset of T cells restores balance to immune responses remains poorly defined. By studying the biological mechanisms of the CD25+ T cells, important contributions can be made to therapeutic approaches for many human diseases.
GLI2 Protein Stabilization in the Activation of Hedgehog Signaling Pathway in Prostate Cancer
Vladimir Spiegelman, MD, PhD, Assistant Professor, Department of Dermatology
Award: $100,000 over two years
Prostate cancer is the second leading cause of cancer-related death in men in the United States. There is poor understanding of the biological pathways that lead to prostate tumor development. This project will study the Hedgehog signaling pathway, with the ultimate goal of identifying targets for drugs for prostate cancer prevention and treatment.
Optimizing Immunuppressant Therapy Based on Viral Genetics to Improve Hepatitis C-Infected Transplant Patient Outcomes
Rob Striker, MD, PhD, Assistant Professor, Departments of Medicine and Medical Microbiology & Immunology
Award: $100,000 over two years
Hepatitis C Virus (HCV) is a major cause of liver disease worldwide, and the most common reason for liver transplant and retransplant in the United States. Clinical studies have shown that some immunosuppressant drugs can improve the outcomes for HCV infected patients, but there is no consensus about the optimal drug therapy. This project will allow development of molecular diagnostics to tailor immunosuppressant therapy to the specific HCV strain infecting a patient.
Effects of Statin Therapy on Vascular Properties and Outcomes in Diastolic Heart Failure Patients
Nancy Sweitzer, MD, PhD, Assistant Professor, Department of Medicine
Award: $100,000 over two years
Diastolic heart failure is a form of heart failure occurring most commonly in the elderly and in women. There are no established treatments for this disease. Although it has long been thought that abnormalities of heart function are responsible for the disease, it is increasingly apparent that there are abnormalities of the blood vessels in many of these patients which may contribute to development of diastolic heart failure. This study is a pilot clinical trial to test the effect of statin drugs on blood vessel properties, symptoms and disease progression in patients with diastolic heart failure.
Mechanisms of CREB regulation and function in response to DNA damage
Randal Tibbetts, PhD, Assistant Professor, Department of Pharmacology
Award: $100,000 over two years
Genomic instablity resulting from unrepaired DNA damage is a root cause of human cancer development. The ATM gene plays a critical role in suppressing genomic instability. This project will study ATM function, and promises to yield new insights into how cells respond to DNA damage and how cancer arises.