Research Initiated September 2006

A Comprehensive Multidisciplinary Search for Biologic Predictors of Disease Progression in Chronic Lung Disease
Jesse Roman, M.D., Dean Jones, Ph.D., and Ken Brigham, M.D., Pulmonary Medicine, School of Medicine
Michael Kutner, Ph.D., Biostatistics, Rollins School of Public Health
Purpose: This institute will develop tools to assist in predicting which patients with chronic lung disease will show disease progression. This objective is considered important for three reasons. First, once identified, patients predicted to progress can be subjected to aggressive targeted interventions. Second, the identification of patients at risk for progression will help focus limited resources to those who are most likely to need them. Third, it is anticipated that research efforts in this arena will serve to identify novel cellular and molecular mechanisms involved in lung disease development and progression. This, in turn, will unveil new targets for the generation of novel strategies for therapeutic intervention. A multidisciplinary research program has been assembled that includes clinician-investigators, basic scientists, and biostatisticians from several components of the WHSC with the purpose of developing novel tools for predicting disease outcome in patients with lung disease.

A Pharmaco-Metabolomic Approach to Pain and Sleep Management
Kathy Parker, Ph.D., Adult and Elder Health, Nell Hodgson Woodruff School of Nursing
Marc Bouzyk, Ph.D., Human Genetics, School of Medicine
Raymond Dingledine, Ph.D., Pharmacology, School of Medicine
Purpose: A variety of factors have been proposed to account for the disturbed nocturnal sleep and daytime sleepiness so often observed in oncology patients. Cancer-related pain, a common and often inadequately treated symptom, is likely a major contributing factor. Although long considered to be the mainstay of pain therapy, opioid analgesics are also known to adversely affect nocturnal sleep quality and cause daytime sleepiness. Nonetheless, optimal treatment of both pain and sleep disturbances is essential for enhancing the functioning and well-being of these patients. The purpose of the proposed study is to help build a statistical model that will predict the best type of opioid, the most appropriate dose, and the optimal timing of opioid administration to maximize pain control and minimize sleep disturbances in an individual-an intervention based on pharmacogenetics and metabolomics.

Biomarkers of Brain Pathology: Identifying Increased Risks for Alzheimer's Disease and Drug Addiction with Mass Spectrometry
Mark Wilson, Ph.D., Sarah Pruett, Ph.D., Leonard Howell, Ph.D., and Lary Walker, Ph.D., Yerkes National Primate Research Center
Purpose: Proteomics and metabolomics represent the new frontier for translation research focused on interventional strategies to prevent or treat a number of pathologies affecting the brain, including neurodegeneration and drug addiction. Cutting-edge mass spectrometry is arguably one of the most important applications for protein and small molecular identification and quantification. This collaborative project, aligned to the objectives of the Predictive Health Institute, will use the analytic power of mass spectrometry to expand two existing research programs to develop new strategies and potential interventions to alleviate neurodegeneration and addiction and, in doing so, will establish proteomics and metabolomics capabilities with the Biomarkers Core at the Yerkes National Primate Research Center.

Bridging Immunology, Neuroscience , and Imaging: A New Strategy for Developing Vaccines and Therapeutics Against Neurologic Diseases
Rafi Ahmed, Ph.D., Emory Vaccine Center, Yerkes National Primate Research Center
Stuart Zola, Ph.D., Yerkes National Primate Research Center
Purpose: The goal of this institute is to explore the possibility of developing therapeutic vaccines against noninfectious diseases like Alzheimer's disease by applying what is known about immune system function to the development of therapeutics against brain-related neurodegenerative disorders. There is virtually no place else on the globe better suited to undertake this innovative challenge than right here, where there are world-class immunologists, neuroscientists, brain imaging scientists, and the resources of the Emory Vaccine Center/Yerkes National Primate Research Center.

Early Infancy Predictive Health Modeling: Biologic Marker Extraction, Identification, and Projection
Michelle Lampl, M.D., Ph.D., Amanda Thompson, MA, Anthropology, Emory College
Purpose: This project seeks to initiate the development of an Infant Predictive Health Panel to parallel the proposed Adult Predictive Health Profile, with attention to those developmental factors that have been suggested by previous work to predict adult health sequelae. The identification of infant health biomarkers can initiate an evidence-based clinical practice promoting healthy life-ways early on. The research work encompasses: (1) channeling existing extraction and assay methodology to predictive health practice, (2) identifying early risk profiles among healthy infants and contributing to an evidentiary base for health-promoting early life-ways, and (3) promoting collaboration among Emory resources to elevate practical application of existing and potential research to the benefit of the Health Sciences Center and its 2012 goal.

Establishing a Cancer Risk Prediction and Prevention Research Program at Emory University
Roberd Bostick, M.D., MPH. Epidemiology. Rollins School of Public Health
Purpose: This project proposes establishing a multidisciplinary Cancer Risk Prediction and Prevention Research Program at Emory that will draw together investigators from public health, medicine, basic science, engineering (at Emory and Georgia Tech), genetics, and biostatistics to work synergistically with the Predictive Health Institute and the Winship Cancer Institute. The focus of the new program will be on the development, validation, and application of biomarkers of risk for cancer. The development of the Cancer Risk Prediction and Prevention Research Program will begin with research projects on colorectal cancer, the second leading cause of cancer deaths in the U.S. among men and women combined, and on prostate cancer, the second leading cause of cancer deaths in men.

Evaluation of Patient Characteristics as Predictors of Acute Treatment Toxicity
Andre Rogatko, Ph.D., Biostatistics, Rollins School of Public Health, Winship Cancer Institute
Purpose: The goal of this institute is to construct a comprehensive model that integrates clinical, genetic, pharmacokinetic, and pharmacodynamic information to provide guided dose selection. It is expected that the information gathered during this study will allow the customization of dosing regimens, wherein taxane doses are adjusted according to individual patient susceptibilities. Hence, each patient would be maintained at his or her maximum tolerable dose and duration of therapy, thus reducing the number of patients who are underdosed (reduced efficacy), or overdosed (unacceptable toxicity). The Woodruff Fund has been effectively funding pilot studies that create preliminary data for subsequent successful federal research projects. The proposed pilot study would generate preliminary data for an ensuing larger study that will be the first large-scale effort to link genetic, pharmacokinetic, and clinical variables for the prediction of toxicity and response to taxane-based chemotherapy. This project aims to acquire detailed patient information prospectively to identify prognostic factors and patient characteristics predictive of toxic response to taxane-based chemotherapy.

Genetic Databank for Cardiovascular Disease and Stroke: Investigation of the Genetic Basis of Oxidative Stress, Vascular Dysfunction, Cardiovascular Disease, and Stroke
Arshed Quyyumi, M.D., A. Aziar Zafari, M.D., Ph.D., Viola Vaccarino, M.D., Ph.D., and David Harrison, M.D., Cardiology,School of Medicine
Purpose: Cardiovascular disease (CVD), including stroke, continues to be the principal cause of death in developed countries. The cost of the disease is high in terms of morbidity, mortality, and its financial burden on health care systems. Moreover, ethnicity-based CVD health disparities appear to be common, with the prevalence of diabetes, hypertension, obesity, and CVD events being greater in African Americans compared with their Caucasian counterparts. The aim of this proposal is to establish an adequately powered database of patients who will be phenotyped for both sub-clinical and clinical disease and risk biomarkers, and will be followed up to determine prospective outcomes free of CVD and neurologic events. This database will enable Emory scientists in cardiology, neurology, human genetics, biomarker laboratories, and other departments to compete for independent funding for detailed genomic analyses.

Making a University He althy by Understanding its Health Care
Kenneth Thorpe, Ph.D., Benjamin Druss, M.D., PHD, Kimberly Rask, M.D., Ph.D., Health Policy and Management, Rollins
School of Public Health
Purpose: A university is a unique form of institution - an employer, a generator of new knowledge, and, for those with academic medical centers, a provider of health care. Although medical and public health researchers commonly study health and health care, there have rarely been systematic efforts to turn the lens back and understand the health and wellbeing of our own universities. In part, this has reflected limitations shared by all large employer-purchasers, who typically provide insurance through multiple carriers and separate health, mental health, and pharmacy data. Analysis of such data also has been limited by appropriate concerns for maintaining the privacy of university employees. Emory's new Management Service Organization, which merges data across these different insurers and creates a deidentified data base, makes it possible for the first time to track care across those different silos while preserving employee confidentiality. It provides a unique opportunity to advance scientific knowledge, as well as to understand and improve care within the Emory community. This initiative will explore how these data can be used for population-based research at Emory.

Identify Method of Detec tion and Control of Cytomegalovirus Congenital Disease
Edward Mocarski, Microbiology and Immunology, School of Medicine
Purpose: Cytomegalovirus (CMV) remains the major infectious cause of progressive hearing damage in newborns. This project proposes to assemble a working group of investigators to address viral pathogenesis and host immune response determinants that control susceptibility to CMV congenital disease. The aim is to design a program that will investigate natural patterns of infection and protection from disease in order to establish appropriate methods of detection, targets for vaccination, and approaches to therapeutic intervention.