Study of Biomarkers of Oxidant Stress as Predictors of Health and
Disease Risk Wayne Alexander, M.D., Ph.D., Department of Medicine, School of Medicine Purpose: To initiate a longitudinal study that examines the
relationship between oxidant stress and cardiovascular disease
Initiated September 2005
Behavioral-Genetic Prediction of Risk for Schizophrenia
in Children J. F. Cubells, M.D., Ph.D., Genetics and Psychiatry, School of Medicine Purpose: This project seeks to develop both molecular genetic and cognitive/behavioral
predictors of psychotic illness in
children with the 22q11 deletion syndrome (22q11DS). Such children are at
statistically very high risk for schizophrenia
and other psychotic disorders. A major goal of the work is to generate preliminary
data to support competitive applications
for federal funding of a large, long-term, longitudinal follow-up of children
with 22q11DS.
Biomarker Assessment of Metabolic and Vascular Risk Larry Phillips, M.D., Department of Medicine, Endocrinology, School of Medicine Purpose: Advances in medical science have led to therapies for common disorders
such as diabetes, hypertension, and
dyslipidemia, which confer major morbidity, mortality, and cost, but current
treatment can be provided only once the
disorder has been recognized—often after complications have already
begun—and cannot restore normal tissue and organ
function. In order to improve health, the disorders must be recognized when
treatment is more efficacious and more costeffective;
it would be ideal to identify patients at risk earlier in their natural histories,
when mechanism-based therapies
might be able to prevent loss of function. This predictive health project
will test the hypothesis that profiling oxidative
stress and inflammatory biomarkers will permit prediction of deterioration
of metabolic and vascular function prior to the
development of clinical disease.
Economic, Epidemiologic, and Behavioral Research Kimberly Rask, M.D., Ph.D., Health Policy and Management,
Rollins School of Public Health Purpose: The purpose of this study is to explore the feasibility of including
economic, epidemiologic, and behavioral risk
factors in predictive health models, using the specific example of patients
with type II diabetes, a common chronic disease.
This project will use a national population-based survey and a pilot study
at an Emory-affiliated clinical setting to (1) collect
a comprehensive set of biologic, behavioral, and environmental risk factors
likely to affect an individual’s health status
and (2) explore the effectiveness of modifying selected risk factors, including
health behaviors in persons at high risk of
developing a clinical diagnosis of type II diabetes.
The clinical focus of this project has been broadened beyond hypertension
to include a constellation of diseases that
affect patients with diabetes. These diseases share both behavioral and biologic
risk factors and pathways, providing a useful
model for evaluating the potential impact of personalized health interventions
for chronic health conditions.
Inflammation and Predictive Medicine David Stephens, M.D., Department of Medicine, Infectious Diseases, School of Medicine
Cornelia Weyand, M.D., Ph.D., and J. Goronzy, M.D., Ph.D., Department of Medicine, Lowance
Center, School of Medicine
Rafi Ahmed, Ph.D., Microbiology and Immunology, School of Medicine Purpose: The goal of this project is to identify novel and feasible
approaches that integrate exciting new fundamental
discoveries at Emory and elsewhere in inflammation and immunity with predictive
health. Specifically, the goal is to integrate
new quantitative immune methodologies and discoveries into predictive health,
to engage multidisciplinary science
(genetics, biochemistry, bioinformatics, engineering, microbiology and human
immunology, biostatistics and analytical
epidemiology, behavioral research, economics, population biology, and clinical
medicine) in addressing significant and
complex problems in immune dysfunction and to develop strategies for acceptance
and use of immunology and immune
activation markers in predictive health.
Predictive Algorithms of Parkinson’s Disease Gary Miller, Ph.D., and Scott Bartell, Ph.D., Environmental and Occupational
Health, Rollins School of Public Health Purpose: The goal of this project is to develop models
to predict Parkinson’s disease. The strategy includes taking advantage
of a wide collection of data, including epidemiologic, basic science, and
clinical, to generate algorithms to identify
individuals at greater risk of developing Parkinson’s disease. Identification
of high-risk individuals will allow for early
intervention designed to prevent or slow the progression of the disease.
Predictive Treatment for ALS (Lou Gehrig’s disease) Jonathan Glass, M.D., Neurology, School of Medicine Purpose: Approximately 10% of people with ALS inherit the
disease directly from their parents. The most common
known cause for this familial form of ALS (fALS) is a mutation in the gene
superoxide dismutase 1 (SOD1), which accounts
for about 20% of familial cases. Animals engineered to carry human SOD1 mutations
develop ALS. Therapeutic
interventions with a variety of drugs in these animals have shown positive
effects on disease onset or progression, but none
of these agents has shown efficacy in humans with non-familial forms of ALS.
This project proposes to identify the population
“at risk” for fALS in order to design a clinical trial to delay
the onset or prevent ALS. Specifically, people harboring
a mutation in SOD1 have a high likelihood of dying of ALS, and this target
population, though small, will be ideal for
testing some of the same agents that have been effective in SOD1 mutant animals.
Profiling Protein Expression in Gynecologic Tumors by Protein Arrays R. P. Huang, M.D., Ph.D., Gynecology and Obstetrics, School of Medicine Purpose: Protein arrays have emerged as a technology to
study protein expression and protein function in a highthroughput
manner. One of the obvious applications of protein arrays is to profile protein
expression in a patients’ specimen.
Through identification of unique biomarkers or biosignatures, antibody arrays
may have great impact on predictive
and personalized medicine. The purpose of this work is to establish a program
for the application of antibody array
technology in predictive and personalized medicine using cancer as example.
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.
* Supported by the Robert W. Woodruff Health Sciences Center Fund
Initiated September 2007
Accelerated Biological Aging as Shared Mechanism in Cardiovascular and Brain Disorders Viola Vaccarino, M.D., Ph.D., Cardiology, School of Medicine
Investigation of the Environmental and Genetic Basis of Non-Alcoholic Fatty Liver Disease through the Emory NAFLD Research Group: A Multidisciplinary Project Uniting Liver Experts Diego Martin, M.D., Ph.D. Radiology, School of Medicine Miriam Vos, M.D., Pediatrics, School of Medicine
Large Scale Genome Resequencing at Emory: Revolutionizing Basic and Clinical Research Stephen T. Warren, Ph.D. and Michael Zwick, Ph.D., Department of Human Genetics. School of Medicine Purpose: This initiative provides support to establish "next generation" deep genomic resequencing at Emory. Using novel technologies developed at Emory along with a Solexa resequenicing instrument, generation of 1 billion basepairs of DNA sequence of targeted genomic intervals is possible in a matter of days at a cost of less than 0.0005¢ per base. Thus detecting sequence variation in a 1,000 candidate genes in patients with a particular disorder will be possible.
The Predict ALS (Lou Gehrig's disease) Study. Michael Benatar MBChB, M.S., DPhil, Neurology, School of Medicine Purpose: Amyotrophic lateral sclerosis (ALS), like many other neurodegenerative diseases, is characterized by a pre-symptomatic phase during which neuronal degeneration proceeds prior to the appearance of clinically manifest disease. This observation may explain, at least in part, the failure to identify therapeutic agents in clinical trials involving subjects with relatively advanced symptomatic disease. The goal of this project is improve our understanding of the pre-symptomatic phase of the disease and thereby perhaps to pave the way for a preventive clinical trial or a treatment trial of symptomatic subjects at an earlier stage of the disease. This study will involve the prospective and serial evaluation (using multiple investigative modalities) of a population of healthy individuals at risk for developing ALS based on the presence of a mutation in the superoxide dismutase (SOD1) gene.
Establishment of a Non-Human Primate Stroke Imaging Research Program Timothy Duong, Ph.D., Neurology and Yerkes Primate Research Center, Jacques Dion, M.D., Radiology, School of Medicine Stuart Zola, Ph.D., Yerkes Primate Research Center Purpose: Stroke is the third leading cause of death and the leading cause of long-term disability in the world. In the United States alone, 4.5 million people have permanent neurological deficits associated with stroke, 71% of stroke survivors can't return to work, and $57.9+ billion per year will be expended on stroke care. The cost is steadily rising because the conditions that put people at risk for stroke (such as heart disease and obesity) are also currently on the rise. At the heart of the issue to be addressed here is the fact that while numerous neuroprotective drugs have shown positive results on experimental rodent models of stroke, none has proven to be effective clinically, even after nearly three decades of research. One widely accepted view to account for this disappointing outcome is that the rodent stroke model simply does not adequately reflect the complexity and the dynamics of human stroke. Recent failures of several high profile neuroprotective drugs in Phase III clinical trials further underscore the importance of developing adequate animal models for stroke research. The Stroke Therapy Academic Industry Roundtable (STAIR), a national committee commissioned by the American Heart Association and the NIH, has recommended that clinically relevant non-human primate stroke models be established for developing and assessing neuroprotective drugs. With these facts in mind, we propose to leverage existing expertise and strengths at the Yerkes Center, Woodruff Health Sciences, Emory University, to establish a multi- and inter-disciplinary stroke research program based around clinically relevant non-human primate stroke models paired with innovative high-resolution brain imaging technology.
