Center on Early Life Origins
of Disease
Xiaobin Wang, MD, MPH, ScD
Zanvyl Krieger Professor
Director
Center on the Early Life Origins of Disease
Johns Hopkins University
Department of Population, Family, and
Reproductive Health
Center on Early Life Origins of Disease
Mission
Research natural history, etiology, and early life
precursors of common and important health
problems in across the life span
Translate scientific discoveries in clinical and
public health settings: early prediction and
prevention, and personalized medicine
Educate and Train a new generation of child
health interdisciplinary and transdisciplinary
researchers and future leaders
Major Emphasis of the Center
•
Diseases of major clinical and public health significance
•
A life course approach and longitudinal cohorts
•
Integration of multi-level-dimension-factors
•
Bridge social behavioral science with biomedicine
•
Collaboration within and cross departments and schools
•
Ultimate Goal: to translation our research findings to
•
clinical and public health practice in order to meet the
needs of 21st century medicine and public health
Prospective Study Cohorts
Boston Birth
Cohort
Chinese Twin
Cohort
Chicago Family
Cohort
8,000 mother-infant
pairs
(~2,500 preterm)
2,000 twin pairs
MZ: DZ ratio 1:1
6 years and older
Over 1,000 families
Biological parents and
children 0-21 yr
Enrolled at Birth
F/U at pediatric
primary care visits
Baseline
6 yr follow-up
Baseline study
completed
Inner city, minority
(65% blacks)
in Boston
Homogeneous
Rural Chinese
White, suburb
In Chicago
4
Research Focus
Ongoing:
• Prematurity: 12.5% of babies
• Obesity: 20 to 40% of children & adults
• Asthma: 10 to 20% of children & adults
• Food allergy: 5 to 10% of children
• Early life Origins of adult diseases:
Cardiovascular diseases; Prediabetes,
Diabetes; Metabolic syndrome;
Osteoporosis
Future growth areas:
• Neuro-developmental outcomes
• Behavioral outcomes
Emerging Science: Early Life Origins
of Health and Disease
Great challenge and
opportunity for all of us:
Coronary heart disease, type 2
diabetes, breast cancer and
many other chronic diseases
are unnecessary. Their
occurrence is not mandated by
genes passed down to us
through thousands of years of
evolution. Chronic diseases
are not the inevitable lot of
humankind. They are the result
of the changing pattern of
human development. We could
readily prevent them, had we
the will to do so.
Barker DJP, 2011
Previous Research Focused on Adults
ALMOST
ALL
RESEARCH
Campion J et al. obesity review 2009, 10:383
The New Science Emphasizes the First 1000 days
VERY
IMPORTANT
UNDER
RESEARCHED
Campion J et al. obesity review 2009, 10:383
Diseases linked with Birth Weight
Replicated and widely accepted association with small birth size
Hypertension
Non-insulin dependent diabetes
Dislipidaemia
Impaired neurodevelopment
Elevated clotting factors
Coronary artery disease
Stroke
Described but less well replicated and accepted association with
small birth size
Chronic lung disease
Depression
Behavioral problems
Left handedness
Precocious pubarche
Schizophrenia
Fingerprint patterns
Reduced uterine and ovarian size
Described and replicated association with large birth size
Polycystic ovary disease
Breast cancer
Testicular cancer
Testicular cancer
Prostate cancer
Childhood leukaemia
De Boo HA and Harding JE, Australian and New Zealand Journal of Obstetrics and Gynaecology ,2006, 4-14
Landmark Longitudinal Cohort Study
The Framingham Heart Study
• Objective: led by NIH/NHLBI, to identify the
common factors or characteristics that
contribute to CVD
• Longitudinal Cohort Design: by following
CVD development in a large group of adults
(3 generations) over the past 60 years
• Age Groups: 30 to 62 years at enrollment
• Accomplishments: cited by the American
Heart Association among the top 10
cardiovascular research achievements of
2009.
What Framingham Study
Can’t Accomplish?
What are the root causes of chronic diseases
How to prevent chronic diseases and stop the
current epidemics at early critical time windows
(preconception, prenatal, early childhood, adolescence)
(Obesity, Diabetes, Hypertension, Dyslipidimia, Heart Disease)
Mechanisms of
Early Life Origins of Disease
Individual
Genetics
DISEASE OUTCOMES
Pre- and PostNatal
Environmental
Exposures
Epigenetics
(gene expession)
Environmental and Early Life
Experience
•
•
•
•
•
•
•
•
•
•
Nutrition
Overnutrition (too many prenatal calories)
Undernutrition (too few prenatal calories)
Malnutrition (insufficient vitamins or other essential nutrients)
Environmental Toxicants
.Chemicals originating outside the body, such as pesticides and
heavy metals
.Chemicals originating inside the body, such as hormones and
oxygen radicals
Psychosocial Stress and Behaviors
Maternal use of substances, medicines, stress
Pregnancy Complications and Birth Outcomes: preeclampsia
GDM, intrauterine growth restriction, preterm birth
Cystic fibrosis
Adult onset diabetes
AIDS
Epigenome and Health Outcomes
http://nihroadmap.nih.gov/epigenomics/pdf/epigeneticmechanisms.pdf
How to Advance the Field?
• Life Course Approach: Longitudinal
cohort studies
• Leverage Cutting-edge Science and
Technology: Integration of multi-leveldimensional data; Biomarkers
• Inter-disciplinary Collaboration: to
bridge age groups and disciplines in
order to improve health for all ages and
transform clinical and public health
practice and policy
Life Course and Gene to Society Framework
Leverage Cutting-edge Science & Technology
Genomics, Epigenomics, Proteomics, Metabolomics
Exon 1
Exon 2
Exon 3
Intron 1
Intron 2
Intron 3
5’
Exon 4
3’
DNA
rSNP
ssSNP
iSNP
cSNP
TRANSCRIPTION
pre-mRNA
SPLICING
AAAAAAAA
TRANSLATION
Mature mRNA
ORF
AUG - B1…Bn - STOP
Protein Sequence
Phenotype
protein 3D structure
Multidisciplinary Collaboration
Transdisciplinary Research
Behavioral
Patient
Neuro-developmental
Care
Epidemiology
SOM
Clinical
Medicine
SON
Early Life Origins
of Health &
Diseases
Env Health
Epidemiology
Biostatistics
Nutrition
Biochemistry MB
SPH
Bench
Research
Biotechnology
International
Collaboration
JHH
Source: Zerhouni, EA. Annual Meeting of NIH Roadmap Multidisciplinary Clinical
Research Career Development Program, 2007
Thank you!