Recent Advances in Occupational and Environmental Health Research Howard Hu MD MPH ScD

Career on a slide… Boston City Hospital: Internal Medicine, : Full Professor with Tenure Parents immigrate from Shanghai & Beijing 1946 Born in New York City Brown University Albert Einstein Medical School Shipyards & Public Health Summers of ’73,’74: shipyards Department Chair, U Michigan… Dean July 2012

Our heritage The Dalla Lana School of Public Health

2008: Recreated 2013: Became Full Faculty 2014: Merged with Institute for Health Policy, Management & Evaluation 2014: Created Waakabinesse-Bryce Institute for Health with $10M Dan Family gift 2015: Merging with Joint Centre for Bioethics

Outline The micro: understanding the “true” footprint of occupational & environmental risk factors on health  Advances in molecular epidemiology, exposure science, “big data” The macro:  Built environment, mega-cities, big data  Climate change, planetary health

Genes v. Environment? Studies of twins Concordance of disease occurrence in monozygotic (MZ) v dizygotic (DZ) twins  high in MZ/ low in DZ high heritability (genes!)  medium in MZ/ medium in DZ low heritability; high influence by environmental factors shared by twins  low in MZ/ low in DZ low heritability; high influence by environmental factors specific to each twin

The unexpectedly large influence of et al., (NEJM, 2000) environment on cancers: the Scandinavian Twin Study Genetics only explains 27% of breast cancer “Shared” environment only 6% Individual environment explains 67%

Similarly, we can examine concordance in other CDs Parkinson’s: ~20-30% Alzheimer’s (Late onset, >65 yo): ~40% Essential Hypertension: <40% Osteoporosis: <40% Schizophrenia: <40% Gene-environment interactions ??

The 3 most difficult challenges to environmental epi research Exposure  i.e., measuring, estimating, modeling exposures to chemical toxicants, the relevant timing, and the dose- response relationship  What metric of exposure is biologically most important? Current? Cumulative? Peak? At some specific lifestage? (Timing)  What is the dose-response? Monotonic linear? Threshold? U-shaped?

25 years of research on a global pollutant: lead Paint, pipes, leaded- gasoline, food cans, many other products…

The hidden problem: The impact of cumulative lead exposure (bone lead levels) Hu et al, 1996

BONE LEAD AND HYPERTENSION In community-exposed men.* *Adjusted for age, body mass index, family history of hypertension, smoking, alcohol ingestion, dietary calcium, dietary sodium Hu et al, 1996

BONE LEAD AND MORTALITY In community-exposed men* Weisskopf et al, 2009 *Adjusted for age, body mass index, smoking, race

*Adjusting for age, smoking BONE LEAD AND CATARACTS In community-exposed men* Schaumberg et al, 2004

Lead, the Hemochromatosis genes C282Y/H63D, and Cognition More intracellular iron and lead  Synergistic promotion of oxidation HFE carrier adults had worse cognition given same lead burden Wildtype HFE carriers Wang et al, 2006

Fetal exposure to mom’s mobilized bone lead stores independently predict poorer offspring IQ at age 2 years

Knowledge Translation New recommendations for adults explosed to lead New recommendations for lead and pregnancy

New Direction: Is early life lead exposure a risk factor for Alzheimer’s ???

Post-mortem brains  Alzheimer’s v Control Epigenome discovery Transmembrane Protein 59 identified  responsible for post- translational glycosylation of APP  leads to retention of APP in the Golgi apparatus Studies on lead exposure in progress Bakulski et al, in press

EXPOSOMICS -Proposes to use available measures of external human exposures -…combined with advanced, high through-put methods -…to develop a comprehensive profile of human exposures over the life course. Wild C, 2012 Example

Near term strategy: chop up the lifecourse into discrete, simultaneously observed segments

The macro Built environment, mega-cities, big data Climate change, planetary health

- Population-based cohort study of >230,000 Ontarians aged 18+ years - Questionnaires, Biospecimens Physical measurements, Clinical data - Data linkage to administrative health data (from universal health coverage system x 20+ years) -The Institute for Clinical Evaluative Sciences

Map of Ultrafine Particles in Toronto Evans lab: Sabaliauskas et al. Atm Env

Merging of health, environment, social data Policy-relevant research using “Big Data” resources

Climate change: Spectacular inequities

The ultimate experiment…

Thanks! (This ppt available on request from