B. Keith English, M.D. Chair, Pediatrics & Human Development Pediatric Cross-Campus Retreat Child Health Research at MSU 11/6/15.

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B. Keith English, M.D. Chair, Pediatrics & Human Development Pediatric Cross-Campus Retreat Child Health Research at MSU 11/6/15

THANK YOU! Andre Bachmann, Ph.D. Michelle Volker Robert Schiering Debi Underwood Beth Thelen Emily Bredin Kathryn Larson

Is there a future for pediatric research? “If we do not succeed, we run the risk of failure!”

COMMUNITY CAMPUSES & CLINICAL SITES

The Future of Pediatric Research? The future of pediatric research is in team science – at the bench and in translation Focus of clinical research must switch to long-term outcomes that matter to patients and their families Will require robust informatics that will allow tracking of outcomes and provide the infrastructure for “personalized pediatrics” The OMICS revolution can help transform individual patient care – “Precision Pediatrics” - AND improve population health

Pediatric Research at MSU A “Michigan State Center for Child Health Research” -- could connect investigators across campuses, Departments and Colleges at MSU -- this research network will require robust information systems and strong partnerships with health systems -- could bring “Precision Pediatrics” to populations of children

7 Why “Precision” Medicine? Personalized, individualized, or precision medicine? For some, “personalized medicine” denotes the creation and use of unique therapies for every patient, whereas “precision medicine” refers to the “tailoring of medical treatment to the individualized characteristics of each patient” (National Research Council, 2011)

8 Why is precision medicine in pediatrics a priority?

9 Fit with Grand Initiatives and NIH Funding Priorities Fit with NICHD Funding Priorities for the next decade: –“Catalog and identify interrelated environmental and genetics factors that are key to.. health” – Focus areas include developmental origins of health and disease & behavior and cognition (interventions for autism and pharmaceutics for brain recovery) –Fit with the NIH/DARPA/NSF “Brain Initiative” –Fit with with National Human Genome Research Institute (NHGRI) funding priorities

10 Fit with MSU Multi-Campus model for pediatric research Fit with dramatic expansion of pediatric neurology, epilepsy and neuroscience in Grand Rapids in partnership with HDVCH (& with epigenetics at VARI) Fit with expanding programs in autism- related research in Pediatrics in East Lansing (connections to RAIND) Fit with public health expansion in Flint Fit with new CHM investigators in Traverse City (autism), Marquette, Midland, Southfield

11 Key Partners for “Precision Pediatrics” (1) Omics/Big Data Scientists (2) Physician-Scientists whose focus is on genomics/transcriptomics/metabolomics of major medical conditions in children (e.g., Autism/Neurodevelopmental Disabilities/Epilepsy; Childhood cancers; Asthma) (3) Health Services Researchers whose aim is to bring Precision Pediatrics to populations of children with focus on PREVENTION

Potential Impact of Precision Medicine in Pediatrics Autism: –15-20% of siblings of children with Autism Spectrum Disorder will develop autism – but 80-85% will not –If we could identify the 15-20% early on, we could target interventions designed to prevent or ameliorate autism –Genomics won’t be enough – we need comprehensive omics and biomarkers for early detection (? EEG, ? Transcriptome, Metabolome, functional imaging?) 12

Why autism needs precision medicine Heritability now estimated at 70-80% (twin studies from Sweden & King’s College London) Recent data suggest that up to 50% of cases associated with de novo “likely gene disruptive (LGD)” mutations – more likely transmitted from mother; often involving genes expressed during embryonic brain development Epigenetics also important – many environmental factors affect fetal brain development/autism risk ( parental age, maternal nutrition, maternal infections/inflammation, toxins, stress) 13

Precision Interventions for children with autism? Great frustration in the field – despite major advances in understanding of role of many genetic and environmental factors, this has not translated into specific interventions Proof of concept greatly needed – targeted intervention in specific subset of children with or at risk for autism Rapamycin trial for children with tuberous sclerosis and autism underway.. 14

Downstream of TSC genes 15

Another Potential Impact of Precision Medicine in Pediatrics Congenital CMV infection –Affects 1/150 to 1/200 neonates in the U.S. –Most asymptomatic at birth, but 10-15% of the asymptomatically infected neonates will develop significant hearing loss – yet 80-85% will not –If we could identify the 10-15% who will develop hearing loss early in life, we could target preventive strategies and intensify followup (genomic, epigenomic, metabolomic markers?) 16