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Research Symposium October 21, 2016 Collaborations • School of Public Health and School of Medicine • Focused on the AHS2 Sidewalk conversation… Should do something to capitalize… Vision 2020 Torrey Pines Conference… Idea… • Use newly available molecular techniques to figure out the “black box” between the inputs and outputs already observed by the AHS2 • Take advantage of our high concentration of healthy elderly to identify what molecular pathways (genes, epigenomic patterning, proteins, metabolites) are “ideal” and lead to slower aging • Use these findings to see what kinds of interventions work and don’t work Adventist Health Study Epidemiologic Data AHS Molecular Description of Health • Genome • Epigenome • Transcriptome • Small RNAs • Proteome • Telomere length • Metabolome Outcomes Data Indicators of Biological Aging » Epigenetic patterning ~ Small, methyl molecules can get added to specific cytosine residues ~ Turn off the downstream gene ~ As we age, our pattern of what genes are and are not turned off changes ~ So, looking at our epigenetic pattern gives an estimate of biological age » Telomere length ~ Telomeres are the “caps” at the ends of our chromosomes ~ They get shorter with each cell division, and with time ~ Therefore, telomere length can also give an estimate of biological age Refinement and development • Lots and lots of input! • Pilot data – established that we had something • Four threads – Center for Genomics – Collaborative project and team – Telomeres – Health Disparities Pilot Data • GRASP 2012 – Valery Filippov and Karen Jaceldo – Impact of diet on proteomics, epigenomics and pathway activation – Generated important pilot data – we were, indeed, onto something! • Diet can, indeed, change the epigenetic patterning • The AHS2 cohort seems to age more slowly than the “normal” • Psychosocial influences can change telomere length and rate of aging Thread 1 – Center for Genomics • Great idea…but how and who can make it happen? Appropriate expertise and equipment was missing on our campus. • Learned that Charles Wang might be available... • Recruited Charles (Thanks, Dr. Hadley!), who came to LLU and set up a Center for Genomics Thread 1, Continued • Equipment – Mid-sized sequencer (NexGen) – NIH grant to Dr. Wang – Large sequencer (HiSeq 4000) – Funds from the Ardmore Foundation and the Sims Foundation – Other equipment – SM • Other grant applications – at least one is in review Thread 2 – Collaborative Project and Team • Internal Funding (Thanks!) • Team – Penelope Duerksen-Hughes, Valery Filippov, Charles Wang, Xin Chen, Jan Lloren, Gary Fraser, Michael Orlich Thread 2 - Continued • Making group decisions about the direction of the research – Increased the number of specimens analyzed in order to strengthen or disprove the preliminary data – Problem solving – Developing additional collaborations – Strategizing for next steps Thread 2 - Continued • 3 manuscripts in preparation – Cohort effect – Effect of diet on pathway activation – Diabetes, “normal” and AHS2 comparison • Mutual support – AHS2 Infrastructure grant (under review) Thread 3 - Telomeres • Initial work with Ray and Synnove Knutsen • My lab measured telomere lengths for individuals who were part of both AHS1 and AHS2 • The Knutsens then matched our telomere length results with responses to questions asked in the 1970s Thread 3 - Continued • Mothering style and father’s presence affected telomere lengths – 30 years later! • GRASP 2014 – P Duerksen-Hughes and Raymond Knutsen – Will increase the number of specimens analyzed, plus be able to dig deeper into the psychosocial history of individuals and in particular, into Adverse Childhood Events Thread 4 – Health Disparities • I have been a member of the CHDMM since I came to Loma Linda, so I think about Health Disparities quite a bit. • Saw the following announcement: Thread 4 – Continued • Now working on an application (due November 15) – Two Co-PIs What we have now that we didn’t have before… • Existing (internal) funding – GRASP 2012, GRASP 2014 and other internal $$ • Potential (external) funding – – – – AHS2 infrastructure grant Wang’s NIH R01 application(s) Health Disparities focused grant Others • Center, cutting-edge equipment and a Director with genetics/genomics expertise What we have now that we didn’t have before… • Papers in the pipeline • New insights • Sense of urgency to get the papers out!