NCRR: Navigating the Translational Researcher Primate Models and Resources

1. NCRR: Navigating the Translational ResearcherPrimate Models and Resources Stuart Zola, PhD Professor, Department of Psychiatry and Behavioral Sciences, Director, Yerkes National Primate Research Center, Co-Director, Alzheimer’s Disease Research Center, Co-Director, Center for Behavioral Neuroscience Emory University, Senior Research Career Scientist, VA Medical Center, Atlanta Member, International Brotherhood of Magicians

2. Resources

3. Eight National Primate Research Centers National Institutes of Health, and National Center for Research Resources (NCRR) ~ 26,000 Nonhuman primates

4. A Unique Research Environment of Collaborative Research Groups • Imaging Center (fMRI, PET) • Microarray Facility - Affymetrix Rhesus • gene chip • - Chimpanzee colony • - Rhesus colony and six other species • - Aging populations in all species • - Enrichment and psychological • well-being programs • - Behavioral assessments that • reach across all species • - Center for Aids Research • - Vaccine Research Center • - Center for Behavioral Neuroscience • - Living Links Center Yerkes National Primate Research Center Emory University 26 States NIH Georgia Tech Georgia State

5. NIH/NCRR Biomedical Informatics Research Network (BIRN) Emory Univ. Yerkes NPRC Mediator architecture Knowledge-based mediation Integrated view definitions

6. Biomedical Informatics Research Network (BIRN) What is data mediation? The Biomedical Informatics Research Network (BIRN) will use a “mediator architecture” to link multiple databases with different schemas, maintained at different research institutions into a data federation. This type of architecture is flexible, scalable, and powerful. It allows individual researchers to manage their own data in databases tailored to meet their specific needs. Those searching the system, however, will see the BIRN Data Federation as if it were a single database. Queries will be issued against the “mediator”, a virtual database that combines the individual data sources in meaningful ways. This combination is achieved using “Integrated View Definitions” which describe how the mediator represents the source databases. A user will submit a query to the mediator (or more precisely, to one of the integrated views the mediator can expose). The mediator will then parse the query and submit one or more queries to the relevant data sources.

7. NCRR Nonhuman Primate Resources National Primate Research Centers Criteria and Procedures for Accessing National Primate Research Centers California National Primate Research Center New England National Primate Research Center Oregon National Primate Research Center Southwest National Primate Research Center Tulane National Primate Research Center Washington National Primate Research Center Wisconsin National Primate Research Center Yerkes National Primate Research Center Baboon and Monkey Research Resources Baboon Research Resources Caribbean Primate Research Center Program Squirrel Monkey Breeding and Research Resource Chimpanzee Biomedical Research Resources Alamogordo Primate Facility Applied Research for Improving Behavioral Management of Captive Chimpanzees Primate Foundation of Arizona University of Louisiana at Lafayette University of Texas Yerkes National Primate Research Center Specific-Pathogen-Free Macaque Resources Herpes B-Virus Diagnosis: National Resource Laboratory New England National Primate Research Center Specific-Pathogen-Free Rhesus Macaques Specific-Pathogen-Free Rhesus Monkey Genetic Analysis Resources Genetic Analysis of Complex Traits Genetics Typing Laboratory Referral Center for Animal Models of Human Genetic Disease

8. Integrated Primate Biomaterials and Information Resource Coriell Institute for Medical Research (www.ipbir.org) Purpose: to assemble, characterize, and distribute high-quality DNA samples of known provenance with accompanying demographic, geographic, and behavioral information in order to stimulate and facilitate research in primate genetic diversity and evolution, comparative genomics, and population genetics. NIA Primate Aging Database (http://pad.primate.wisc.edu) Purpose: to collect data on normal aging in a wide range of NHP species. Blood chemistry, body weight across the lifespan. Currently 400,000 data points from 16 different species. NCRR Rhesus monkey genetic tools workshop, April 19-20

9. Primate Models

10. Nonhuman primates provide research models for conditions that affect us throughout our life-span. • Autism • Visual System Development • Cognitive Development • Social//Emotional Development • Genetics, Proteomics • Immune System Function • Cancer • AIDS • Malaria • Cocaine Addiction • Cardiovascular Disease • Transplantation Medicine • Alzheimer’s Disease • Parkinson’s Disease • Neurological Basis of Behavior • Cognitive and Social Changes • in Aging

11. Changes in Cognition And Neuropathology Across Time and the Diagnosis of Mild Cognitive Impairment (MCI) Cognitive Ability Primarily Memory Additional Brain Regions Dementia, including AD Normal MCI Primarily Hippocampus Other Cognitive Abilities Neuropathology

12. Recognition Memory: Assessed in identical ways in humans and monkeys

13. Recognition Memory Humans Monkeys

14. Noninvasive Infrared Eye-Tracking: Familiarization The Preferential Looking Task

15. Noninvasive Infrared Eye-Tracking: Test Control Subjects

16. Noninvasive Infrared Eye-Tracking: Test MCI patients and monkeys with hippocampal damage

17. No significant differences MCI vs PD, CON P<.01, .001 MCI fall to chance within a 2-min delay No evidence of deficits in attention, motivation, or perception in MCI

18. PD vs CON P<.05 2 sec PD vs MCI P<.01, .05 MCI patients fixate for shorter time than the PD patients PD patients fixate longer than CON and MCI

24. PET Imaging in Rhesus Monkeys • DAT Occupancy • anesthetized monkeys • [18F] FECNT • Brain Activation • awake monkeys • [15O] water

25. Rhesus 30 directions EPI 1.3x1.3x1.3 microns

26. Dec 14, 05 (Wed) Chimp Jeanie Acute Stroke Flow void of MCA Pathway of Motor tract Motor-Foot Motor-Hand Motor-Face Motor-Swallow Sylvian Fissure Temporal Lobe Flow void of ICA T2-WI ADC map Flash T2* & DWI trace

27. Yerkes NPRC Chimpanzee Projects Include:Cognition and AgingHepatitis CMalariaAIDS

28. Yerkes NPRC Social Cognition: Joystick Studies Face recognition Inversion effect Kin recognition Categorize facial expressions -> Affect recognition using multimodal cues

29. Transgenic Monkeys • Born with mutant gene, e.g., over-expression of protein • Short time to expression • Treatment interventions • Behavioral assessments

30. Biomarkers and Brain Imaging Amyloid plaques PET scan

31. Vaccines for Noninfectious Diseases • Elan vaccine, AN-1792 • Designed to attack and clear out plaques. • Mice immunized at a young age were protected from plaque deposits; in animals that already had deposits, they were halted and in some cases reversed. • Clinical trials stopped; inflammation of brain. • Deposits of amyloid in blood vessel walls in old monkeys.

32. Sequencing of Human and Nonhuman Primate Genomes (Chimpanzee, Rhesus monkey…) • Yerkes Chimpanzee, Clint • Differences in genome important; Similarities in genome important. • Where and when are genes important for memory function expressed? • How are cells expressing these genes influenced by the environment? New finding of structural variation in normal subjects. Individual differences? • Where do we spot points of vulnerability that can make the difference between healthy memory and diseases that impair memory?

33. Nonhuman Primate Models Genomics Behavior Imaging Infrared Eye-tracking MRI Microarray Experiential Impact Analysis PET Gene Expression 3-Dimensional Video Tracking Optical Transgenics Bioinformatics Translates Data into Knowledge Basic and Translational Research Therapies Diagnosis Interventions

36. Declarative Memory System

38. Yerkes NPRC Chimpanzee Cognitive Testing Facility

39. Familiarization Delay Delay Test Familiar Novel