Sidney Kimmel Comprehensive Cancer Center (SKCCC) Overview

1. Sidney Kimmel Comprehensive Cancer Center (SKCCC)Overview William G. Nelson, M.D., Ph.D. Director

2. Science, Feb 16, 2001 Whole ExomeSequences of 100 Human Cancers* 11 colorectal cancers 11 breast cancers 24 pancreas cancers 22 gliomas 22 meduloblastomas 2 leukemias 1 breast cancer 1 breast cancer 4 granulosa cell tumors 1 lung cancer Sanger 1 melanoma SKCCC 3142 mutated genes 286 tumor suppressors 33 oncogenes Washington University British Columbia Cancer Research Centre Sanger Institute *Vogelstein B AACR Annual Meeting (2010)

3. Genome-Wide Epigenetic Alterations in Metastases from Men Dying of Prostate Cancer* Hypermethylation (versus normal tissues) Hypomethylation (versus normal tissues) *Yegnasubramian S, Aryee MJ et al. (2012)

4. A Molecular Description of Lethal Prostate Cancer Haffner MC, Yegnasubramanian S et al. (2012)

5. Heterogeneous Responses of Melanoma to Anti-PD-1* pretreatment biopsies from subjects (n = 30) with melanoma treated with an anti-PD-1 antibody *Brahmer JR et al. J ClinOncol28: 3167-75 (2010)

6. Translational Research in Hematology/Immunology has Revolutionized Bone Marrow Transplantation* Opportunity: Allogenic bone marrow transplantation (alloBMT) has proven benefit in the treatment of hematological malignancies and inherited bone marrow disorders. Challenge: HLA-matched bone marrow donors are under-represented among African-American and other minority populations. Solution: Innovative strategy for establishing immune tolerance in bone marrow allografts reduces graft-versus-host disease (GVHD) and making alloBMT more accessible to minority patients. *Brunstein CG et al. Blood 118: 282-288 (2011)

7. Keap1/Nrf2 Pathway for Cancer Chemoprevention* in Inducers (oltipraz, sulforaphane, others) *Ramos-Gomez M et al. Proc NatlAcadSci USA 98: 3410-5 (2001); Yu X and Kensler TW Mutation Res 591: 93-102 (2005)

8. Broccoli Sprouts Tea Intervention: HeZuo Township Qidong, P.R.C. (2003-2004)* *Kensler TW and Co-Workers

9. potentially preventable by attenuating carcinogenicity of aflatoxin B1 Age Specific Incidence Rate of Liver Cancer (Hepatocellular Cancer or HCC): Qidong and Beijing

10. Translational Development of Molecular Biomarkers at SKCCC: What are the Challenges? germline DNA variants somatic DNA mutations, translocations, etc. somatic DNA somatic methylation changes RNA expression changes, splice variants protein expression changes Biomarker Discoveries DNA Beaming, PARE, MSP, nanoMSP, MOB, COMPARE, GEMINI Regulatory/Systems Considerations CLIA, biospecimen collection/ archiving, HIPAA, health record information technology Biomarker Assay Platforms Integration into Clinical Practice

11. Improving Cancer Health at a Population Scale: Covered Lives in the Johns Hopkins Health System Cancer Prevention and Control Program members already working with these entities to establish cancer screening guidelines and improve screening performance- first project focuses on reducing over-screening for prostate cancer among elderly men

12. Individualized Health/Personalized Medicine at SKCCC and at Johns Hopkins Medicine • Individualized Health Initiative (IHI) planning led by Provost, Dean of Engineering, and SKCCC Director- launched with Scott Zeger as leader in July 2012 • Envisioned $1.5B project (>$0.5B for Epic health record/management system-investment in research information technology needed) • Brings together Schools of Medicine, Public Health, Engineering, Nursing, Arts & Sciences, Business, Applied Physics Laboratory • $30M Malone gift to Engineering • $30M Commonwealth Foundation gift to SKCCC for Personalized Cancer Medicine Johns Hopkins University Johns Hopkins Medicine Applied Physics Laboratory IHI Director’s Office Information for Health Learning Communities for Health Laboratory for Advanced Biotechnologies for Health Organizational Model for Affordable Health Develop Bioethics Framework Design New Approach for Clinical Trials Build Network Throughout Johns Hopkins Health System • Develop Better • Measurements, • Diagnostics, • and Treatments • Epigenome/ • Genome Core • High Performance • Computing Core • Statistics Core • Biorepository Apply IHI Principles, Methods, and Tools to Population Health at Significantly Lower Cost Design and Deploy New Research Information System

13. SKCCC Membership(who we are) • 254 SKCCC members from 28 Johns Hopkins Departments • 95 additions/36 departures over 6 years • Membership requires Program nomination and Executive Committee approval • Increasing diversity: 39% of new SKCCC members now non-white or female • Membership Criteria: • Principal Investigator (PI)/Project Leader of a peer-reviewed, cancer-relevant grant • Co-PI of a peer-reviewed, cancer-relevant grant • Contributor to cancer clinical protocol development • New faculty investigator with promise of meeting criteria for full membership within 3 years

14. SKCCC Programs

15. SKCCC Facilities • Current Space: 621,160 ft2 • Clinical: 323,300ft2 • Research: 222,000ft 2 • Other: 75,860 ft2 Research Program members are co-located to maximize collaboration interactions

16. SKCCC Cancer Care Delivery Sites Bayview Campus: 25,000 ft2 • New Faculty (8 positions) • Radiation Oncology ($17.1 million) • Medical Oncology ($10.5 million) • Pulmonary ($2.8 million) • Other Commitments ($6.6 million) • Clinical space- 20,000 ft2; Laboratory/support space- 5,000 ft2 Suburban Hospital: 7,000 ft2 Sibley Hospital: 30,000 ft2 All Children’s Hospital: 46,800 ft2 Johns Hopkins Singapore: 50,000 ft2

17. Trans-Disciplinary Cancer Research at SKCCC • Multiple collaborative trans-disciplinary Research • Programs • Collaborative grants rose from 18 to 30 over the past 5 including 6 SPOREs, 7 P01s, 8 U01s, 5 U54s,1 U24, 1 P30, 2 P50s • Meetings, seminars, retreats • Many points of interactions between Research Programs

18. Program Interactions Promote Team Science Hematological Malignancies Cancer Immunology Cancer Biology Viral Oncology Non-Programmatically Aligned Cancer Prevention and Control Cancer Molecular and Functional Imaging Chemical Therapeutics Brain Cancer Prostate Cancer Upper Aerodigestive Cancer 2006-2011 263 researchers 2032 collborations 643 intra-Programmatic 1389 inter-Programmatic GI Cancer Breast Cancer

19. Program Interactions Promote Team Science Hematological Malignancies Cancer Immunology Cancer Biology Viral Oncology Non-Programmatically Aligned Cancer Prevention and Control Cancer Molecular and Functional Imaging Chemical Therapeutics Brain Cancer Prostate Cancer Upper Aerodigestive Cancer 2006-2011 263 researchers 2032 collborations 643 intra-Programmatic 1389 inter-Programmatic GI Cancer Breast Cancer

20. SKCCC Grant Funding • $203.6M in cancer-relevant grants • $93.8M in NCI grants • $59.8M in other NIH grants

21. SKCCC Clinical Research Accrual Interventional studies Non-interventional studies • >2-fold increase from 2004 to 2010 • 2261 5036 • 44% extern. peer reviewed • 54% institutional Interventional accruals Emphasis on early phase (26%) and investigator-initiated (66%) intervention trials Since 2004: 61% increase in accruals to investigator-initiated solid tumor trials (401 to 665); 56% increase in overall accruals to solid tumor trials (634 to 991)

22. Training at SKCCC: A Pipeline of Talent Yearly Census of Trainees Career Choices of Hem/Onc Fellows

23. Quality of Cancer Care at SKCCC and Other NCI-Designated Cancer Centers Example: AJCC Stage I Pancreatic Cancer

24. SKCCC as a Global Asset for Cancer: Interactions/Collaborations for Key Missions Clinical Care • Diagnosis/treatment planning to ensure accuracy of tumor stage/grade guiding treatment planning • Founding member of National Cooperative Cancer Network (NCCN) • Evolving strategies for improving care quality Research • Key strengths in cancer genetics/epigenetic likely scalable • Clinical trials infrastructure/oversight expertise • Biobanking experience • Cancer prevention interventions active even in resource-poor regions Education • Strong pipeline for academically-oriented trainees • Already significant international reach of education and training experiences

25. Sidney Kimmel Comprehensive Cancer Center (SKCCC)Overview William G. Nelson, M.D., Ph.D. Director

26. Research in the Middle East The Experience at King Khaled Eye Specialist Hospital, Saudi Arabia Deepak P Edward, MD Director of Research, KKESH, Riyadh KSA Professor of Ophthalmology The Wilmer Ophthalmological Institute The Johns Hopkins University School of Medicine The Johns Hopkins Hospital

27. To contribute to ophthalmic knowledge and reduce suffering through preventions and cures of medical conditions leading to blindness and vision loss within the Kingdom of Saudi Arabia and around the world, through leadership and excellence in research, education, and patient care What is the MISSION of the KKESH – WEI Affiliation?

28. Overview of KKESH 200 bed eye hospital Operational since 1982 ~120,000 patient visits a year Joint Commission International accredited

29. Overview of Research at KKESH Personnel Clinical Research Basic Research

30. Overview of Research at KKESH Structure to Clinical Research IRB Research Council Laboratory

31. Strategic Plan Local faculty feedback Administration alignment Anonymous survey Create strategic plan NEED MANY PARTIES TO BUY INTO YOUR PLAN

32. Plan presentation • Revisions and approval • Plan budgeting • Job revisions/creation • Space allocation Research Strategic Plan

33. What is the MISSION of the KKESH – WEI Affiliation? Challenges, successes and lessons learned in establishing the research program

34. Implementation of Plan Reorganize the structure of the Department of Research

35. HIRE PERSONNEL Biostats Clinical Coordinators Basic scientists IRB Manager Epidemiologist Medical Editor LAB EQUIPMENT Small Steps Forward ROBUST IRB COLLABORATIVE AGREEMENT WITH JHU IRB SHORTEN REVIEW CYCLE FOR RESEARCH PROPOSALS

36. Enhance Visibility Enhance the visibility of KKESH as a center of research excellence in the Middle East Invite internationally renowned research Visiting Professors to assist building research programs at KKESH

37. PROMOTE VISIBILITYhttp://rd:kkesh.med.sa

38. JHU-KKESH COLLABORATION FUNDING First Cycle of funding for collaborative research between JHU faculty and KKESH faculty in process 8 studies funded Diabetes Surgical Simulation Oncology Epidemiology Genetics Second cycle 17 applications: Review process under way

39. Innovations/ Training Programs Medical student research training program Mentorship to young faculty and fellows Clinical coordinator research training program

40. Innovations/ Training Programs Other training programs How to do clinical research How to write a paper Courses planned How to make an effective oral research presentation Clinical trials/Ethics

41. Challenges/ Opportunities “IBM POLICY” HR FINANCE PURCHASING

42. International Collaborations/ Opportunities JHU collaborations Singapore collaboration Genetics Ocular Oncology

43. Identify Additional Funding Sources Leverage KACST funding to accomplish goals Ministry of Health

44. Research Strategic PlanTimelines

45. Research Strategic PlanChallenges Personnel Purchase Participation

46. Number of High impact publications with KKESH authors • Number of invited presentations globally by KKESH staff • Number of grants: by KKESH staff • Number of local trainees in research Measures of Success

47. Lessons Learned PATIENCE BUY IN AND TRUST LOCAL CULTURE POSITIVE ATTITUDE CELEBRATE SUCCESS

48. Thank you!

49. Advancing Kidney Stone ManagementA Collaborative Approach Brian R. Matlaga, M.D., M.P.H. James Buchanan Brady Urological Institute Johns Hopkins Medical Institutions Baltimore, Maryland

50. Background • Introduction of an advanced surgical technique for kidney stone management • Required education of: • Physicians • Nurses • Equipment specialists • Unique process • Tracked the effectiveness of our program