1. CTRF Leadership Meeting Institutional Partners March 3, 2003

2. © 2002 VCU 2/3/03 Minutes Corrections Approval

3. © 2002 VCU Develop Infrastructure and Intellectual Property that Enhances the Competitiveness of the Partners for Clinical and Extramural Funds Principal Objective

4. © 2002 VCU  Evaluate gene expression (and genetic changes) in human brain, ovarian, breast and hematopoetic cancers  Link gene expression (and genetic changes) to clinical findings and clinical laboratory findings (including histopathological diagnoses) in a common database  Evaluate linked data using bioinformatics Research Objective

5. © 2002 VCU Funding for CTRF

6. © 2002 VCU FY02 Funds  2nd half of the Year 2 CTRF CG Project allocation has been received. Virginia DPB asked VCU OFF BUDGETING & RESOURCE ANALYSIS on 1/21/03 to create the FATS request. VCU did so on 1/22/03 and it was approved by DPB on 1/29/03. State has approved a transfer of $500,000 to VCU for the new CTRF accounts

7. © 2002 VCU Year 1 Account Balances as of 1/29/03 (Old Accounts)

8. © 2002 VCU YR 2 Account Balances as of 2/27/03

9. © 2002 VCU Cost Sharing Report YR 1

10. © 2002 VCU Cost Sharing Report Yr 2 as of 1- 29-03 Does Not include indirect cost or In-Kind cost sharing.

11. © 2002 VCU  Cost share expenditures not paid from cost share linked accounts must be documented using ‘In Kind/3rd Party Cost Share form’ obtained from Margie Booker’s office. (http://www.vcu.edu/finance/ In-kind%20Cost%20Sharing%Certification.pdf) Cost Share Expenses

12. © 2002 VCU Cost Share Update  Meeting with all CTRF Fiscal Administrators took place on 12/12/2002 to review documents of CTRF Cost Sharing Accounts  For in deficit accounts, Fiscal Administrators to do IDTs.  Cost Sharing will be taken out of Ledger 1 Accounts and PAFs will be used to document Salaries  Cost sharing will be updated on a quarterly span

13. © 2002 VCU Reminder Cost Share Form (VCU)

14. © 2002 VCU Website Update  Website has been updated in some areas  Information is still needed regarding various focus group activities  The CTRF Website is best viewed in Internet Explorer 5.0v or better

15. © 2002 VCU  Jo Ann Breaux receiving daily notices of grant opportunities  Compiling weekly document of relevant findings  Monthly SMART documents currently on the CTRF website Training is available: http://www.InfoEd.org/default.stm SPIN Research

16. © 2002 VCU Focus Groups Tissue Bank Clinical & Pathology Laboratory Data Database Design Chip Fabrication QA/QC Data Analysis

17. © 2002 VCU Focus Group Leaders

18. © 2002 VCU VCU Tissue Bank Tissue Type Specimen Count

19. © 2002 VCU INOVA – CTRF – Tissue Bank  Jean Donovan, RN has been hired at INOVA as new study coordinator  Colleen Gilmore, RN has also been hired as part-time coordinator  Training will begin next week for both coordinators

20. © 2002 VCU Tissue Type Specimen Count INOVA Tissue Bank Brain2 Breast2  INOVA has begun accessioning tissue samples and obtaining consents.

21. © 2002 VCU  Access Database  VCU linked by LAN for several users  Computer at INOVA to be upgraded and VPN software to be installed Tissue Acquisition Database

22. © 2002 VCU Breast – Diagnosis Distribution

23. © 2002 VCU Ovary – Diagnosis Distribution

24. © 2002 VCU Hematopoietic Neoplasia – Diagnosis Distribution

25. Study ID Tissue ID Sample ID Sub-sample ID Study ID SSN Clinical Data Model Clinical Data Model (VCU) - Primary: Data Collection Secondary: Queries, Data Reduction, Anonymization Tertiary: Analysis & Hypothesis Testing AFFY TISSBK & 1 o CLINICAL & Consent CERNER PathShadw REGISTRY CLAIMS Clinical Data Repository SPOTTED Gene Expression Non-genetic predictors Treatments Outcomes MRN SSN ACCSN SEQ MRN SSN PAN MRN SSN Path Accsn Study ID Lab ID Tissue ID Run ID CEL file data Spot data Experimental (Metadata) Reg Shadw GeneX Clinical Risk Factors Treatments Outcomes Histopath Risk Factors Path Dx Clin Lab Expanded GeneX Table: Consent Info Tables: Demogrphs Risk Factrs Nutirtion Comorbidty etc Tables: Extract Info StorageInfo Usage Info etc Tables: Histopath parameters Path Dxs SNOMED Text Repts Tables: Tumor info Treatment Follow-up etc Tables: Surg Tx Medical Tx Radiatin Tx other dxs

26. © 2002 VCU GMU Informatics Update –Identified GeneX as candidate microarray database. –Worked with GeneX developers and UVA to modify GeneX to accept both cDNA and Affymetrix gene expression data –Instantiated new version of GeneX –Defined new LIMS schema for data management Create or Identify existing databases into which clinical, laboratory, tissue bank information, and expression microarray can be stored in electronic format in real time at this juncture. –Examined several available clinical databases and found none to be sufficient in terms of performance and flexibility. –Used CGO as starting basis to generate new clinical schema. –Currently implementing clinical databases. Create ODBC links between separate databases containing clinical, laboratory, and tissue bank data. –In progress. Create or Identify existing databases into which expression microarray data can be stored in electronic format in real time at this juncture.

27. © 2002 VCU CTRF CA GENOMICS TISSUE UTILIZATION - PLAN

28. © 2002 VCU Results (I)  By using T RIZOL we obtained undegraded RNA (28S/18S >1.5) but the cDNA synthesis was inhibited (accumulation of short, ~50 bp, molecules).  By cleaning up the RNA isolated using T RIZOL with the RNeasy cleanup protocol, we obtained cDNA molecules of greater size, with a max. peak at ~1,500 bp.

29. © 2002 VCU Results (II)  By using the RNeasy RNA isolation protocol from breast tissue sections, we obtained total RNA with 28S/18S ratios << 1.5, and the cDNA molecules were shorter than expected (max. peak at ~500 bp).  Therefore, we decided to isolate the RNA using TRIZOL followed by the RNeasy cleanup protocol, to ensure cDNA molecules of greater size, (max. peak at ~1,500 bp).

30. © 2002 VCU Dr. Nasim and Dr. Grant Tissue Devitalization Awaiting specimen of sufficient size to create multiple samples over time

31. © 2002 VCU Gene Expression

32. Gene Expression Data Analysis of Breast & Ovary Tumors

33. © 2002 VCU From the previous analysis we concluded that a good correlation between the histological classification and gene expression clustering could be accomplished among the cancer cases so far analyzed. Further associations between gene expression patterns and more complete histopathological and clinical data are now being analyzed intended to make gene expression profiles of tumor tissues an early predictive tool of good or bad outcome for cancer patients. Gene Expression Data Analysis of Breast & Ovary Tumors Summary

34. © 2002 VCU Dr. Guiseppi-Elie C 3 B CTRF Update February 27, 2003

35. © 2002 VCU Progress Report Completed Printing ~200 C3B10k microarrays. Hybridized Arabidopsis control oligos to 1 array from each of the four 50 slide batches to confirm viability. Begun preliminary variability studies using Stratagene RNA, and RNA from human glioma cell lines. Presented poster “Surface Chemistries and Blocking Strategies” at the annual AAAS meeting in Denver Feb 14-16. Grant proposal for $200,000 for 2 years in preparation for submission to the Brain Tumor Society. Cancer Treatment Research Fund identified for possible funding source, pregrant preparation in progress. Exchange student Derk Bemeleit from the University of Bremen in Germany has joined the C3B lab to work on gene expression in glioma cell lines.

36. © 2002 VCU  Establish Standing Weekly or Biweekly Meeting Dates and Times  Complete the Milestone Updates  Document Discussions and Progress Using Listservs CTRF – Promoting Focus Group Activity

37. © 2002 VCU  CG-TISBK: Tissue Bank  CG-CLNDT: Clinical and Pathology Data  CG-DBDSN: Database Design  CG-ANLDT: Analyze Data (Data Analysis)  CG-QAQC: QAQC  CG-LDRPI: Focus Group Leaders and PIs  CG-MEMBS: All Members  CG-FBCHP: Chip Fabrication Communication Amongst Members and Focus Groups

38. © 2002 VCU CTRF - Specific Reportables - - Reminder - -  Intellectual property reporting - licenses, patents, etc  Publications  New applications  Federal money leveraged  Private research money leveraged  Advancement of technology and economic development in VA

39. Publications & Presentations

40. Publications & Presentations Con’t

41. New Applications Identified

42. © 2002 VCU  Old Business  New Business

43. Next Leadership Meeting Will be held: Monday, April 7, 2003 at 9:30am

44. Mucinous Carcinoma (of the breast )