The Hormel Institute University of Minnesota, Hormel Foundation, and Mayo Clinic

1. Finding the cure for cancer in the foods you eat everyday The Hormel InstituteUniversity of Minnesota, Hormel Foundation, and Mayo Clinic

2. Grand Opening October 3, 2008

3. The Hormel Institute 60th Anniversary ofThe Hormel Institute2002–65 years in 2007 • Legacy of Jay C. Hormel whose dream was to create a scientific research laboratory in his hometown of Austin. • Established 1942 in an agreement with The Hormel Foundation and University of Minnesota • Mission of The Hormel Institute is to conduct research in the biological sciences with applications in medicine and agriculture. Mr. Richard Knowlton

4. Originally, the R&D of Hormel Foods and The Hormel Institute were one and the same OS Privett H Mason Developing the miniature pig Working on food preservation & lipids G Mizuno ArlenePrivett JA Ulrich

5. Current Research Sections Translational Cancer Research: D.J.Liao Signal Transduction & Apoptosis: P.Ruvolo Cancer Biology: J. Lu Membrane Biochemistry: R.E.Brown Nutrition & Metabolism: M.P.Cleary Biophysics: H.L.Brockman Stem Cells & Cancer R.J. Morris Molecular & Cellular Biology Cellular Dynamics: E. Hinchcliffe Cell Death and Cancer Genetics: Y. Deng A.M.Bode Z.Dong

6. Blue Gene/L Supercomputer The first phase of development was the purchase (01-01-08) of the world’s fastest supercomputer, the Blue Gene/L –currently housed at The Hormel Institute.

7. X-ray Crystallography The second phase of development was the completion (05-01-09) of our own protein crystallography laboratory, including robotics and diffraction system.

8. These technologies are an engine that supports a wide variety of applications to drive BioBusinessand BioScience in Minnesota and around the world.

9. CANCER Heart Disease Cancer has surpassed heart disease as the number 1 killer of Americans under the age of 80

10. initiation promotion Cancer occurs in stages: progression Each stage is a potential target for anticancer or prevention agents, especially promotion

11. To win the war against cancer: We must know the enemy–we must understand how cancer develops. The prevailing thought today is that cancer may be prevented or treated by targeting specific genes and proteins found only in cancer cells.

12. Smoking is the major risk factor for developing cancer Diet is the second major risk factor for developing cancer

13. The Hormel Institute proteins and genes

15. The human body is made up of billions of biological molecules that form intricate cellular pathways designed to work together to promote optimal health. Understanding the integration of these pathways and how disturbances in their function might lead to diseases, like cancer, is critical to determine how disease can be prevented or cured.

16. Key players in these pathways are tiny molecules known as proteins, which are manufactured from genes containing DNA.Proteins are the miniature machines that allow us to live healthy, productive lives. Each protein has a unique 3-D shape that is critical for normal function and if that shape is damaged, diseases such as cancer occur.

17. Furthermore, small molecules, natural or synthetic, are important for researchers to investigate proteins in biological pathways and are extremely valuable for treating disease. A fundamental challenge is the ability to successfully identify small molecules that are effective at modulating a particular biological process or disease state.

18. The Hormel Institute ICRT is providing the technology needed to accelerate this process of discovery. The net result will be a greater understanding of biological systems for improving the quality of life in Minnesota, the nation, and the world and a dramatic, positive impact on economic development in Bioscience and Biotechnology for the state of Minnesota.

19. supercomputer screening experimental verification The Hormel Institute

20. Computer Modeling and Biological Simulation An extremely powerful technology that is beginning to be used extensively to predict interactions between 1) cellular proteins 2) small molecular inhibitors (i.e., anticancer compounds) and cellular proteins

21. A collaboration that includes The Hormel Institute (U of M), the Mayo Clinic Rochester, and IBM: To establish the first Interdisciplinary, All-University Graduate Program in Biomedical Informatics and Computational Biology. The Hormel Institute and IBM are currently funded by BICB for a collaborative project to use a Blue Gene/L supercomputer to develop specific small molecule inhibitors of ERKs. 

22. The Hormel Institute for prevention of disease – maintaining good health – excellent quality of life

23. Many natural dietary components or other natural compounds exert anti-cancer, anti-inflammatory, and anti-aging effects

24. Virtual Screening Process • Experiment ZINC Database UCSF • Filters: Grid scoring function Amber scoring function • 2 – 3 Million molecules • In vitro • In silico

25. 6-gingerol effectively prevents UVA-induced skin cancer and colon cancer • Using supercomputer technology, we have now discovered the protein target of 6-gingerol. • Over the last year, Mayo Clinic Pharmacy has provided various test formulations with 6-gingerol for preclinical studies now in progress • Mayo Clinic Pharmacy will prepare formulations for phase I and II clinical trials • Mayo will conduct the phase I and II trials Work funded by Pediatric Pharmaceuticals

26. Difluoromethylornithine (DFMO) Pre-DFMO Post-DFMO • Ornithine analog • Irreversible inhibitor of ODC enzymatic activity • DFMO is toxic–associated with hearing loss • We have discovered a natural compound inhibitor that appears to be just as effective without the toxicity

27. Mayo Clinic Patients Office of Translational Research The Hormel Institute basic research results clinical results

28. in The Hormel Institute University of Minnesota Mayo Clinic Finding the cure for cancer in the foods youeat everyday– The Hormel Institute Striving to be the very best!

29. Connecting the Best of Private and Public Sectors to Advance Research and Technology

30. Rochester Higher Education Development Committee (RHEDC) “Establish a world-class higher education institution that leverages the U of M research capability, in partnership with IBM, Mayo Clinic, and other industry leaders, to build signature academic and research programs that complement SE Minnesota’s leadership roles in health sciences, biosciences, engineering, and technology. Educational programs will provide applications to economic activities via innovation, translational research, and clinical experiences.”

31. UM Partnership Programs Biomedical Informatics and Computational Biology Bachelor of Science in Health Sciences 30 Academic Programs New Programs MS Biostatistics u Principal’s Academy Center for Learning Innovation Unique curriculum structure u Innovative learning platform All-University Graduate Program In collaboration with Hormel Institute, IBM, Mayo Clinic, U of M Twin Cities Programmatic Structure

32. Building Partnerships - BICBBiomedical Informatics and Computational Biology

33. UMTC BioInf/Comp Bio Resources Collaborations UMR BICB Resources Collaborations U of M Rochester Interface Mayo Clinic BioInf/Comp Bio Resources Collaborations IBM BioInf/Comp Bio Resources Collaborations Other regional BioInf/Comp Bio Resources Collaborations

34. Making the Connections • Speed Dating • Symposia

35. Research Seed Grants • Five 2 year $100K grants awarded (Fall 2007) • Collaboration with Mayo Clinic, IBM, Hormel Institute • Four 2 year $100K grants awarded (Fall 2008) • Collaboration with Mayo Clinic, IBM, Hormel Institute • Research Symposia • + 80 attendees January 2008 • + 90 attendees June 2008 • +130 attendees January 2009 • +140 attendees in June 2009 • Major focus of grants • Data mining methods for clinical and laboratory data • Computational methods for rational drug design • Machine learning

36. Launching the Academic Program • BICB MS/PhD degree program began Fall 2008 • Program proposal developed by faculty and staff from UM, IBM, Mayo Clinic, and Hormel Institute • Regents approval in July 2008 • Nine students based in Rochester(2 PhD and 7 MS) • Nine students based in Twin Cities(8 PhD and 1 MS) • Traineeship program started Fall 2007 • Fifteen 2-year traineeships awarded • Co-advisors from UM, IBM, Mayo • Leverage existing UM graduate programs and students • Students can take Mayo and UM courses

37. Milestones • 25 Research Reports Published since 2008 • IBM SUR grant • IBM Computing Resources • Partnership with MSI • UMCB Laboratory focused on BICB research • BICB Research Bulletins • BICB investigators receive $1.1 million NIH grant • 466% increase in symposia attendance from March 2007 to June 2009 • Joint Study Agreement with IBM

38. Sustaining Growth • Host two symposia each year • Foster joint proposal submission • Seek program specific funding • NSF IGERT grant • Instrumentation grants • Student recruitment • Joint advertising w/Health Informatics • Build and nurture organizational relationships • IBM, Mayo Clinic, U of M Joint Study Agreement • Leverage MSI and UM OIT

39. What We Have Learned Develop Institute for Advancement of Research Partnerships • Build on the Minnesota Partnership with Mayo Clinic Rochester • Identify and build research collaboration driven by both U of M and Mayo Clinic Rochester • Provide the administrative umbrella to assemble research teams that are cross-disciplinary, cross-institutional, cross-sector, multi-state, and multi-national.