ENABLING TRANSLATION INSTITUTE FOR CANCER/STEM CELL BIOLOGY AND MEDICINE

1. ENABLING TRANSLATION INSTITUTE FOR CANCER/STEM CELL BIOLOGY AND MEDICINE Stanford School of Medicine Leadership Retreat January 29-31, 2004

2. Background • Created in December 2002 • Purpose: • To advance fundamental research in cancer and stem cell biology • To translate discoveries to preclinical paradigms • To organize efforts throughout the University • To enhance our understanding of human diseases • To improve patient care • Past Stanford-affiliated Accomplishments: • First prospective isolation of mouse hsc (1988) • First isolation of human hsc (1991) • First isolation of mouse and human hematopoietic progenitors (2000) • First prospectively isolated brain-forming (CNS) stem cells (2000) • Fruit fly sperm-forming stem cell identified (1999)

3. Discovery => Translation => Therapy Example: Breast Cancer • Cancer-free human stem cells isolated and stored from patients with Stage IV breast cancer • Post-chemotherapy, stored hsc used to regenerate blood-forming system in patients • Blood-forming system regenerated in ≈ 2 weeks • Survival rates and cancer recurrence rates are much higher than expected from normal therapies • Future: Search for breast cancer stem cells, and define targets for diagnosis, molecular therapeutics, and immunotherapeutics by expression arrays and proteomics. • Similar experiences with non-Hodgkin’s Lymphomas

4. Discovery => Translation => Therapy Promising Animal Models (at Stanford) for studying and using hematopoietic and CNS stem cells, and new tissue stem/progenitor cells: • Spinal Cord Injury, Cerebrovascular stroke • Genetic diseases leading to brain degeneration • Transplant Rejection improvements in • Heart Transplants • Pancreatic Insulin-Producing Islet Cells • Skin Grafts • Liver • Juvenile Type 1 diabetes • Infectious diseases of CNS (Arvin) and BMT (Brown)

5. New Stem Cell Opportunities Through the Institute for Cancer/Stem Cell Biology and Medicine, we will: • Identify and recruit the best young stem cell biologists who wish to find new organ or tissue stem cells (lung, peripheral nervous system, skin, liver, pancreas, kidney, etc.) • Identify and appoint Associates and Affiliates. • Develop Affiliate ‘hotel’ space in CSCI to improve collaborations. • Establish research models to produce human pluripotent stem cells from patients with genetically determined diseases • Provide specialized research models and rigor to do it right the first time • Provide specialized instrumentation • Provide a vehicle for deeply-interested physicians, residents, graduate students, postdocs and, under the new curriculum, medical student scholars to form translational teams. • Establish educational programs for larger community.

6. Comprehensive Cancer Center Role • Discovery of cancer stem cells and the protooncogenes activated in them is a convergence of: • Classic stem cell biologists • Classical cancer gene biologists • Cancer and Leukemia oncologists • Stanford approach to cancer and cancer stem cell biology: • Recruit 1 or more of the best cancer stem cell biologists in the world • Extend the tools of cancer stem cell biology to each of the cancers commonly treated at Stanford • Recruit to Stanford 1-2 of the best cancer gene biologists • Establish Stanford as an NCI-designated Comprehensive Cancer Center and recruit and outstanding leader

7. The new Stanford Cancer Center, the Institute and NCI designation create a comprehensive approach to cancer: Stanford Hospital & Clinics & LPCH Clinical Care School of Medicine Research Institute for Cancer/Stem Cell Biology and Medicine Translational NCI-Designated Comprehensive Cancer Center Research

8. Examples of Current Translational Collaborations NEW COLLABORATIVE RESEARCH PROGRAMS TO IDENTIFY AND ISOLATE HUMAN CANCER AND LEUKEMIA STEM CELLS • Brain Cancers: Griff Harsh, Steve Huehn, Steve Skirboll,Victor Tse, Sam Cheshier • Ovarian Cancers: Nelson Teng, Amreen Hussein • Lung Cancers: Glenn Rosen • Bladder, Prostate, and Kidney Cancers: Joe Presti, Linda Shortliffe • Uterine Cancers and Endometriosis: Linda Giudice • Acute and Chronic Myelogenous Leukemias: Catriona Jamieson, Robert Lowsky, Peter Greenberg • Breast Cancers: Matt van der Rijn, Michael Clarke (Michigan), Stephanie Jeffries, Jonathan Pollock • Head and Neck (tentative): Fee, Goode, Quynh-Thu Le

9. Examples of Current Translational Collaborations COLLABORATIONS TO FIND TISSUE STEM CELLS • Pancreatic islets: Seung Kim and Roel Nusse • Cerebellum: Matt Scott • Bladder: Linda Shortliffe • Endometrium: Linda Giudice • Mesenchymal: Mike Longaker • Neural: Bill Mobley and Ann Arvin (ID) • Cardiac: Bobby Robbins • Hematopoietic progenitors: Wes Brown (ID)

10. Examples of Current Translational Collaborations COLLABORATIONS TO FIND PROGENITOR CELLS IN THE IMMUNE SYSTEM • Dendritic cells: Ed Engleman and Miriam Merad • Precursor T cells: Sam Strober • Precursor B cells: Erik Ranheim • Marrow-engrafting facilitator cells: Judy Shizuru

11. Current Translational Collaborations: Examples IMAGING AND EXPANDING BLOOD-FORMING STEM CELLS • Imaging: Chris Contag, Sam Gambhier • Expansion: Roel Nusse, Mark Kay

12. Priority hires over next several years • Cancer Center Director (in progress) • Senior appointment in pluripotent stem cell biology (as soon as space is available) • Senior Cancer Stem Cell Physician Scientist (as soon as space is available) • Cancer gene scientist in collaboration with Cancer Center Director (in 1-3 years, if space is available) • Junior stem cell biologists (in 1-4 years as space becomes available); best possible at a fundamental level, but optimally in a field that can be translated

13. Next Steps • Help raise funds for SIM 1 • Raise funds for CSCI recruitments, endowments, common core specialized instrumentation, funding for ‘hotel space’ labs in CSCI. • Recruitments as detailed. • With Steering Committee, begin process of identifying internal candidates for Associate positions in CSCI. • With Steering Committee canvas current university faculty for Affiliate positions in CSCI, and choose affiliates.