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US Opportunities at the Intersection of Physical and Life Sciences Jonathan Franca‐Koh Program Manager Physical Sciences‐Oncology Centers (PS‐OC) Program, Office of Physical Sciences Oncology (OPSO), Office of Physical Sciences – Oncology (OPSO) CSSI, OD, NCI, NIH In the U.S., Cancer Continues to Represent an Enormous Burden • 569,490 Americans died of cancer in 2010 • 1 529 560 Americans 1,529,560 A i will ill be b diagnosed di d with ith cancer this thi year • $124.6 billion in 2010 for cancer healthcare costs Unlike Other Major Disease Killers, Cancer Continues to Take Nearly the Same Toll as it did in 1950 Death h Rates Per 100,00 00 Americans s 600 586.8 1950 2008 500 400 300 203 1 203.1 200 100 193.9 186.2 180.7 44 48.1 18.5 0 Heart Diseases Cerebrovascular Diseases Pneumonia/ Influenza Cancer Source for 2010 deaths and diagnoses: American Cancer Society (ACS) 2010 Cancer Facts & Figures; Atlanta, Georgia Source for 2008 age-adjusted death rate: National Center for Health Statistics, NCHS Public-use file for 2008 deaths. Global Burden: By 2020, Cancer Mortality 10 M/yr (Incidence 16 M/yr) Source: IACR, WHO Limited Progress in Reducing Cancer Death Rate (Per ( 100,0 000 Age A Adjusted) Mortality M y 600 500 Heart 400 300 Cancer 200 100 1970 1975 War on Cancer 1980 1985 1990 1995 2000 2005 4 Merging Physical & Life Sciences “New Biology” – 2009 “Intersection of the Physical & Life Sciences – 2010 A “Conference on Research at the Interface of the Life and Physical Sciences: Bridging the Sciences” was conducted on November 9, 2004, in Bethesda, MD. The meeting, sponsored by NIH/NIBIB and NSF, to obtain community input on how to bridge the life and physical sciences. “Bringing Bringing physics physics, not just the physicists, physicists to biology” – Harold Varmus, NIH Director Centennial Speech, APS March Meeting, 1999 Susan Hockfield, MIT President, Science, 2009 “In biomedicine,…we can harness the historic convergence between life sciences and physical sciences that's underway today; undertaking public projects -- in the spirit of the Human Genome Project -- to create data and capabilities that fuel discoveries in tens of thousands of laboratories; and identifying and overcoming scientific and bureaucratic barriers to rapidly translating scientific breakthroughs into diagnostics and therapeutics that serve patients…” – President Obama, NAS Speech, April 2009 Including Unique ‘Perspectives’ Shigeo Fukuda Including Unique ‘Perspectives’ that Add Insight Shigeo Fukuda Merging “Perspectives” – the whole is more than the sum of its parts Physical Scientist Cancer Biologist How much energy is needed to do this? How much force does it take to cross this barrier? Are reactions rates altered during this process? How much time does it take? What are the spatial effects? ff ? What cell, molecule, tissue is it? What changed? Where does this fit? Do I see the same thing in several tumors? Different ‘views’ of the same picture Having H i b both h perspectives i yields i ld a more comprehensive h i (clearer) picture of what cancer is and how it functions at all levels – especially at the sub-molecular/atomic scales Bringing In New Perspectives: Brainstorming with Experts Consensus Scientific Themes Understanding the Physics of Cancer Evolution and Evolutionary Theory in Cancer Coding, Decoding and Transfer of Information in Cancer “De-convoluting” the Complexity of Cancer Consensus Needs Establish trans-disciplinary physical sciences-oncology centers Centers composed of integrated physical sciences-oncology teams Focus on theme(s) for center framework ~300 extramural participants Centers led by physical scientists with cosenior investigator(s) from cancer biology/oncology PS-OC Network: Physical scientists & cancer biologists/oncologists integrated from the start g g g Liphardt Weaver UC Berkeley Hillis O’Halloran Licht Northwestern Shuler Hempstead van Oudenaarden Jacks MIT Cornell Agus Michor Holland USC DFCI PS--OC Network PS Scripps Kuhn Davies Austin Bethel ASU Grady y Princeton TMHRI Ferrari Curley y Moffitt Gatenby y Gillies Tlsty Johns Hopkins Wirtz Semenza PS-OC Network: 50+ Institutions in the U.S. and Beyond Eran Segal, Weizmann Institute – Investigator Northwestern PS-OC Alexander Van Oudenarden and Hans Clever, Hubrect Institute – Investigators MIT PS-OC Timothy Newman and Alastair Thompson, University of Dundee – Investigators ASU PS-OC Philip Maini, University of Oxford – Investigator Moffitt PS-OC PS-OC Operation: Interactions Inside and Outside of Network PS-OC Network External Research Communities PS-OC Organizing Framework Project 1 Project 2 Project 3 Project 4 Core B Core A Education and Training Unit Pilot Projects Trans-Network Admin Unit Core B Core A Project P j t 1 Project P j t 2 Project P j t 3 Project P j t 4 Trans-Network Admin Unit Pilot Projects Organizing Framework PS-OC Outreach Projects TransNetwork Projects Trainee Exchange Education and Training Unit Outreach and Dissem Unit Outreach and Dissem Unit Outreach Projects Tumor, Cancer, and Metastasis ““…>90% >90% of deaths is caused ca sed b by disseminated disease or metastasis…” Serous ovariaan Lungg squamo ous GBM Cancer: A Disease of the Genes! GBM: 400 cases, Lung squamous: 113 cases, Serous ovarian : 486 cases Cancer: A Disease of Pathways! Cancer: A Disease of Biomarkers and Microenvironment! Phosphoprotein Expression and Postsurgical Ischemia: Case A pMAPK Immunostaining (Ventana) Case B 10 min Change of pMAPK expression after 10-20 min cold ischemia 20 min 60 min Slide Compliments of Dr. Hartmut Juhl, Indivumed GmbH, Hamburg Perspective: Critical to Think in Terms of Space and Time Theme: Physical Laws and Principles – New Conceptual Approaches Force Force Force Force Biology is not exempt from physical laws and principles Forces (shear, compressive, pressure, etc.) are experienced by metastatic cells Quantify, catalog, and determine impact and outcomes of forces Force Primary tumor “leak” leak cancer cells into vasculature and establish secondary sites Well-known to be an inefficient process (0.01%) ~1 million cells per day! Cell Mechanics: An Emerging Field With Potential Intersection with Cancer Manuscripts Citations Statistics generated using Web of Science with keywords “cell mechanics” and “cancer” PS-OC Network Research: Cell Mechanics Velocity MDA-MB-231 - single MDA-MB-231 - confluent MDA-MB-231 in MCF10A JHU & ASU PS-OCs– Biophysical Journal, Volume 102, Issue 12, 2731-2741, 20 June 2012 UC Berkeley PS-OC – Proc Natl Acad Sci U S A v.109(6); Feb 7, 2012 PS-OC Network Research: CTC Technology Scripps PS-OC – Editorial & 5 articles in Physical Biology, Vol 9, February 2012 All 103 circulating tumor • Fluid Biopsy in Patients with Metastatic Prostate, Pancreatic and Breast Cancers, cells identified on 1 slide • Characterization of circulating tumor cell aggregates identified in patients with epithelialfrom tumors a Stage IV prostate cancer patient. • Cytometric comparisons between circulating tumor cells from prostate cancer patients and the prostate tumor derived LNCaP cell line Scripps: 1129 CTC/7.5ml • High definition imaging of circulating tumor cells and associated cellular events in non-small cell lung Veridex: 1 CTC/7.5ml cancer patients; a longitudinal analysis • Fluid biopsy for Circulating Tumor Cell identification in Patients with early and late stage Non-Small Cell Lung Cancer; a glimpse into lung cancer biology Cornell PS-OC – PLoS One. 2012;7(4):e35976. Epub 2012 Apr 27. PS-OC Network Research: DNA Mechanics Northwestern PS-OC – Nature. 2012 Jun 3. doi: 10.1038/nature11142. DFCI PS-OC – Nature Biotechnology 29, 1103–1108 (2011) MIT PS-OC – Nature Biotechnology 29, 1109–1113 (2011) Biomaterials in Cancer Research Tools to develop a deeper understanding of cancer cell adhesion, migration, and extracellular matrix remodeling Tepuis – Princeton PSOC Fraley SI et al. Nature Comm. 2012 Liu L et al. PNAS 2011 3D Hydrogels – JHU PSOC OPSO Website Contains Relevant Active Funding Opportunities http://www.OPSO.cancer.gov/funding/opportunities.asp PS-OC Funding Opportunity: PS-OC Pilot and Outreach Pilot Project j Opportunities pp • Cornell University PS-OC (Outreach Pilot projects) http://www.psoc.cornell.edu/outreach-pilot-projects-outreach-pilot-projects.html • Johns Hopkins University PS-OC (Pilot projects with a JHU collaborator) http://psoc.inbt.jhu.edu/research/funding/ • Northwestern University PS-OC (new Pilot and Outreach Pilot opportunities expected Spring 2013) http://www.psoc.northwestern.edu/funding-opportunities/pilot-projects // /f / http://www.psoc.northwestern.edu/funding-opportunities/outreach-pilot-projects • Princeton University PS-OC (Pilot Projects with evolution focus) http://www.princeton.edu/psoc/pilot-projects/ PS-OC Funding Opportunity: NCI/NSF Collaboration Physics and LIfe Sciences Early Research (PLIER) Awards R l Release D t : Closed Date Cl dF Feb. b 15 NSF Award Amount: $125 K for 3 years E Expected t d # Awards: A d 5–6 Public Program Announcement Relevant Active NIH Funding Opportunities • Transforming g Biomedicine at the Interface of the Life and Physical y Sciences ((R01)) • • Nanoscience and Nanotechnology in Biology and Medicine ( R01, R21) • • PA-11-148 PA 11 148 , PA PA-11-149 11 149 [Issued by NIBIB] Development of Multifunctional Drug and Gene Delivery Systems (R01) • • PAR-10-141 [NIGMS/NIAMS/NIBIB] PAR-10-048 [Issued by NIBIB] Early Stage Innovative Technology Developments in for Cancer Research (R21) • RFA-CA-12-002 [NCI] Use RePORTER (http://projectreporter.nih.gov/reporter.cfm) to find collaborators, evaluate the status of research fields, find receptive ICs and study sections Learn More about PS-OCs: (physics cancer gov) (physics.cancer.gov) More Information Jonathan Franca-Koh, Ph.D. Program Manager, PS-OC Email: f [email protected] k hj @ il ih Larry Nagahara, Ph. D. Director,, OPSO Email: [email protected]