US Opportunities at the Intersection of Physical and Life Sciences

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1 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), CSSI, OD, NCI, NIH

2 In the U.S., Cancer Continues to Represent an Enormous Burden 569,490 Americans died of cancer in ,529, Americans will be diagnosed d with cancer this 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 Rates Per 100,00 00 Americans 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.

3 Global Burden: By 2020, Cancer Mortality 10 M/yr (Incidence 16 M/yr) Source: IACR, WHO

4 Limited Progress in Reducing Cancer Death Rate 600 Mortality (Per 100,0 000 Age Adjusted) Cancer Heart War on Cancer 4

5 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 physics, not just the 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

6 Including Unique Perspectives Shigeo Fukuda

7 Including Unique Perspectives that Add Insight Shigeo Fukuda

8 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? 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 both perspectives yields a more comprehensive (clearer) picture of what cancer is and how it functions at all levels especially at the sub-molecular/atomic scales

9 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

10 PS-OC Network: Physical scientists & cancer biologists/oncologists integrated from the start g g g Liphardt Weaver O Halloran Licht Shuler Hempstead van Oudenaarden Jacks UC Berkeley Northwestern Cornell MIT Hillis Agus USC Scripps Kuhn Bethel PS-OC Network Michor Holland DFCI Princeton Austin Tlsty ASU TMHRI Moffitt Johns Hopkins Davies Grady Ferrari Curley Gatenby Gillies Wirtz Semenza

11 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

12 PS-OC Operation: Interactions Inside and Outside of Network Project 1 Core A Project 2 PS-OC Network Project 3 Education and Training Unit PS-OC Organizing Framework Core B Project 4 Pilot Projects Outreach and Dissem Unit Trans-Network Admin Unit Outreach Projects External Research Communities Trainee Exchange Trans- Network Projects Education and Training Unit Core A Project 1 Core B Project Project Project Pilot Projects Organizing Framework PS-OC Trans-Network Admin Unit Outreach and Dissem Unit Outreach Projects

13 Tumor, Cancer, and Metastasis >90% of deaths is ca sed b >90% of deaths is caused by disseminated disease or metastasis

14 Cancer: A Disease of the Genes! an Serous ovaria Lung squamo ous GBM GBM: 400 cases, Lung squamous: 113 cases, Serous ovarian : 486 cases

15 Cancer: A Disease of Pathways!

16 Cancer: A Disease of Biomarkers and Microenvironment! Phosphoprotein Expression and Postsurgical Ischemia: pmapk Immunostaining (Ventana) Case A Case B 10 min Change of pmapk expression after min cold ischemia 20 min 60 min Slide Compliments of Dr. Hartmut Juhl, Indivumed GmbH, Hamburg

17 Perspective: Critical to Think in Terms of Space and Time

18 Theme: Physical Laws and Principles New Conceptual Approaches Biology is not exempt from physical laws and principles Force Force Forces (shear, compressive, pressure, etc.) are experienced by metastatic cells Force Force Force Quantify, catalog, and determine impact and outcomes of forces Primary tumor leak cancer cells into vasculature and establish secondary sites Well-known to be an inefficient process (0.01%) ~1 million cells per day!

19 Cell Mechanics: An Emerging Field With Potential Intersection with Cancer Manuscripts Citations Statistics generated using Web of Science with keywords cell mechanics and cancer

20 PS-OC Network Research: Cell Mechanics MDA-MB single MDA-MB confluent MDA-MB-231 in MCF10A Velocity JHU & ASU PS-OCs Biophysical Journal, Volume 102, Issue 12, , 20 June 2012 UC Berkeley PS-OC Proc Natl Acad Sci U S A v.109(6); Feb 7, 2012

21 PS-OC Network Research: CTC Technology Scripps PS-OC Editorial & 5 articles in Physical Biology, Vol 9, February 2012 All 103 circulating tumor cells identified on 1 slide from a Stage IV prostate Fluid Biopsy in Patients with Metastatic Prostate, Pancreatic and Breast Cancers, Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors Cytometric comparisons between circulating tumor cells from prostate cancer patients and cancer the patient. prostate tumor derived LNCaP cell line High definition imaging of circulating tumor cells and associated cellular events in non-small cell lung 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 Scripps: 1129 CTC/7.5ml Veridex: 1 CTC/7.5ml Cornell PS-OC PLoS One. 2012;7(4):e Epub 2012 Apr 27.

22 PS-OC Network Research: DNA Mechanics Northwestern PS-OC Nature Jun 3. doi: /nature DFCI PS-OC Nature Biotechnology 29, (2011) MIT PS-OC Nature Biotechnology 29, (2011)

23 Biomaterials in Cancer Research Tools to develop a deeper understanding of cancer cell adhesion, migration, and extracellular matrix remodeling Tepuis Princeton PS- OC 3D Hydrogels JHU PS- OC Fraley SI et al. Nature Comm Liu L et al. PNAS 2011

24 OPSO Website Contains Relevant Active Funding Opportunities

25 PS-OC Funding Opportunity: PS-OC Pilot and Outreach Pilot Project Opportunities Cornell University PS-OC (Outreach Pilot projects) Johns Hopkins University PS-OC (Pilot projects with a JHU collaborator) Northwestern University PS-OC (new Pilot and Outreach Pilot opportunities expected Spring 2013) /f / Princeton University PS-OC (Pilot Projects with evolution focus)

26 PS-OC Funding Opportunity: NCI/NSF Collaboration Physics and LIfe Sciences Early Research (PLIER) Awards Release Date: Closed Feb. 15 NSF Award Amount: $125 K for 3 years Expected #Awards: 5 6 Public Program Announcement

27 Relevant Active NIH Funding Opportunities Transforming Biomedicine at the Interface of the Life and Physical Sciences (R01) PAR [NIGMS/NIAMS/NIBIB] Nanoscience and Nanotechnology in Biology and Medicine ( R01, R21) PA , PA [Issued by NIBIB] Development of Multifunctional Drug and Gene Delivery Systems (R01) PAR [Issued by NIBIB] Early Stage Innovative Technology Developments in for Cancer Research (R21) RFA-CA [NCI] Use RePORTER ( to find collaborators, evaluate the status of research fields, find receptive ICs and study sections

28 Learn More about PS-OCs: ( cancer More Information Jonathan Franca-Koh, Ph.D. Program Manager, PS-OC ih Larry Nagahara, Ph. D. Director, OPSO