Assessment of Physical Sciences and

Engineering Advances in Life Sciences and

Oncology (APHELION Study)

Physics and oncology/biomedical Physics and oncology/biomedical

studies in Asia

June 2013

Purpose of APHELION Study• Compare U.S. R&D and status with those in

Asia and Europe

• Identify the gaps and barriers in working with leading centers in Asia and Europe

• Identify the major innovations emerging • Identify the major innovations emerging abroad

• Guide U.S. research investments

• Look for opportunities for cooperation and collaboration

World Technology Evaluation Center, Inc. (WTEC)

WTEC is conducting a global Assessment of Physical Sciences and Engineering Advances in Life Sciences and Oncology (APHELION), sponsored by the U.S. government.

WTEC is the leading organization in the U.S. conducting International Technology Assessments via expert review, and has conducted over 70 such studies since 1989

HTTP://WWW.WTEC.ORG/APHELION

Sponsors of APHELION Study

• National Institutes of Health (NIH/NCI): – NCI Sponsor: Larry Nagahara and Nas Kuhn

– NIBIB Sponsor: Christine Kelley

– NIH NCI Participants: Larry Nagahara, Nas Kuhn, Sea n Hanlon

• National Science Foundation (NSF):– Sponsors: Clark Cooper; Semahat Demir; Kesh Narayan an,

M. C. Roco,

““““New Biology”””” –

2009 ““““Intersection of the Physical

& Life Sciences –

2010

A“Conference on Research at the Interface of the Life andPhysical Sciences: Bridging the Sciences” was conductedon November 9, 2004, in Bethesda, MD. The meeting,sponsored by NIH/NIBIB and NSF, to obtain communityinput on how to bridge the life and physical sciences.

Merging Physical & Life Sciences

“Bringing physics, not just the physicists, to biology””””– Harold Varmus, NIH DirectorCentennial Speech, APS March Meeting, 1999“In biomedicine,…we can harness the historic convergence between life sciences and physicalsciencesthat's underway today; undertaking public projects -- in the spirit of the Human GenomeProject -- to create data and capabilities that fuel discoveriesin tens of thousands of laboratories;and identifying and overcoming scientific and bureaucratic barriers to rapidly translating scientificbreakthroughs into diagnostics and therapeutics that serve patients…”– President Obama,NAS Speech, April 2009

NCI Interest - Leveraging the Physical Sciences for New Frontiers in Oncology

2008 2009

Spring Summer Fall Winter Spring Summer

NRC convened 16 panelist on ““““New Biology””””

Fall

NRC published –““““New Biology””””

~300 extramural participants

NCIBSA

RFA Apps Review

Outcomes from Workshops Establish trans-disciplinary physical sciences-oncology centers Composed of integrated physical sciences-oncology teams Focus on theme(s) for center frameworkCenters led by physical scientist with senior co-investigator from oncology

Award

Merging “ Perspectives ”

Physical Scientist Cancer Biologist/Oncologist

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 cell, molecule, tissue is it?What changed?What’’’’s up/down regulated?Do I see the same thing in several tumors?

How much time does it take?What are the spatialeffects?

Different ‘‘‘‘views’’’’ of the same pictureHaving 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

Delegation for the APHELION Study Site Visits

• US government sponsors and officials

• Members of Expert Panel

• WTEC staff

APHELION Panelists Paul Janmey (Chair) , PhD, Professor of Physiology, School of Medicine,

University of Pennsylvania;

Daniel A. Fletcher, PhD Professor, Department of BioengineeringUniversity of California ,Berkeley;p

Sharon Gerecht, PhD, Associate Professor, Department of Chemical and Biomolecular Engineering, Johns Hopkins University;

Ross Levine, MD, Memorial Sloan-Kettering Cancer Center;Ross Levine, MD, Memorial Sloan-Kettering Cancer Center;

Parag Mallick , PhD, Assistant Professor, Department of Radiology, Stanford University;

Owen McCarty , PhD, Associate Professor, Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University;

Cynthia Reinhart-King , PhD, Associate Professor, Department of Biomedical Engineering, Cornell University.

APHELION Expert Advisors

• Antonio Tito Fojo, M.D., Ph.D.

Medical Oncology Branch and Affiliates

Head, Experimental Therapeutics SectionSenior Investigator Building 10, Room 12C103

• Denis Wirtz,

Professor of Chemical and Biomolecular Engineering and Materials Science, Johns Hopkins University

Current and past research:•Interaction between cytoskeletal and ECM stiffness

•Effects of substrate mechanics of cell structure and function

•Phosphoinositide signaling for actin assembly

•Fibrin-based materials for wound healing

•Intermediate filament assembly and mechanics

Paul Janmey

Biopolymer physics

Cell and soft tissue

mechanics

Extracellular matrix structure

and signaling

APHELION Panelists

Fib

robl

asts

M

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tes

Biography:

Professor, Physiology, Physics, Bioengineering

Institute for Medicine and Engineering

University of Pennsylvania

Post-Doc Hematology-Oncology Unit, MGH

PhD, Physical Chemistry – Univ. Wisconsin

AB, Philosophy, Oberlin College

New research directions• Signaling between integrins and HA receptors for

cell proliferation and motility

• Mechanosensing through cadherins

Web: http://www.uphs.upenn.edu/ime/janmey/index.html

Fib

robl

asts

M

yocy

tes

Current and past research:•Mechanics of leukemic cells

•Reconstitution of branched actin networks

•Measurement of platelet contraction

•Mechanics of branching morphogenesis

Dan Fletcher

Cell mechanics,

reconstitution of the

cytoskeleton, optical & force

microscopy, global health

technologies

APHELION Panelists

Biography:

Professor, Bioengineering and Biophysics,

University of California, Berkeley

Faculty Scientist, Physical Biosciences, Lawrence

Berkeley National Laboratory

PhD – Stanford University

DPhil – Oxford University

BS – Princeton University

New research directions• Mechanics of breast cancer cells

• Mechanical regulation of actin networks

• Development of infectious disease diagnostics

Web: http://fletchlab.berkeley.edu

Current and past research:•Stem Cell Engineering

•Biomaterials

•Angiogenesis and vascular biology

•HypoxiaSharon Gerecht

Blood vessel development and

differentiation, hypoxia,

Polysaccharide hydrogels,

Wound healing

APHELION: Expert Panelist

Blood, 2012; Biomaterials, 2012; SCTM 2013

Biography:

Associate Professor, Chemical and Biomolecular

Engineering, Johns Hopkins University

PhD – Biotechnology- Technion-Technical Institute of

Israel

MS – Medical Science – Tel Aviv University

BA - Biology- Technion-Technical Institute of Israel

Web: http://www.jhu.edu/chembe/gerecht/

New research directions• Tumor ECM

• Burn and diabetic wound healing

• Blood brain barrier

PDMS

Glass

PMMA

Biomed Microdevices, 2012; Biotechnol Appl Biochem, 2012

Current and past research:•Markers and Mechanisms of Therapeutic Response to

EGFR Targeted Therapies

•Models of tumor-to-circulation transmission

•ProteoWizard

•Systems models of cell-state

Parag Mallick

Biomarkers for diagnosis and

prognosis, Systems biology,

Proteomics, Multi-scale

models of cellular regulation,

applications of micro-devices

for single-cell analysis

APHELION Panelists

Biography:

Asst. Professor, Radiology, Bio-X, Canary Center for Cancer

Early Detection

Stanford University

Post-Doc, Clinical Proteomics & Systems Biology

– Institute for Systems Biology

PhD, Chemistry – UCLA

BS, Computer Science – Washington University

New research directions• Tumor evolution

• Cell Biomechanics

• Tumor Microenvironment

Web:

http://med.stanford.edu/profiles/Parag_Mallick/

Current and past research:•Characterization of the interaction of cancer cells with

the blood microenvironment

•Development of anti-thrombotic strategies

•Role of Rho GTPases in platelet cell biology

Owen McCarty

Blood cell biology, circulating

tumor cells, cancer

metastasis, thrombosis

APHELION Panelists

Biography:

Associate Professor, Biomedical Engineering

Oregon Health & Science

University

Postdoc – Pharmacology, Oxford University

PhD – Chemical Engineering, Johns Hopkins

University

BS – Chemical Engineering, SUNY Buffalo

New research directions• Development of single cell imaging modalities

• Identification of thrombotic risk factors in cancer

patients

Web: www.ohsu.edu/bme

Current and past research:•Cell Migration

•Cell-Biomaterial Interactions

•Cellular Traction Stresses

•Cellular Mechanotransduction

Cynthia Reinhart-King

Cancer metastasis,

Angiogenesis, Atherosclerosis

progression

APHELION Panelists

Biography:

Associate Professor, Biomedical Engineering, Cornell

University

PhD, Bioengineering, University of Pennsylvania

SB, Chemical Engineering, MIT

SB, Biology, MIT

New research directions• Microfabricated tissue structures

• 3D Microenvironments

• Microfluidic devices for cellular studies

Web: http://cellmechanics.org

APHELION Expert Advisor

Antonio Tito Fojo, M.D., Ph.D.

Medical Oncology Branch and Affiliates

Head, Experimental Therapeutics SectionSenior Investigator Building 10, Room 12C10310 Center DriveBethesda, MD 20892

Phone: 301-496-2631

Fax: 301-402-1608 E-Mail: fojot@mail.nih.gov

17

Biography

Dr. Fojo was born in Havana, Cuba, moved to the United States with his family in 1960, and became a U.S. citizen in 1970. He received his M.D. and Ph.D. from the University of Miami. He completed 3 years of training in internal medicine at Washington University/Barnes Hospital in St. Louis, and after a year as chief resident came to the NCI as a clinical associate in the Medicine Branch, now the Cancer Therapeutics Branch. After 3 years with Drs. Ira Pastan and Michael Gottesman, he assumed the position of senior investigator in the Cancer Therapeutics Branch.

Denis WirtzJohns Hopkins UniversityEmail: wirtz@jhu.eduWebsite: http://www.jhu.edu/chembe/wirtz/ he Department of Chemical and

EXPERT ADVISOR

Denis Wirtz is professor of Chemical and Biomolecular Engineering and Materials Science

18

Denis Wirtz is professor of Chemical and Biomolecular Engineering and Materials Science in the Whiting School of Engineering and a member of the oncology department at the Johns Hopkins School of Medicine. Dr. Wirtz is a recognized expert in cell and molecular biophysics and in the development of new methods grounded in physical principles, including statistical mechanics and polymer physics, to probe and establish the physical mechanisms of cell motility, intercellular adhesion, and microrheology. He is Editor-in-Chief of Cell Health and the Cytoskeletonandserves on the Editorial Boards of Biophysical Journal, Physical Biology, and Cell Adhesion and Migration. He is the founder and Associate Director of the Johns Hopkins Institute for NanoBioTechnology (INBT).

Scientific/Technical Topics of Interest

• Information Transfer in Cancer and other Biomedical research areas through an Evolutionary Lens

• Time Domain of Cancer Metastasis and other Diseases with Therapy

• Mechanics in Health and Disease

• Physical Parameters of Cells, Microenvironment, and Host

• Understanding Physical Emergent Properties During Pathogenesis of Disease

• Heart and Lung Disease – Connections to Cancer

• Physics of New Diagnostic Principles and Methods

APHELION Europe Sites Visitedhttp://wtec.org/aphelion/index.php

• FRANCE�Institute Curie, Paris�University of Paris Diderot

• GERMANY• GERMANY�Max Planck Institute (Dresden, Gottingen)�Dresden Technical University�Gottingen University�Technical University of Munich�University of Heidelberg�University of Leipzig�University of Rostock

APHELION Europe Sites Visited (2)

• ISRAEL�Weizmann Institute�Technion University

• ITALY�University of Padua�University of Padua�University of Milan�European Institute of Oncology

• The NETHERLANDS�The Hubrecht Institute, Utrecht�Radboud University Nijmegen �The University of Leiden

APHELION Europe Sites Visited (3)• SPAIN�University of Barcelona�University of Basque Country

• SWITZERLAND�Ecole Polytechnique Federal de Lausanne (EPFL)�Ecole Polytechnique Federal de Lausanne (EPFL)�University of Basel

• SWEDEN�Uppsala University�The Karolinksa Institute �The Royal Institute of Technology

APHELION Asia Study Tour Delegation

Group A (Singapore, Shanghai, Taiwan, Japan):

Paul Janmey (Chair), Daniel Fletcher*, Sharon Gerecht*, Owen McCarty*, Cynthia Reinhart-King, Nas Kuhn, Larry Nagahara *+ …King, Nas Kuhn, Larry Nagahara *+ …

Group B (Beijing, Hong Kong, Japan):

Daniel Fletcher*, Sharon Gerecht*, Parag Mallick, Owen McCarty*, Larry Nagahara*, Sean Hanlon+ …

APHELION Tentative Schedule• Feb 2012 – Kickoff meeting

• May 2012 – Visit to Europe

• June 2012 – European draft reports

• June 2012 – Final workshop at NIH (http://www.tvworldwide.com/events/nih/120612/)(http://www.tvworldwide.com/events/nih/120612/)

• August 2012 – Final report goal

• June 2013 – Visit to Asia

• July 2013 – Asian site reports

• October 2013 – Draft report

• November 21, 2013 – Final workshop in Washington DC

• February 2014 – Final report goal

APHELION Final Workshop

• To be held in Washington, D.C. on November 21, 2013

• Final workshop will be webcast from 8:00 am • Final workshop will be webcast from 8:00 am to 4:30 pm EDT

• Registration information for final workshop will be at http://www.wtec.org/aphelion

Thank you for your cooperation in this visit!in this visit!