# Presentation: 359837

## Innovative Molecular Analysis Technologies (IMAT) for Cancer Program

**Presentation to:**
** ****NCI National Cancer Advisory Board**
**September 7, 2006**

## Agenda

**Greg Downing, D.O., Ph.D. ***Director, Office of Technology and Industrial Relations*“Overview of the Innovative Molecular Analysis Technologies  (IMAT) for Cancer Program”
**Stephen J. Kron, M.D., Ph.D.***Associate Professor, Molecular Genetics and Cell Biology, **University of Chicago*
- 	“Developing Tests for Bcr-Abl Activity and Gleevec Resistance  in CML Patients”
**Jan E. Schnitzer, M.D.***Scientific Director, Sidney Kimmel Cancer Center*
*	*“Proteomic Mapping of Blood Vessel Surfaces and Caveolae In Vivo to Improve Antibody Penetration, Imaging and Therapy of Solid Tumors** **”
** **

## IMAT Mission and Goals

**Mission:  **
- To develop and apply new technologies that transform researchers’ abilities to identify molecular changes that distinguish pre-cancerous and cancerous cells from normal cells.

**Goals:**
- To focus innovative technology development on cancer
- To solicit highly innovative technology development projects from the scientific and medical communities
- To accelerate the maturation of meritorious technologies from feasibility to development and/or commercialization.

## Why the IMAT Program Was Initiated

**Established in 1998 to encourage highly innovative cancer technology development projects that: **
- Address the complexity of cancer, including myriad molecular and cellular processes
- Understand relevant genes and roles of nucleic acids, proteins, and other cellular factors and modifications
**Provides novel mechanisms, program, and review structures to:**
- Support innovative cancer-relevant technology from inception
- Support development of novel applications of those technologies that uniquely enable cancer biology research by R01 investigators
**Ensures that resulting technologies are robust and appropriate for intended applications in basic, preclinical, and clinical settings**

## Attributes of the IMAT Program

**High-risk, high-impact**
**Emphasis on technology development vs. hypothesis-driven research**
**Milestone-based, with milestones that address quantitative measures of specificity, sensitivity, speed, and other performance parameters**
**Staged process requiring quantitative evidence of progress before advancing to next stage**
**Some IMAT funding opportunities directed at small businesses under SBIR and STTR; since inception, ~ 1/4 of applications and ~ 1/3 of awards for small businesses**

## Life Cycle of an IMAT Technology Development Project

**Projects are staged from:**

**R21/Phase I**

**R33/Phase II**

**Mechanism:**
- Exploratory/pilot phase; requires innovative technology/approach; no preliminary data required

**Mechanism:**
- Developmental phase; requires feasibility data

**Requirements:**
- Description of study
- Relevance to cancer
- Quantitative milestones
- Novel research tool, new detection methodology, or treatment technology
- Improvement over state-of-the-art

**Requirements:**
- Plan for developing the technology
- Description of potential impact
- Description of completed milestones or evidence of technical feasibility

**Technology Dissemination via:**

- NCI Programs and Initiatives
- Collaboration
- Publication
- Licensing
- Commercialization

**Technology Tools for Researchers:**

- Gene expression arrays
- Clinical specimen preservation
- Ultra-high-throughput molecular detection
- Multi-dimensional protein identification
- Photo-stable labels

## IMAT Development Pathway

**Innovations in Cancer Sample Preparations**

**Innovative Technologies for ****the Molecular Analysis of Cancer**

**Application of Emerging Technologies for Cancer Research**

**NCI Biological and Clinical Research Programs, Public/Private Partnerships, or Commercialization**

**Technologies, Approaches, and Knowledge to Understand, Prevent, Detect, Diagnose, and Treat Cancer**

**IMAT**

## IMAT Review Process  

**Focus on technology development vs. hypothesis-driven research**
**Milestones reviewed and improvements recommended**
**Focus on whether technology is an improvement over state-of-the-art**
**Review continuity by using previous IMAT panel members and ****IMAT grantees**

## Case Studies

**Jonathan D. Oliner, Ph.D., *****Affymetrix***
**IMAT Award:**  Reverse-Engineering Signal Transduction
- 	Networks *(1998) *
**Impact:  **Gene expression arrays allow researchers to follow the downstream effects of perturbations to biochemical pathways or networks by highlighting changes in gene expression

**GeneChip® CustomSeq® Resequencing Arrays**

## Case Studies

**Gary Latham, Ph.D., *****Ambion, Inc.***** **
**IMAT Award: **Enzymatic Tools for Degrading Tissue and Preserving RNA *(2001)** *
**Impact:** Researchers can store tissue samples without significant loss of RNA integrity

## Case Studies

**John R. Yates, Ph.D., *****University of Washington/Scripps***
**IMAT Award:** Direct MS Analysis of Complex Protein Mixtures *(1999)** *
**Impact:** The MudPit (multi-dimensional protein identification technology) platform marks the transition from traditional 2-D gel electrophoresis to 2-D liquid chromatography

## Case Studies

**Mark Chee, Ph.D., *****Illumina, Inc.***
**IMAT Awards:**
- Gene Expression Analysis on Randomly Ordered DNA Arrays *(1998)*
- Parallel Array Processor *(1998)*
- Protein Profiling Arrays *(1999)** *
**Impact:** The ultra-high-throughput Illumina bead platform allows researchers to simultaneously assay over 100,000 points for gene expression, alternative splice detection, and protein expression

## Case Studies

**Dave Krizman, Ph.D., *****Expression Pathology***
**IMAT Award:** Protein Arrays for Molecular Analysis of Cancer Tissue *(2002)** *
**Impact:** New technology that permits effective, high-throughput discovery and analysis of protein biomarkers in formalin fixed paraffin embedded (FFPE) tissue

## Case Studies

**Robert H. Daniels, Ph.D., *****Quantum Dot Corp. (Invitrogen)***
**IMAT Award:** Sensitive, Multiplexed Analysis of Breast Cancer Markers *(1999)** *
**Impact:** Quantum dots (semi-conductor nanocrystals) are photostable labels that emit extremely bright light in a range of colors enabling researchers to monitor complex interactions within living cells or *in situ *on tissue microarrays

## Next-Generation Technology: Overcoming Technical Barriers to Research Productivity

**Protein**

**Nucleic Acid**

**Molecular Interactions**

** ****Micro RNAs**
** ****RNAi**
** ****Epigenomics**
** ****Alternative Splicing**
** ****Genomic Regulatory Factors**
** ****Mutation Detection**

- Increased Sensitivity
- Improved Labeling Tools
- Increased Throughput
- Reduced Cost
- More Quantitative
- Single Molecule/Cell
- Reduced Sample Size
- Rare Entity Isolation
- Parallel Processing

** ****Pathways and Networks**
** ****Transient Complexes**
** ****Real-time Macro Molecular Interactions**
** ****Metabolite Detection/Quantification**

**Localization**
**Fractionation and Quantitation**
**Identification of Low****Abundance and Transient Proteins**
**Small Molecule Interactions**
**Protein/Protein Interactions**
**Structure/Function Modifications**

_**Paradigm Shift**_

**Molecular Device/Chemistry**

-  **Nanotechnology**
** ****Microfluidics**
** ****Surface Chemistries**
** ****Sensors**
** ****Platform Integration**

## Program Management Team

**Program Managers:**
- Office of Technology and Industrial Relations:
**	****Greg Downing, D.O., Ph.D.,** *Program Director*
- 	**Richard Aragon, Ph.D.,** *Project Manager*
- Division of Cancer Biology:
- 	**Jennifer Couch, Ph.D. ****J. Randy Knowlton, Ph.D.**
- Division of Cancer Prevention:
- 	**Paul Wagner, Ph.D.**
**	****Sudhir Srivastava, Ph.D., M.P.H.**
- Division of Cancer Treatment and Diagnosis:
**	****Jim Jacobson, Ph.D.**
**	****Rebecca Huppi, Ph.D.**
**	****Avraham Rasooly, Ph.D.**** **
- Division of Cancer Control and Population Sciences:
- 	**Carol Kasten, M.D. **

## http://imat.cancer.gov