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Intercellular Interactions Modulate Carcinogenesis Course: A Dynamic System Study

Award Number: U54CA149233
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2010
PERIOD OF PERFORMANCE END DATE: 02/28/2015

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Intercellular Interactions Modulate Carcinogenesis Course: A Dynamic System Study - DESCRIPTION (provided by applicant): To study cancer, very powerful modern experimental methods -- including high-throughput approaches -- and modern statistics/computer-science methods are now used. Mechanistic quantitative models of cancer time-development, from very early stages to clinical disease, have been somewhat less well explored. A highly interdisciplinary, unusually closely interacting team of cancer biologists, molecular biologists, mathematicians, physicists, and computer scientists has been assembled to work toward dynamic, mechanistic carcinogenesis models so parsimoniously parameterized they have predictive capability. The overriding goal is to make the models more realistic and credible by taking into account the influence of intercellular interactions during carcinogenesis. The time-course of effects involving a diverse, interacting cell population and/or of tumor progression, a comparatively late stage in the lengthy cancer latency period, will be emphasized. The phenomena of microscopic tumor dormancy, recently found to be almost ubiquitous in humans, and of emergence from dormancy due to "switching on" of blood supply recruitment, will be one main focus. The team will work under an iterative paradigm: experiments, mathematical/computational model, experiments, etc. Data will be gathered from various sources: in vitro experiments, including modern high throughput results, and in depth studies of particular proteins; experiments using genetically engineered mice; highly developed imaging approaches; and results in the literature on human cancer incidence or mortality. Several of the individual projects will involve ionizing radiation, a carcinogen whose action has been unusually well characterized at very small time and length scales, as well as over a whole human lifetime and for whole organisms, so that it is highly informative about cancer development in general. Mathematical methods will include the following: classic mathematical biology approaches with systems of ordinary or partial differential equations; modern discrete and hybrid discrete-continuous models based on treating many cells, each represented as an entity which can interact with other cells and with its microenvironment according to comparatively simple rules, with complicated whole-system behavior arising from those rules; probabilistic "stochastic-process" models, needed since most new stages of cancer evolution putatively originate with a single cell at risk for eradication or accidental extinction; and multi time-scale computational modeling, in which effects governed by comparatively very short time scales influence much longer time-scale cancer evolution and vice-versa.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2014	GENESYS RESEARCH INSTITUTE INC	77 WARREN STREET	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	000	5	4/23/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $1,350,267 )
2014	2014	GENESYS RESEARCH INSTITUTE INC	77 WARREN STREET	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	000	5	4/3/2014	NON-COMPETING CONTINUATION	$1,252,825
2014	2014	GENESYS RESEARCH INSTITUTE INC	77 WARREN STREET	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	001	5	4/24/2014	NON-COMPETING CONTINUATION	$97,442
														Subtotal = $1,350,267

Issue Date FY: 2013 ( Subtotal = $1,344,937 )
2013	2013	GENESYS RESEARCH INSTITUTE INC	77 Warren Street	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	001	4	7/1/2013	NON-COMPETING CONTINUATION	$696,700
2013	2013	GENESYS RESEARCH INSTITUTE INC	77 Warren Street	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	002	4	7/12/2013	NON-COMPETING CONTINUATION	$8,405
2013	2013	GENESYS RESEARCH INSTITUTE INC	77 Warren Street	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	000	4	3/20/2013	NON-COMPETING CONTINUATION	$639,832
														Subtotal = $1,344,937

Issue Date FY: 2012 ( Subtotal = $1,442,491 )
2012	2012	GENESYS RESEARCH INSTITUTE INC	77 Warren Street	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	000	3	8/27/2012	NON-COMPETING CONTINUATION	$1,442,491
														Subtotal = $1,442,491

Issue Date FY: 2011 ( Subtotal = $1,641,180 )
2011	2011	GENESYS RESEARCH INSTITUTE INC	77 Warren Street	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	001	2	6/22/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$65,931
2011	2011	GENESYS RESEARCH INSTITUTE INC	77 Warren Street	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	002	2	8/19/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$153,900
2011	2011	GENESYS RESEARCH INSTITUTE INC	77 Warren Street	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	000	2	4/5/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,421,349
														Subtotal = $1,641,180

Issue Date FY: 2010 ( Subtotal = $1,556,606 )
2010	2010	CARITAS ST ELIZABETH`S MEDICAL CENTER OF BOSTON	736 CAMBRIDGE ST, BOX OLH-6BD	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	001	1	9/3/2010	SUPPLEMENT FOR EXPANSION	$25,000
2010	2010	CARITAS ST ELIZABETH`S MEDICAL CENTER OF BOSTON	736 CAMBRIDGE ST, BOX OLH-6BD	BOSTON	MA	02135	SUFFOLK	USA	Cancer Centers Support Grants	000	1	5/1/2010	NEW	$1,531,606
														Subtotal = $1,556,606

Grand Total All Awards = $7,335,481

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Intercellular Interactions Modulate Carcinogenesis Course: A Dynamic System Study

Award Number: U54CA149233

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2010

PERIOD OF PERFORMANCE END DATE: 02/28/2015

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