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Combining systems biology and structural biology to find new therapeutics

Award Number: R01GM102365
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2012
PERIOD OF PERFORMANCE END DATE: 03/31/2022

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Combining systems biology and structural biology to find new therapeutics - Abstract Abstract of funded award: Our accelerating ability to measure biological systems at the molecular, cellular, organ and organism level promises a new generation of powerful and improved drug therapies. However, drug failures continue to occur at high rates due to lack of efficacy or unexpected toxicity—even when the drug binds its intended target with very high affinity. We do not sufficiently understand the biological systems in which we are intervening, suggesting that we are making fundamental assumptions that are wrong. Building on results from our previous grant period, this renewal proposal proposes new assumptions: (a) when drugs work it is because they interact not only with their target but with many other off-targets that produce synergistic effects, (b) the actions of drugs can be best understand as the interaction between protein networks that are dysfunctional in disease and drug response networks that are modulated by the complete set of relevant targets, and (c) that evidence of direct physical interaction is superior to complicated and integrative signals (such as gene expression) in creating and analyzing drug response networks that can usefully be linked to disease networks. Thus, we propose a plan to (1) develop and apply methods to predict drug interactions on a proteome scale, and uses these to improve methods for creating interaction networks relevant to drug response and disease biology, (2) devise methods to associate drug response with disease biology, using the features of the associated protein networks, and (3) collaborative apply these tools with collaborations from academia (U. Pennsylvania for NSAID response & the Structural Genomics Consortium for target selection and triage), industry (Genentech for cancer, Pfizer for autoimmune disease), and government (the U.S. FDA for seeking biomarkers to predict efficacy and toxicity. With success, we will have created a framework for drug discovery, repurposing, combination use and toxicity prediction that may contribute to a higher rate of success in delivering new therapies to benefit public health.


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: 2024 ( Subtotal = -$3,751 )
2024	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	8	1/13/2024	SUPPLEMENT FOR EXPANSION	-$784
2024	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	8	1/13/2024	NON-COMPETING CONTINUATION	-$2,967
														Subtotal = -$3,751

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	8	8/22/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $460,440 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	8	8/31/2021	SUPPLEMENT FOR EXPANSION	$96,200
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	8	3/24/2021	NON-COMPETING CONTINUATION	$364,240
														Subtotal = $460,440

Issue Date FY: 2020 ( Subtotal = $378,506 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	7	6/2/2020	SUPPLEMENT FOR EXPANSION	$14,266
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	7	3/4/2020	NON-COMPETING CONTINUATION	$364,240
														Subtotal = $378,506

Issue Date FY: 2019 ( Subtotal = $363,928 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	6	3/20/2019	NON-COMPETING CONTINUATION	$363,928
														Subtotal = $363,928

Issue Date FY: 2018 ( Subtotal = $363,205 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	5	4/3/2018	COMPETING CONTINUATION	$363,205
														Subtotal = $363,205

Issue Date FY: 2017 ( Subtotal = -$335 )
2017	2015	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	4	8/15/2017	NON-COMPETING CONTINUATION	-$335
														Subtotal = -$335

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2015	STANFORD UNIVERSITY	616 SERRA STREET	STANFORD	CA	943056215	SANTA CLARA	USA	Biomedical Research and Research Training	000	4	7/18/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $352,680 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	4	5/6/2015	NON-COMPETING CONTINUATION	$352,680
														Subtotal = $352,680

Issue Date FY: 2014 ( Subtotal = $419,379 )
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	2	4/30/2014	SUPPLEMENT FOR EXPANSION	$11,208
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	001	3	5/30/2014	NON-COMPETING CONTINUATION	$408,171
														Subtotal = $419,379

Issue Date FY: 2013 ( Subtotal = $339,274 )
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	2	5/23/2013	NON-COMPETING CONTINUATION	$339,274
														Subtotal = $339,274

Issue Date FY: 2012 ( Subtotal = $338,227 )
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Biomedical Research and Research Training	000	1	8/14/2012	NEW	$338,227
														Subtotal = $338,227

Grand Total All Awards = $3,011,553

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Combining systems biology and structural biology to find new therapeutics

Award Number: R01GM102365

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2012

PERIOD OF PERFORMANCE END DATE: 03/31/2022

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