# Undergraduate Summer Research Experiences Support for Combining systems biology and structural biology to find new therapeutics

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $14,266

## Abstract

Abstract
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.

## Key facts

- **NIH application ID:** 10145956
- **Project number:** 3R01GM102365-07S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** RUSS BIAGIO ALTMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $14,266
- **Award type:** 3
- **Project period:** 2012-09-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145956

## Citation

> US National Institutes of Health, RePORTER application 10145956, Undergraduate Summer Research Experiences Support for Combining systems biology and structural biology to find new therapeutics (3R01GM102365-07S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10145956. Licensed CC0.

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