Researchers at the Icahn School of Medicine at Mount Sinai have received more than $31 million from the National Institutes of Health (NIH) to create three new centers that will study how drugs interact with human cells to increase their effectiveness and decrease side effects.
A new Drug Toxicity Signature Center will be run by Ravi Iyengar, PhD, Dorothy H. and Lewis Rosenstiel Professor, Department of Pharmacology and Systems Therapeutics, who has received a grant totaling $11.6 million from the NIH. By leveraging the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System database, the center will develop cell signatures that can be used to predict the effects of certain drugs and drug combinations.
Mount Sinai was one of five U.S. research institutions chosen to develop centers that contribute to the second phase of the NIH Common Fund project, known as the Library of Integrated Network-based Cellular Signatures (LINCS).
In a separate-but-related grant, the NIH has awarded $19.8 million to Principal Investigator Avi Ma’ayan, PhD, Associate Professor in Mount Sinai’s Department of Pharmacology and Systems Therapeutics to coordinate and integrate the data generated by Dr. Iyengar’s new center and the other research centers. Dr. Ma’ayan’s computational team, along with teams at the University of Miami and the University of Cincinnati, will design new ways to analyze and visualize the data so that it serves as a national and international resource. Dr. Ma’ayan received his PhD from the Icahn School of Medicine in Dr. Iyengar’s laboratory.
Dr. Iyengar’s center will focus on three serious side effects of drugs: heart failure, liver damage, and peripheral neuropathy. “We are developing heart, liver, and nerve cells from stem cells for normal adult subjects and will be studying how these cells react to drugs to accelerate the discovery of new therapies and create predictive computer models to improve treatment,” he says.
Along with Dr. Iyengar, the principal investigators of the center grant are Eric Sobie, PhD, BSE, Associate Professor of Pharmacology and Systems Therapeutics; and Marc Birtwistle, PhD, BS, Assistant Professor of Pharmacology and Systems Therapeutics.
“Can we develop drugs and drug combinations to effectively treat and mitigate risks and side effects for patients with progressive diseases such as cancer and heart disease?” asks Dr. Iyengar. “Can we develop computational models that will allow us to understand cellular functions in different tissues in response to drugs? This center will enable us to answer those questions to improve current therapies and create new ones.”
Research laboratories at Harvard Medical School; Oregon Health and Science University; Broad Institute of the Massachusetts Institute of Technology and Harvard University; and the University of California, Irvine, were also chosen by the NIH to be part of the LINCS consortium to create data generation centers that bridge the gap between clinical data and molecular networks.
Says Dr. Ma’ayan, “We have much work to do in harmonizing, analyzing, and visualizing the masses of data collected by so many NIH-funded centers, but the combined effort promises to drive synergistic discovery.”
Dr. Ma’ayan and Joel Dudley, PhD, Assistant Professor of Genetics and Genomic Sciences, and Director of Biomedical Informatics at the Icahn School of Medicine at Mount Sinai, received a separate grant of $1.2 million from the NIH to spur drug discovery. They will build The Knowledge Management Center for Illuminating the Druggable Genome that assembles, organizes, and visualizes data collected from protein kinases, nuclear receptors, ion channels, and G-protein-coupled receptors.