The LSP is an NIH National Center for Systems Biology and an NIH LINCS Project Data and Signature Generation Center. An overview of additional government-funded LSP research projects is provided below. LSP Investigators are also involved in collaborations with industry partners that apply a combination of multiplex measurement and computational modeling to understand mechanisms of drug action.
The HMS Laboratory of Systems Pharmacology – LSP (GM107618)
The Harvard Medical School (HMS) Laboratory of Systems Pharmacology (LSP) is a NIGMS Center for Systems Biology multi-disciplinary effort within HiTS to reinvent the fundamental science underlying the development of new medicines and their use in individual patients.
Every cell is an extensively interconnected ecosystem. Any given gene may influence dozens or hundreds of other genes. Systems Pharmacology investigates drug action at the level of entire biochemical and genetic networks, rather than looking at the effect of any single element. The LSP brings together investigators in mathematical and experimental disciplines from multiple academic institutions (Harvard, MIT, Tufts) and research hospitals (Dana Farber, MGH, BWH) and eventually visiting scientists from the FDA and local drug companies to integrate computational and systems approaches into all phases of drug discovery and development.
Pharmaco-Response Signatures & Disease Mechanism – The HMS LINCS Center (HL127365)
The Harvard Medical School Library of Integrated Network-based Cellular Signatures (LINCS) Center was established in October 2010 to create libraries of measurable cellular responses or signatures that describe how cells respond to perturbation. As of March 2017, six centers across the U.S. participate in the NIH LINCS program. The aim of the HMS LINCS Center is to create signatures that measure the responses of cells derived from different human tissues to therapeutic drugs. Much of the work focuses on tumor cells (from breast, liver and colon), but we also study primary human cells from normal and diseased patients. As perturbing agents, our focus is on small molecule kinase inhibitors, which are a leading class of therapeutic agents for treatment of cancer, autoimmune and other diseases.
The HMS Center for Cancer Systems Pharmacology – CCSP (CA225088)
The HMS Center for Cancer Systems Pharmacology (CCSP Center) is a NCI Cancer Systems Biology Consortium Center that constructs and applies network-level computational models to understand mechanisms of drug response, resistance and toxicity for targeted small molecule drugs and immune checkpoint inhibitors (ICIs). By systematically dissecting how resistance to targeted therapies and ICIs arises, we aim to understand and overcome resistance mechanisms using new drugs or drug combinations, while simultaneously predicting and balancing potential toxicities.
Communicating with Computers: Active Context (W911NF-15-1-0544)
The DARPA Communicating with Computers (CwC) program develops technologies for a new generation of human-machine interaction in which machines act as proactive collaborators rather than merely problem solving tools. We are developing an interactive dialogue system which allows scientists to interact with a computer partner – one that is able to harness knowledge extracted from the biomedical literature – to construct and test hypotheses about molecular systems. Listen to a podcast about our work, which appeared in The Guardian or check out the following article authored by the director of DARPA that appeared in WIRED.
World Modelers: Global Reading and Assembly for Semantic, Probabilistic World Models (W911NF-18-1-0014)
The DARPA World Modelers program aims to develop automated information collection and computational modeling techniques to understand the complex dynamics of global processes such as food security, migration and public health. We are developing the INDRA-GEM (Integrated Network and Dynamical Reasoning Assembler for Generalized Ensemble Modeling) automated model assembly system, which integrates information from diverse sources and implements novel probabilistic assembly techniques that can account for the uncertain nature of information in models.
An Automated Scientific Discovery Framework (ASDF) for Mechanistic Reasoning Across Complex Data (W911NF018-1-0124)
The DARPA Automated Scientific Discovery Framework program (ASDF) will develop algorithms and software for reasoning about complex mechanisms operating in the natural world, explaining large-scale data, assisting humans in generating actionable, model-based hypotheses and testing these hypotheses empirically.