Systems Pharmacology



Systems Pharmacology

We use the term "systems pharmacology" to define research that aims at understanding how drugs work (on specific pathways, on different cell types and in different tissues/organs/diseases), what the variability in patient response is and why many cancer treatments fail. Using a broad array of technologies including in vivo imaging of pharmacokinetics, intravital pharmacodynamic imaging (IPDI), mass spectrometry analysis, novel nanotechnology sensing approaches and chemical biology we obtain quantitative measurements and then develop mechanistic and probabilistic models. Network analysis and quantitative measurements of drug actions and side effects play a key component. Ultimately, we hope to improve our poor understanding of treatment response and define new targets drugs (or synergistic combinations) to tackle complex diseases.

Some of the Questions we are currently addressing are:

  • What are the molecular and cellular pathways from drug engaging target to tumor regression for any drug ?
  • What makes a cancer cell more, or less, responsive to drug X than a cell in the most relevant normal tissue (where toxicity occurs) ?
  • Why do some patients respond better than others? How can we predict the best drug/combination for a particular patient ?
  • How do cancers become drug resistant, and how can we combat this ?
  • What is the effect of cancer drugs on immune cells and can drug combinations be used to enhance anti-cancer efficacy ?
  • What are the most appropriate read-outs of drug efficacy and toxicity in clinical trials ?
  • How does taxol work on cancers if only < 5% of cancer cells are in M-phase in vivo ?

This Program is multidisciplinary and inter-institutional involving investigators from the Department of Systems Biology at Harvard Medical School (Initiative in Systems Pharmacology), Harvard affiliated teaching hospitals and MIT.

Recent Publications (more...)

Dubach JM, Kim E, Yang K, Cuccarese M, Giedt RJ, Meimetis LG, Vinegoni C, Weissleder R
Quantitating drug-target engagement in single cells in vitro and in vivo.
Nat Chem Biol. 2016;13(2):168-173 - PMID: 27918558
Vinegoni C, Fumene Feruglio P, Brand C, Lee S, Nibbs AE, Stapleton S, Shah S, Gryczynski I, Reiner T, Mazitschek R, Weissleder R
Measurement of drug-target engagement in live cells by two-photon fluorescence anisotropy imaging.
Nat Protoc. 2017;12(7):1472-1497 - PMID: 28686582

Recent News (more...)

2016-12-14: Sean Arlauckas, PhD of the Weissleder Lab received the honor of “Top Poster” at the 2nd Annual Symposium of the Harvard Program in Therapeutic Sciences. Congratulations, Sean!
2013-06-17: Harvard Medical School launches the Harvard Program in Therapeutic Science, to be known as HiTS, a collaborative endeavor with the ambitious goal of enhancing and eventually leading efforts to reinvent the ways in which we discover and evaluate therapeutic drugs and devices. HiTS will be headed by Peter Sorger, the Otto Krayer Professor in Systems Pharmacology at HMS.
2013-01-16: Reinventing the discovery and use of therapeutic drugs at the Lab of Systems Pharmacology, Harvard Medical School - a video describing how researchers use a network based approach to pharmacology, combining quantitative, multi-factorial measurement with diverse computational methods to study signalling pathways and their responses to drugs. publishes video describing
2012-01-06: Marc Kirschner, PhD, Chairman of Harvard Medical School’s Department of Systems Biology and a major CSB collaborator, outlines his vision for the Initiative in Systems Pharmacology (ISP) in Nature (pdf)
2011-10-18: CSB plays a major role in the newly launched Initiative in Systems Pharmacology at Harvard Medical School.