Todd Golub - L1000 transcriptional profiling
I have been working with Aravind Subramanian and Todd Golub since the beginning of LINCS in 2010. We are combing the L1000 transcriptional profiling of the Broad LINCS U54 center with the phenotypic and biochemical profiling done by the HMS U54 LINCS center. We are analyzing six cell lines treated with hundreds of kinase inhibitors and dozens of soluble growth factors. Working with Marc Hafner, a post doc in Peter Sorger's group, I am attempting to identify cell type specific differences in the response to perturbation and to understand synergy between different drugs.
Nathanael S. Gray - Small molecule inhibitors
Nathanael Gray and his lab have been instrumental in assembling the LINCS kinase inhibitor library. I used this collection of about 300 therapeutic drugs and tool compounds to treat six breast cancer cell lines to create both transcriptional and phenotypic response profiles. In addition, with members of the Gray lab I have explored the specificity and off-target binding effects of kinase inhibitors. We are further developing this work by creating a reliable mass spec assay to measure target engagement of kinase inhibitors and by created a searchable database of kinase inhibitors and their targets.
Steve P. Gygi - Mass spectroscopy profiling of breast cancer cell lines
The Gygi lab has been leading the way in developing new and improved ways of cellular profiling. I have worked with multiple post-docs to profile the kinome and cell surface proteome in cell lines. In addition, we are improving methods to probe the targets of kinase inhibitors and to absolutely quantify components of signaling pathways.
Avi Ma'ayan - Analyzing L1000 transcriptional profiling data
Members in the Ma'ayan lab helped to visualize our L1000 profiling data and improve the methods used to cluster the results. We are working together to try and transfer results from our limited exploration of six cell lines to the totality of CMAP results.
Joshua Stuart - Combining proteomic and genomic profiling data
Both genomic and proteomic profiling of cells leads to a bewildering array of complex data that can not be interpreted by inspection alone. The expertise of Josh's lab is helping us to make sense of our profiling data. But combining multiple sources of profiling data we are hoping to understand the interplay between mutation and copy number variation, transcriptional profiles, protein measurements, and pathway activity. Our ultimate goal is to use these combined data to explain cell lines specific drug responses.
Steven H. Wiley - Mass spectrometry of the MAPK signaling pathway
Steven Wiley and I started working together since 2009 with the goal to directly measure protein components of signaling pathways to parameterize ODE models. After a significant amount of method development we are now able to quantify a number of rare components of the MAPK signaling pathway. We are now exploring if the expression of a subset of these proteins explains cell type specific signaling responses.