Paul A. Clemons
Genetic correlates of small-molecule sensitivity
Seashore-Ludlow B, Rees MG, Cheah JH, et al. Harnessing connectivity in a large-scale small-molecule sensitivity dataset. Cancer Discov. 2015 Nov;5(11):1210-1223. Epub 2015 Oct 19.
Public small-molecule activity databases
Howe EA, de Souza A, Lahr DL, et al. BioAssay Research Database (BARD): chemical biology and probe-development enabled by structured metadata and result types. Nucleic Acids Res. 2015 Jan;43(Database issue):D1163-D1170. Epub 2014 Dec 4.
Performance analysis of screening collections
Wawer MJ, Li K, Gustafsdottir SM, Ljosa V, et al. Toward performance-diverse small-molecule libraries for cell-based phenotypic screening using multiplexed high-dimensional profiling. Proc Natl Acad Sci U S A. 2014;111(30):10911-10916. Epub 2014 Jul 14.
Profile-based structure-activity relationships
Wawer MJ, Jaramillo DE, Dančík V, et al. Automated structure-activity relationship mining: connecting chemical structure to biological profiles. J Biomol Screen. 2014;19(5):738-748.
Connectivity approaches to mechanism of action
Dančík V, Carrel H, Bodycombe NE, et al. Connecting small molecules with similar assay performance profiles leads to new biological hypotheses. J Biomol Screen. 2014;19(5):771-781.
Paul A. Clemons, Ph.D.
Paul Clemons is an institute scientist and the director of computational chemical biology research in the Chemical Biology and Therapeutics Science Program at the Broad Institute of MIT and Harvard. Clemons and his team use quantitative measurement, computational, and visualization techniques to enable systematic use of small molecules to explore biology, especially disease biology.
In collaboration with biologists, Clemons works to understand the consequences of small-molecule action on cells, particularly using multiple readouts, such as gene-expression profiles or profiles based on cellular imaging. Working with chemists, Clemons helps to identify the consequences of synthetic chemistry decisions on small-molecule performance, with the goal of developing prolific and performance-diverse small-molecule screening collections optimized for probe-discovery projects.
The Clemons group’s current research activities include quantifying similarity and diversity (including performance diversity) of small-molecule collections, using small molecules to modulate cellular processes, and multidimensional analysis of datasets from high-throughput biological testing. Of particular interest are relationships of chemical structure to small-molecule performance, especially in cells, and understanding the genetic bases of small-molecule sensitivity and responses in cells.
Prior to joining the Broad Institute in 2005, Clemons was an institute fellow at the Harvard Institute of Chemistry & Cell Biology (ICCB), where he led technology development projects and conducted basic research to bring computational approaches to chemical-genetics research. In the context of the National Cancer Institute’s Initiative for Chemical Genetics (first at ICCB and later at Broad) and the Molecular Libraries Probe-production Centers Network, the Clemons group helped develop tools such as ChemBank and BioAssay Research Database (BARD): public, small-molecule structure and data-analysis environments that life scientists can use. More recently, the Clemons group has participated in development of the Cancer Therapeutics Response Portal (CTRP) and NCI CTD2 Dashboard.
Clemons holds a B.S. in biochemical and biophysical sciences from the University of Houston and a Ph.D. in biochemistry from Harvard University’s molecular and cellular biology department. As a graduate student, Clemons was a lead investigator in a large team effort to develop a “one-bead, one-stock solution” approach to chemical genetics, a precursor to the chemistry technology platform still in use by the Broad Institute.