Brian D. Gregory

Associate Professor of Biology
103D Carolyn Lynch Laboratory
bdgregor@sas.upenn.edu
215-746-4398
Plant Biology
Genetics, Epigenetics, Genomics
Computational Biology
Education: 

Ph.D., Harvard University, 2005

B.S.A., Univeristy of Arizona, 2000

Research Interests: 

Using high-throughput sequencing to study RNA secondary structure and RNA-protein interactions globally

We have pioneered the development of high-throughput, sequencing-based approaches to simultaneously study RNA secondary structure and RNA-protein interactions on a global scale. To do this, we have married classical nuclease-based structure mapping techniques with high-throughput sequencing technology to interrogate the protein binding profile and pairing status of all nucleotides in the RNA molecules of eukaryotic organisms. We believe that the findings from these approaches highlight the importance of RNA-protein interactions and RNA secondary structure in eukaryotes and present an approach that should be widely applicable for the analysis of these key features in any and all organisms.

We are also using these approaches to identify all small (sm)RNA-producing substrates of RNA-DEPENDENT RNA POLYMERASEs (RDRs). More specifically, we use the combination of transcriptome-wide double-stranded (dsRNA) and small RNA sequencing to interrogate the substrates of this class of enzymes in eukaryotes. We are currently characterizing the RDRs of Arabidopsis thaliana.

Mechanisms and regulation of RNA silencing pathways

Making use of genomic, bioinformatic, and systems biology approaches with molecular genetic and biochemical techniques we are identifying and characterizing additional components required for the metabolism of various classes of smRNAs, as well as proteins involved in the regulation of specific smRNA populations and RNA silencing pathways. Specifically, our lab is taking a genetic approach using the model genetic organismArabidopsis thaliana to identify new factors, and have already identified candidate genes that we are characterizing using genomic, molecular biological, and cell biological techniques in Arabidopsis. Furthermore, as these pathways are highly conserved, we are also studying these factors in smRNA pathways in animal models. The findings from this work will allow a better understanding of how RNA silencing pathways function, and the ways they can be manipulated for controlling gene expression across eukaryotic systems.

Selected Publications: 

Foley, S.W., Gosai, S.J., Wang, D., Selamoglu, N., Solitti, A.C., Koster, T., Steffen, A., Lyons, E., Daldal, F., Garcia, B.A., Staiger, D., Deal, R.B., and Gregory, B.D. 2017. A global view of RNA-protein interactions identifies post-transcriptional regulators of root hair cell fate. Dev. Cell 41: 204-220.

Yu, X., Willmann, M.R., Anderson, S.J., and Gregory, B.D. 2016. Genome-wide mapping of uncapped and cleaved transcripts reveals a role for the nuclear messenger RNA cap-binding complex in plant co-translational RNA decay. Plant Cell 28: 2385-2397.

Vandivier, L.E., Anderson, S.J., Foley, S.W., and Gregory B.D. 2016. The conservation and function of RNAsecondary structure in plants. Annu. Rev. Plant Biol. 67: 463-488.

Berkowitz, N.D., Silverman, I.M., Childress, D.M., Wang, L.S., and Gregory, B.D. 2016. A comprehensive database of high-throughout sequencing-based RNA secondary structure probing data (Structure Surfer). BMC Bioinformatics 17: 215.

Vandivier, L.E., Campos, R., Kuksa, P.P., Silverman, I.M., Wang, L.S., and Gregory B.D. 2015. Chemical modifications mark alternatively spliced and uncapped messenger RNAs in Arabidopsis. Plant Cell 27: 3024-3037.

Foley, S.W., Vandivier, L.E., Kuksa, P.P., and Gregory, B.D. 2015. Transcriptome-wide measurement of plant RNA secondary structure. Curr. Opin. Plant Biol. 27: 36-43.

Gosai, S.J., Foley, S.W., Wang, D., Silverman, I.M., Selamoglu, N., Nelson, A.D.L., Beilstein, M.A., Daldal, F., Deal, R.B., and Gregory, B.D. 2015. Global analysis of the RNA-protein interaction and RNA secondary structure landscapes of the Arabidopsis nucleus. Mol. Cell 57: 376-388.

Silverman, I.M., Li, F., Alexander, A., Goff, L., Trapnell, C., Rinn, J.L., and Gregory, B.D. 2014. RNase-mediated protein footprint sequencing reveals protein-binding sites throughout the human transcriptome. Genome Biol. 15: R3.

Li, F., Zheng, Q., Ryvkin, P., Dragomir, I., Desai, Y., Aiyer, S., Valladares, O., Yang, J., Bambina, S., Sabin, L.R., Murray, J.I., Lamitina, T., Raj, A., Cherry, S., Wang, L.S., and Gregory, B.D. 2012. Global analysis of RNA secondary structure in two metazoans. Cell Rep. 1: 69-82.

Courses Taught: 

BIOL 431: Genome Sciences and Genomic Medicine

BIOL 485: The RNA World