Dr. Gaelen Hess is an Assistant Professor within the Department of Biomolecular Chemistry and Center for Human Genomics and Precision Medicine.
With the emerging appreciation of precision medicine, the link of genetic and epigenetic perturbations to their phenotypes is vital. With the advent of CRISPR-mediated genome editing and high-throughput sequencing, we can both systematically perturb the genome and quantitatively measure their phenotypic effects. In the Hess lab, we are interested in both the development and application of these and other functional genomics technologies to address critical biological questions and improve human health. Using these cutting-edge genomics tools, we focus on three areas: (1) investigating mechanisms of drug resistance and response, (2) regulation of mammalian DNA repair, and (3) studying effectors secreted by bacterial pathogens.
- Tycko J, DelRosso N, Hess GT, Aradhana, Banerjee A, Mukund A, Van MV, Ego BK, Yao D, Spees K, Suzuki P, Marinov GK, Kundaje A, Bassik MC, Bintu L. High-throughput discovery and characterization of human transcriptional effectors. Cell 183: 2020-2035.e16 (2020).
- Morgens DW, Chan C, Kane AJ, Weir NR, Li A, Dubreuil MM, Tsui CK, Hess GT, Lavertu A, Han K, Polyakov N, Handy EL, Alabi P, Dombroski A, Yao D, Altman RB, Sello JK, Denic V, and Bassik MC. Retro-2 protects cells from ricin toxicity by inhibiting ASNA1-mediated ER targeting and insertion of tail-anchored proteins. eLife. 8: e48434 (2019).
- Tycko J, Wainberg M, Marinov GK, Ursu O, Hess GT, Ego BK, Aradhana, Li A, Truong A, Trevino AE, Spees K, Yao D, Kaplow IM, Greenside PG, Morgens DW, Phanstiel DH, Snyder MP, Bintu L, Greenleaf WJ, Kundaje A, and Bassik MC. Mitigation of off-target toxicity in CRISPR-Cas9screens for essential non-coding elements. Nature Communications. 10: 1-14 (2019).
- Hess, GT, Tycko J, Yao D, and Bassik MC. Methods and applications of CRISPR-mediated base editing in eukaryotic genomes. Molecular Cell. 68: 26-43 (2017).
- Morgens DW*, Wainberg M*, Boyle EA, Ursu O, Araya CL, Tsui K, Haney MS, Hess GT, Han K, Jeng EE, Li A, Snyder MP, Greenleaf WJ, Kundaje A, and Bassik MC. Off-target behavior of truncated guides in genome-wide CRISPR/Cas9 screens. Nature Communications. 8: 1-8 (2017).
- Han K*, Jeng EE*, Hess GT, Morgens DW, Li A, and Bassik MC. Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature Biotechnology. 35: 463-474 (2017).
- Hess GT, Fresard L, Han K, Lee CH, Li A, Cimprich KA, Montgomery SB, and Bassik, MC. Directed evolution using dCas9-targeted somatic hypermutation machinery. Nature Methods. 13: 1036-1042 (2016).
- Hess GT, Guimaraes CP, Spooner E, Ploegh HL, and Belcher AM. Orthogonal labeling of M13 minor capsid proteins with DNA to self-assemble end-to-end multiphage structures. ACS Nano. 2: 490-496 (2013).
- Hess GT, Cragnolini JJ, Popp MW, Allen MA, Dougan SK, Spooner E, Ploegh HL, Belcher AM, Guimaraes CP. M13 bacteriophage display framework that allows sortase-mediated modification of surface-accessible phage proteins. Bioconjugate Chemistry. 23: 1478-87 (2012).