Josh Tycko

Systematic discovery of protein functions in human cells to understand gene regulation and enable genetic medicine

Gene and chromatin regulation


We developed HT-recruit to systematically discover and characterize transcriptional effector domains in human cells. We discovered transcriptional effector domains in 600 human proteins and shed new light on the evolution of major transcription factor families, like KRAB and Hox, while also engineering improved activator and repressor domains for synthetic biology.


Publications


Multicenter integrated analysis of noncoding CRISPRi screens


David Yao*, Josh Tycko*#, Jin Woo Oh*, Lexi R. Bounds*, Sager J. Gosai*, Lazaros Lataniotis*, Ava Mackay-Smith, Benjamin R. Doughty, I. Gabdank, Henri Schmidt, Tania Guerrero-Altamirano, Keith Siklenka, Katherine Guo, Alexander D White, Ingrid Youngworth, Kalina Andreeva, Xingjie Ren, Alejandro Barrera, Yunhai Luo, G. Yardımcı, R. Tewhey, A. Kundaje, William J. Greenleaf, P. Sabeti, Christina S. Leslie, Y. Pritykin, Jill E. Moore, Michael A Beer, C. Gersbach, Timothy E. Reddy, Yin Shen, Jesse M Engreitz, M. Bassik, Steven K. Reilly#

Nature Methods, 2024


High-throughput functional characterization of combinations of transcriptional activators and repressors


Aditya Mukund, Josh Tycko, S. J. Allen, S. A. Robinson, Cecelia Andrews, Joydeb Sinha, Connor H. Ludwig, Kaitlyn K. Spees, M. Bassik, Lacramioara Bintu

Cell Systems, 2023


High-Throughput Discovery and Characterization of Viral Transcriptional Effectors in Human Cells


Connor H. Ludwig, A. Thurm, D. Morgens, Kevin Yang, Josh Tycko, M. Bassik, B. Glaunsinger, Lacramioara Bintu

Cell Systems, 2023


Development of compact transcriptional effectors using high-throughput measurements in diverse contexts


Josh Tycko, Mike V. Van, Aradhana, Nicole DelRosso, David Yao, Xiaoshu Xu, Connor Ludwig, Kaitlyn K. Spees, Kathy Liu, Gaelen T. Hess, Mingxin Gu, Aditya Mukund, Peter H. Suzuki, Roarke A. Kamber, Lei S. Qi, Lacramioara Bintu, M. Bassik

bioRxiv, 2023


Large-scale mapping and mutagenesis of human transcriptional effector domains


Nicole DelRosso, Josh Tycko, Peter H. Suzuki, Cecelia Andrews, Aradhana, Aditya Mukund, Ivan Liongson, Connor Ludwig, Kaitlyn K. Spees, P. Fordyce, M. Bassik, Lacramioara Bintu

Nature, 2023


High-Throughput Discovery and Characterization of Human Transcriptional Effectors


Josh Tycko, Nicole DelRosso, Gaelen T. Hess, Aradhana, A. Banerjee, Aditya Mukund, Mike V. Van, Braeden K. Ego, David Yao, Kaitlyn K. Spees, Peter H. Suzuki, G. Marinov, A. Kundaje, M. Bassik#, Lacramioara Bintu#

Cell, 2020


Mitigation of off-target toxicity in CRISPR-Cas9 screens for essential non-coding elements


Josh Tycko*, M. Wainberg*, G. Marinov*, Oana Ursu, Gaelen T. Hess, Braeden K. Ego, Aradhana, Amy Li, Alisa N Truong, Alexandro E. Trevino, Kaitlyn K. Spees, David Yao, Irene M. Kaplow, P. Greenside, D. Morgens, D. Phanstiel, M. Snyder, Lacramioara Bintu, W. Greenleaf, A. Kundaje, M. Bassik

Nature Communications, 2019


Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements


Maxwell R. Mumbach, Ansuman T. Satpathy, E. Boyle, Chao Dai, Benjamin G. Gowen, S. Cho, M. Nguyen, Adam J. Rubin, Jeffrey M Granja, Katelynn R. Kazane, Yuning Wei, Trieu Nguyen, P. Greenside, M. Corces, Josh Tycko, Dimitre R. Simeonov, Nabeela Suliman, Rui Li, Jin Xu, Ryan A. Flynn, A. Kundaje, P. Khavari, A. Marson, J. Corn, T. Quertermous, W. Greenleaf, Howard Y. Chang

Nature Genetics, 2017


Advancing towards a global mammalian gene regulation model through single-cell analysis and synthetic biology


Josh Tycko*, Mike V. Van*, Michael B. Elowitz, Lacramioara Bintu

Current Opinion in Biomedical Engineering, vol. 4, 2017 Oct 30, pp. 174-193


Toolbox for Exploring Modular Gene Regulation in Synthetic Biology Training.


Michael S. Magaraci, Jessica G Bermudez, Deeksha Yogish, D. H. Pak, Viktor Mollov, Josh Tycko, D. Issadore, Sevile G. Mannickarottu, B. Chow

ACS synthetic biology, 2016




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