About Josh Tycko

Department of Neurobiology

Harvard Medical School

I develop high-throughput synthetic biology technologies to manipulate and measure human gene regulation.

I am currently a postdoctoral fellow at Harvard Medical School and BIDMC working in the labs of Michael Greenberg and Martin Pollak.

I completed my Ph.D. at Stanford University in the labs of Michael Bassik and Lacra Bintu with support from the NIH F99/K00 Fellowship and NSF GRFP. At Stanford, I was a teaching assistant for a course on the science and bioethics of CRISPR, was an instructor for a hands-on cell engineering lab, and mentor to our amazing iGEM team. As a BioFutures Fellow and co-leader of The Genetics Advocacy Committee, I collaborated with fellow trainees to critically analyze and improve graduate STEM training.

Research

Gene and chromatin regulation

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.

Gene delivery

We identified novel recombinases from bacteriophages that can integrate large DNA sequences into the human genome. Previously, we used AAV vectors to deliver antibody genes as a way to prevent RSV infection.

Genetic and epigenetic editing

We built and used CRISPR tools to functionally investigate the non-coding genome. We also developed new biochemical, cellular, and computational approaches to measure, model, and mitigate CRISPR off-target effects to make safer therapies.

Selected Research Articles

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

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, Michael Bassik

Nature Biotechnology, 2024

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

Systematic discovery of recombinases for efficient integration of large DNA sequences into the human genome.

Matthew Durrant*, Alison Fanton*, Josh Tycko*, Michaela Hinks, Sita Chandrasekaran, Nicholas T Perry, Julia M. Schaepe, Peter P. Du, Peter Lotfy, Michael Bassik, Lacramioara Bintu, Ami Bhatt, Patrick Hsu

Nature Biotechnology, 2022

Adeno-Associated Virus Vector-Mediated Expression of Antirespiratory Syncytial Virus Antibody Prevents Infection in Mouse Airways

Josh Tycko, V. Adam, M. Crosariol, J. Ohlstein, Julio Sanmiguel, A. Tretiakova, Soumitra Roy, S. Worgall, James M. Wilson, M. Limberis

Human Gene Therapy, 2021

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

Pairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells

Josh Tycko, Luis A. Barrera, Nicholas C. Huston, Ari E. Friedland, Xuebing Wu, J. Gootenberg, O. Abudayyeh, V. Myer, Christopher J. Wilson, P. Hsu

Nature Communications, 2018

Additional Research Articles

Toward optimizing diversifying base editors for high-throughput mutational scanning studies

Carley I Schwartz, Nathan S Abell, Amy Li, Aradhana, Josh Tycko, Alisa Truong, Stephen B. Montgomery, Gaelen T. Hess

Nucleic Acids Research, 2025

Cytotoxicity of activator expression in CRISPR-based transcriptional activation systems

Ziyan Liang, Aakaanksha Maddineni, Jesus A. Ortega, Christine B Magdongon, Shreya Jambardi, Subrata Roy, Josh Tycko, Ajinkya Patil, Mark Manzano, Elizabeth T. Bartom, Eva Gottwein

Nature Communications, 2025

Tunable, self-contained gene dosage control via proteolytic cleavage of CRISPR-Cas systems

Noa Katz, Connie An, Yu-Ju Lee, Josh Tycko, Meng Zhang, Jeewoo Kang, Lacramiora Bintu, Mike C Bassik, Wei-Hsiang Huang, Xiaojing J. Gao

bioRxiv, 2024

Prediction and design of transcriptional repressor domains with large-scale mutational scans and deep learning

Raeline Valbuena*, AkshatKumar Nigam*, Josh Tycko, Peter Suzuki, Kaitlyn Spees, Aradhana, Sophia Arana, Peter Du, Roshni A. Patel, Lacramiora Bintu, Anshul Kundaje, Michael Bassik

bioRxiv, 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, Michael 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

CasKAS: direct profiling of genome-wide dCas9 and Cas9 specificity using ssDNA mapping

G. Marinov, Samuel H. Kim, S. Bagdatli, Soon Il Higashino, Alexandro E. Trevino, Josh Tycko, Tong Wu, Lacramioara Bintu, M. Bassik, Chuan He, A. Kundaje, W.J. Greenleaf

Genome Biology, 2023

A genome-wide genetic screen uncovers determinants of human pigmentation

V. Bajpai, T. Swigut, Jaaved Mohammed, S. Naqvi, M. Arreola, Josh Tycko, Tayne C. Kim, J. Pritchard, M. Bassik, Joanna Wysocka

Science, 2023

Modeling the efficacy of CRISPR gene drive for snail immunity on schistosomiasis control

R. Grewelle, J. Perez-Saez, Josh Tycko, E. Namigai, Chloe Rickards, G. D. De Leo

PLoS Neglected Tropical Diseases, 2022

Identification of Guide-Intrinsic Determinants of Cas9 Specificity

Nicholas C. Huston, Josh Tycko, Eric L Tillotson, Christopher J. Wilson, V. Myer, H. Jayaram, Barrett E Steinberg

The CRISPR Journal, 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

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

Reviews

Deciphering the impact of genomic variation on function.

The ENCODE4 Consortium

Nature, 2024

The sound of silence: Transgene silencing in mammalian cell engineering.

A Cabera*, HI Edelstein*, F Glykofrydis*, KS Love*, S Palacios*, J Tycko*, M Zhang*, S Lensch, CE Shields, M Livingston, R Weiss, H Zhao, K Haynes, L Morsut, YY Chen, AS Khalil, W Wong, J Collins, S Rosser, K Polizzi, M Elowitz, M Fussenegger, IB Hilton, JN Leonard, L Bintu, KE Galloway, TL Deans

Cell Systems, 2022

Gene drives for schistosomiasis transmission control

T. Maier, Nicolas J. Wheeler, E. Namigai, Josh Tycko, R. Grewelle, Y. Woldeamanuel, Katharina Klohe, J. Perez-Saez, S. Sokolow, G. D. De Leo, T. Yoshino, M. Zamanian, J. Reinhard-Rupp

PLoS Neglected Tropical Diseases, 2019

Methods and Applications of CRISPR-Mediated Base Editing in Eukaryotic Genomes.

Gaelen T. Hess*, Josh Tycko*, David Yao*, M. Bassik

Molecular Cell, 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

Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity.

Josh Tycko, Vic Myer, Patrick Hsu

Molecular Cell, 2016

Lessons learned from the clinical development and market authorization of Glybera.

L. Bryant*, Devin M. Christopher*, April R. Giles*, Christian J. Hinderer*, Jesse Rodriguez*, J. Smith*, Elizabeth A. Traxler*, Josh Tycko*, Adam P. Wojno*, James M. Wilson

Human Gene Therapy Clinical Development, 2013

Patents, Posters, and Other

P. Hsu, Morgan L. Maeder, P. Odonnell, Josh Tycko, Nicholas C. Huston

2017

317. Screening S. Aureus CRISPR-Cas9 Paired-Guide RNAs for Efficient Targeted Deletion in Duchenne Muscular Dystrophy

Josh Tycko, Nicholas C. Huston, J. Robinson-Hamm, Christopher J. Wilson, C. Gersbach, P. Hsu, D. Bumcrot

2016