doi.bio/patrick_d_hsu

Patrick D. Hsu

Patrick D. Hsu is an Assistant Professor and Deb Faculty Fellow at the University of California, Berkeley. He is also a Core Investigator and Co-Founder of the Arc Institute. Hsu received his A.M. and Ph.D. from Harvard University and is a pioneer in the field of CRISPR gene editing.

Research Focus

Hsu's research group works at the intersection of biology, bioengineering, engineering, and AI to develop new molecular technologies for genome and transcriptome engineering. They aim to understand and manipulate the genetic circuits that control brain and immune cell function for the next generation of gene and cell therapies.

Awards

• NIH Early Independence Award
• MIT Technology Review's Innovators Under 35
• Berkeley Engineering's Deb Faculty Fellowship
• Rainwater Prize for Innovative Early-Career Scientists
• Amgen Young Investigator Award

Notable Publications

• A Nature Biomedical Engineering cover paper on the development of an extraction-free, attomolar-sensitivity CRISPR diagnostic test integrated into a microfluidic cartridge and real-time detection device.
• A Nature Chemical Biology cover paper, in collaboration with the Doudna and Savage labs, on dual CRISPR nucleases for rapid and sensitive one-pot CRISPR diagnostics.
• A Nature Biotechnology paper on the serine recombinase study for gene writing.
• A Nature Genetics paper on a genome-wide search for COVID host factors, in collaboration with the Konermann lab at Stanford and the Harris lab at UC Berkeley.

Patrick D. Hsu

Overview

Patrick D. Hsu is a researcher and academic with a focus on CRISPR gene editing, synthetic biology, bioengineering, and genomics. He works at the intersection of biology and AI to develop new biotechnologies and improve human health. Hsu is currently an Assistant Professor and Deb Faculty Fellow at the University of California, Berkeley, and a co-founder and core investigator at the Arc Institute.

Education

Hsu received his A.M. and Ph.D. degrees from Harvard University, where he focused on CRISPR/Cas9 genome engineering technologies and transcriptional/epigenetic regulation of memory and neurodegeneration. He also holds a Bachelor of Science degree in Chemistry and Physics from the California Institute of Technology.

Career

Hsu has previously held positions at the Broad Institute of MIT and Harvard, the McGovern Institute for Brain Research at MIT, Editas Medicine, and the Salk Institute. He has been recognized by Forbes' 30 Under 30, the NIH Early Independence Award, the MIT Technology Review's Innovators Under 35, and the Rainwater Prize for Innovative Early-Career Scientists, among other awards.

Notable Works

• Sequence modeling and design from molecular to genome scale with Evo: In this work, Hsu and his team developed Evo, a genomic foundation model that enables prediction and generation tasks from the molecular to the genome scale. Evo was trained on whole prokaryotic genomes and can generalize across the three fundamental modalities of the central dogma of molecular biology. It can be used for zero-shot function prediction and multielement generation tasks, such as generating synthetic CRISPR-Cas molecular complexes.
• Rewriting endogenous human transcripts with trans-splicing: This study introduced RESPLICE, a new mode of RNA editing that uses RNA-guided trans-splicing with a Cas editor to enable fine-tuned and transient control of cellular programs without permanent alterations to the genetic code.
• Bridge RNAs direct modular and programmable recombination of target and donor DNA: The paper reports on the discovery of IS110 insertion sequences, a family of minimal and autonomous mobile genetic elements, and their potential for genomic rearrangements. The IS110 bridge system expands the diversity of nucleic acid-guided systems and offers a unified mechanism for fundamental DNA rearrangements required for genome design.
• Deep learning and CRISPR-Cas13d ortholog discovery for optimized RNA targeting: This work focuses on optimizing RNA targeting by evaluating seven machine learning models to build a guide efficiency prediction algorithm orthogonally validated across multiple human cell types.
• The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses: The study identifies the KDM6A/KMT2D/EP300 axis as a potential drug target for diverse coronaviruses, including SARS-CoV, SARS-CoV-2, and MERS-CoV. It highlights the role of this axis in promoting viral entry by regulating the expression of multiple coronavirus receptors.
• DYRK1A promotes viral entry of highly pathogenic human coronaviruses: This paper identifies DYRK1A as a novel regulator of ACE2 and DPP4 expression, which may dictate susceptibility to multiple highly pathogenic human coronaviruses. The study demonstrates that DYRK1A regulates ACE2 and DPP4 transcription independent of its catalytic kinase function.

Research Interests

• Molecular Technologies: Inventing molecular tools for biological programming by leveraging microbial bioinformatics, functional biochemical and molecular assays, and protein engineering.
• Merging Biology and AI: Developing biological foundation models for generative DNA and protein design, and virtual cell models for predicting cellular responses.

- Human Synthetic Biology: Pushing the boundaries of synthetic biology in human cells via genome, epigenome, transcriptome, and protein engineering to address unmet therapeutic needs.

Patrick D. Hsu

Early Life and Education

Patrick D. Hsu is a researcher and academic in the fields of biochemistry, genomics, and AI. He received his A.M. and Ph.D. degrees from Harvard University, where he was a James Mills Pierce Fellow and a Harvard Merit Fellow.

Career

Hsu is currently an Assistant Professor and Deb Faculty Fellow at the University of California, Berkeley, and a co-founder and core investigator at the Arc Institute. He is also an investigator at the Innovative Genomics Institute (IGI), a joint research collaboration between Berkeley and UCSF. Previously, he was a Principal Investigator and Salk Faculty Fellow at the Salk Institute from 2015-2019.

Hsu's research focuses on biological programming, LLMs for biology, genome mining and editing, and functional genomics. He works at the intersection of biology and AI, developing new biotechnologies, biological foundation models, and therapies. His lab integrates synthetic biology, bioengineering, and genomics to develop molecular technologies for genome and transcriptome engineering.

Hsu has made significant contributions to the early development of CRISPR-Cas9 technologies for human genome engineering, and his lab recently discovered and developed novel CRISPR systems that expand gene editing capabilities beyond DNA to RNA. He has also worked on CRISPR diagnostics and the application of CRISPR technologies to COVID-19 research, including antibody tests, diagnostic tests, and understanding host factors and mechanisms of infection.

Awards and Recognition

Hsu's work has been recognized through numerous awards, including:

• NIH Early Independence Award
• MIT Technology Review's Innovators Under 35
• Rainwater Prize for Innovative Early Career Scientists
• Amgen Young Investigator Award
• Forbes 30 Under 30
• Rose Hills Innovator

Google Scholar

Patrick D. Hsu

University of California, Berkeley

http://hsu.berkeley.edu/

Multiplex genome engineering using CRISPR/Cas systems L Cong, FA Ran, D Cox, S Lin, R Barretto, N Habib, PD Hsu, X Wu, … Science 339 (6121), 819-823, 2013 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:d1gkVwhDpl0C

Genome engineering using the CRISPR-Cas9 system F Ran, PD Hsu, J Wright, V Agarwala, DA Scott, F Zhang Nature protocols 8 (11), 2281-2308, 2013 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:zYLM7Y9cAGgC

Development and applications of CRISPR-Cas9 for genome engineering PD Hsu, ES Lander, F Zhang Cell 157 (6), 1262-1278, 2014 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:eQOLeE2rZwMC

DNA targeting specificity of RNA-guided Cas9 nucleases PD Hsu, DA Scott, JA Weinstein, FA Ran, S Konermann, V Agarwala, Y Li, … Nature biotechnology 31 (9), 827-832, 2013 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:2osOgNQ5qMEC

Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity FA Ran, PD Hsu, CY Lin, JS Gootenberg, S Konermann, AE Trevino, … Cell 154 (6), 1380-1389, 2013 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:IjCSPb-OGe4C

Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex S Konermann, MD Brigham, AE Trevino, J Joung, OO Abudayyeh, … Nature 517 (7536), 583-588, 2015 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:MXK_kJrjxJIC

Crystal structure of Cas9 in complex with guide RNA and target DNA H Nishimasu, FA Ran, PD Hsu, S Konermann, SI Shehata, N Dohmae, … Cell 156 (5), 935-949, 2014 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:Tyk-4Ss8FVUC

Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells X Wu, DA Scott, AJ Kriz, AC Chiu, PD Hsu, DB Dadon, AW Cheng, … Nature biotechnology 32 (7), 670-676, 2014 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:YsMSGLbcyi4C

Optical control of mammalian endogenous transcription and epigenetic states S Konermann, MD Brigham, AE Trevino, PD Hsu, M Heidenreich, L Cong, … Nature 500 (7463), 472-476, 2013 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:UeHWp8X0CEIC

Transcriptome engineering with RNA-targeting type VI-D CRISPR effectors S Konermann, P Lotfy, NJ Brideau, J Oki, MN Shokhirev, PD Hsu Cell 173 (3), 665-676. e14, 2018 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:e5wmG9Sq2KIC

Engineering of systems, methods and optimized guide compositions for sequence manipulation F Zhang, L Cong, P Hsu, RAN Fei US Patent 8,906,616, 2014 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:dshw04ExmUIC

Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus W Yang, N Shen, DQ Ye, Q Liu, Y Zhang, XX Qian, N Hirankarn, D Ying, … PLoS genetics 6 (2), e1000841, 2010 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:-f6ydRqryjwC

Structure and engineering of Francisella novicida Cas9 H Hirano, JS Gootenberg, T Horii, OO Abudayyeh, M Kimura, PD Hsu, … Cell 164 (5), 950-961, 2016 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:aqlVkmm33-oC

Methods for optimizing CRISPR-Cas9 genome editing specificity J Tycko, VE Myer, PD Hsu Molecular cell 63 (3), 355-370, 2016 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:dhFuZR0502QC

Crispr-cas component systems, methods and compositions for sequence manipulation F Zhang, L Cong, DBT Cox, P Hsu, LIN Shuailiang, RAN Fei, RJ Platt, … US Patent App. 14/105,035, 2014 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:4JMBOYKVnBMC

Test performance evaluation of SARS-CoV-2 serological assays JD Whitman, J Hiatt, CT Mowery, BR Shy, R Yu, TN Yamamoto, U Rathore, … Nature biotechnology 38 (10), 1174, 2020 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:D_sINldO8mEC

Evaluation of SARS-CoV-2 serology assays reveals a range of test performance JD Whitman, J Hiatt, CT Mowery, BR Shy, R Yu, TN Yamamoto, U Rathore, … Nature biotechnology 38 (10), 1174-1183, 2020 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:pyW8ca7W8N0C

Delivery and specificity of CRISPR/Cas9 genome editing technologies for human gene therapy JL Gori, PD Hsu, ML Maeder, S Shen, GG Welstead, D Bumcrot Human gene therapy 26 (7), 443-451, 2015 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:YOwf2qJgpHMC

Structural basis for the RNA-guided ribonuclease activity of CRISPR-Cas13d C Zhang, S Konermann, NJ Brideau, P Lotfy, X Wu, SJ Novick, … Cell 175 (1), 212-223. e17, 2018 Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:_Qo2XoVZTnwC

CRISPR-Cas component systems, methods and compositions for sequence manipulation F Zhang, DO BIKARD, L Cong, DBT Cox, P Hsu, W Jiang, LIN Shauiliang, … N/A Link: https://scholar.google.com/citations?viewop=viewcitation&hl=en&user=LhnUjoAAAAJ&citationforview=LhnUjoAAAAJ:5awf1xo2G04C

Co-authors

Silvana Konermann googlescholarauthorid silvanakonermann.md:JtlWgmQAAAAJ

Feng Zhang googlescholarauthorid fengzhang.md:B5QpZooAAAAJ

George Church googlescholarauthorid georgechurch.md:SfDzdgEAAAAJ

Jennifer Doudna googlescholarauthorid jenniferdoudna.md:YO5XSXwAAAAJ

Carolyn Bertozzi googlescholarauthorid carolynbertozzi.md:spPztUEAAAAJ

Eric Lander googlescholarauthorid ericlander.md:LXVfPc8AAAAJ