Editing biology to understand life

We work at the intersection of bioengineering and genomics to invent new tools for understanding and treating genetic disorders.

Team

Patrick D. Hsu, Ph.D.

Patrick Hsu is a Principal Investigator and Salk Helmsley Fellow at the Salk Institute for Biological Studies. His work aims to understand and manipulate the genetic circuits that control brain and immune cell function for the next generation of gene and cell therapies.

At the Salk, Patrick's research group integrates diverse approaches in synthetic biology, bioengineering, and genomics to develop new molecular technologies for genome and transcriptome engineering. CRISPR tools that systematically reverse-engineer cellular processes through rapid and precise perturbations enable causal links between genetic changes and fundamental disease mechanisms. Recently, the Hsu lab discovered and developed novel CRISPR systems that expand the gene editing toolbox beyond DNA to RNA, and continues to build new approaches for cell design and control. These insights will enable us to install cellular upgrades to combat neurodegeneration and cancer.

Patrick received his B.A. from the University of California, Berkeley, as well as A.M. and Ph.D. degrees from Harvard University. Working with Feng Zhang and Xiaowei Zhuang at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT, he contributed to the early development of CRISPR-Cas9 technologies for efficient and precise genome engineering in eukaryotic cells.

As a lead scientist at Editas Medicine, Patrick also directed preclinical discovery projects to translate these tools for treating human genetic disorders. He was recognized for these contributions in Forbes' 30 Under 30 and the NIH Early Independence Award. Patrick can be found on Twitter and Google Scholar.

Silvana Konermann, Ph.D.

Silvana is a neuroscientist and bioengineer. She received her B.S. in Biology from ETH Zürich and Ph.D. from MIT in Neuroscience, where she was a Hubert Schömaker Fellow. Her graduate work with Feng Zhang focused on developing new methods for manipulating brain gene expression using light and genome-scale transcriptional activation, for which she was awarded the 2015 Harold Weintraub Graduate Student Award. She was a Catharina Foundation Fellow, a winner of the 2017 Salk Women & Science Special Award, and is currently an HHMI Hannah Gray Fellow.

Silvana's top pet peeve: Swiss cheese, not Swiss cheese!

Peter Lotfy

Peter received his B.S. in Physiology & Neuroscience and M.S. in Biology from UCSD. He completed his thesis in the lab of Larry Goldstein, where his work focused on understanding the mechanisms of tau protein turnover in human neurons. He also developed a CRISPR-based system for conducting genome-wide genetic screens in human induced pluripotent stem cell-derived cell types.

Peter has two pugs and thousands of primers.

Jennifer Oki

Jennifer received her B.A. in Plant Biology at the University of California, Riverside and M.S. in Biochemistry and Molecular Biology from the University of Southern California. Her previous work focused on using differentiated embryonic stem cells as a model to study hippocampal development and regulation in embryogenesis. In her current work, she studies mechanisms of cellular degeneration from a neuro-immune perspective.

Jen has a pet tarantula and runs casual marathons on the weekend.

Nick Brideau, Ph.D.

Nick studied fly genetics at Cornell University, where as a graduate student, he identified the first Dobzhansky-Muller gene pair that satisfied a longstanding theory for genetic incompatibility and speciation. During his postdoctoral fellowship at the University of Oxford, Nick applied proteomic, biochemical, and molecular analyses to study X inactivation and chromatin remodeling.

Don't ask Nick about Crossfit, he'll tell you.

Tom Alsaigh, M.D.

Tom is currently an NIH KL2 clinician-investigator at the Scripps Translational Science Institute/TSRI. As an undergraduate at UCSD, Tom studied molecular mechanisms governing endothelial dysfunction. During medical school, he became an HHMI Medical Fellow at the Salk Institute and studied the cellular and molecular basis of neurovascular development. His current interests revolve around developing novel methods of treating vascular diseases using gene editing, and eventually bringing this technology directly to patients in the clinic.

You've never seen someone drink coffee like Tom, probably because his hobby is saving lives.

Nick Hernandez

Nick is an undergraduate student studying Biology at San Diego State University. His previous work at the Biomedical department of the Ensenada Center for Scientific Research and Higher Education focused on discovering the pharmacological potential of venoms isolated from sea anemone and marine cone snails. He is currently a stem cell intern through SDSU and the California Institute for Regenerative Medicine, studying the role of APOE in Alzheimer's disease models.

Nick is an amateur magician. He once turned a 2.5 hour drive to lab retreat into a 7 hour drive. Would it have been better the other way around?

Research

Rapid advances in DNA sequencing technologies over the past decade have transformed our ability to read the genome, epigenome, and transcriptome of all living organisms, illuminating the genetic building blocks and dynamics of biological systems. Human population genetics has augmented this knowledge with a wealth of genetic variation associated with disease susceptibility and drug response.

However, establishing causal linkages between genetic changes and cellular function requires the ability to rewrite or modulate endogenous genetic sequences and their numerous transcriptional and epigenetic states at a similar scale.

A major focus of our lab is to develop the molecular tools that make it possible to dissect and rewire these gene circuits. We are also applying these tools to study immune cells in the brain and periphery. Our goal is to uncover the biological mechanisms behind neurodegenerative and immune-related disorders, and exploit this new knowledge to develop therapeutic strategies that endow cells with genetic upgrades to combat disease.

Funding

Our work is supported by the Helmsley Charitable Trust, the NIH Director's Early Independence Award, the National Institutes on Aging, and the Salk Institute for Biological Studies.

Publications

Contact

Hsu Lab @ Salk
The Salk Institute for Biological Studies
Molecular & Cell Biology Laboratory (MCBL-P)
10010 N. Torrey Pines Rd
La Jolla, CA 92037

patrick@salk.edu

Salk Institute for Biological Studies

Join Us

Are you curious about the biological mechanisms underlying health and disease? Are you interested in creating and applying tools to engineer and repair life?

We are always looking for passionate, collaborative, and energetic scientists to work with us, whether you're an postdoc, grad student, undergrad, or research associate. If you're a molecular or computational biologist, neuroscientist, bioengineer, or really creative scientist of any variety, let's chat!

If you're interested in joining or visiting the lab, please email patrick@salk.edu with (1) a CV, (2) a short summary of your research background and interests, and (3) a list of 3 references (for postdoctoral candidates).


July 2018: We are seeking a Postdoctoral Fellow and Research Assistant to join an NIA-funded project to interrogate stem cell-derived 2D and 3D models of Alzheimer’s disease using high-throughput CRISPR genome editing and functional genomics screens. For Research Assistants, please note Application Instructions.


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