Dr. Jennifer Doudna is a member of the departments of Molecular and Cell Biology and Chemistry at UC Berkeley, the Howard Hughes Medical Institute, and Lawrence Berkeley National Lab, along with the National Academy of Sciences, and the American Academy of Arts and Sciences.
- Fellow, American Academy of Arts and Sciences (2003)
- Professor of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, the University of California, Berkeley (2003)
- Professor of Biochemistry and Molecular Biology, Department of Chemistry, the University of California, Berkeley (2003)
- Faculty, Biophysics Graduate Group, the University of California, Berkeley (2003)
- Faculty Scientist, Physical Biosciences Division, Lawerence Berkeley National Laboratory (2003)
- Member, National Academy of Sciences (2002)
- Member, Board of Trustees, Pomona College (2001)
- American Chemical Society Eli Lilly Award in Biological Chemistry (2001)
- R. B. Woodward Visiting Professor, Harvard University (2000-2001)
- Alan T. Waterman Award (2000)
- Investigator, Howard Hughes Medical Institute (1997)
- Searle Scholar, Kinship Foundation’s Searle Scholars Program (1996)
- Henry Ford II Professor of Molecular Biophysics and Biochemistry, Center for Structural Biology, Department of Molecular Biophysics and Biochemistry, Yale University (1994-2002)
- Lucille P. Markey Scholar in Biomedical Science, University of Colorado (1991-1994, Dr. Thomas R. Cech)
- Postdoctoral Research Fellow, Molecular Biology, Massachusetts General Hospital and Harvard Medical School (1989-1991, Dr. Jack W. Szostak)
- Ph.D. Harvard University (1989, Dr. Jack W. Szostak)
- B.A. Pomona College (1985, Dr. Sharon M. Panasenko)
Glioblastoma multiform (GBM) is one of the most common and aggressive forms of brain cancer, but current therapeutic treatments are limited. My research focuses on using the gene-editing CRISPR/Cas9 system in order to first further understanding of genes underlying tumor cell immortality in GBM, and second develop in vivo delivery methods to achieve CRISPR/Cas9 editing of GBM tumor cells, with the ultimate goal of inhibiting tumor growth.
Diverse CRISPR-Cas systems are now known to function as integral components of the immune repertoire of many microorganisms, with the currently known catalog of systems spanning two of the three domains of life and contributing to the capacity of these bacteria and archaea to thwart viral infection. Eukaryotes conspicuously lack endogenous CRISPR-Cas systems, but it is not yet known if these molecular surveillance complexes can be co-opted to achieve therapeutically relevant inhibition of viral infection in humans through direct interference with the genomes of human viruses. While investigating strategies to improve the therapeutic potential of CRISPR-Cas components, I will also examine our ability to temporally control the editing activity of diverse CRISPR effectors.
CRISPR-Cas-based genome editing tools enable the control of gene expression in cells, tissues and whole organisms. Although invaluable for experimental studies, translation of these advances into clinical therapeutics requires delivery of CRISPR-Cas proteins and guide RNA to disease-relevant organs in the body. All current in vivo delivery strategies have drawbacks including ineffective delivery to target tissue, prolonged nuclease expression leading to off-target damage, and clearance of edited cells by adaptive immune responses. I posit that viral infection strategies can be harnessed to overcome the challenges faced by the in vivo delivery of genome editing tools. In the Doudna laboratory, I am applying my background in viral engineering to create the next-generation of CRISPR-Cas delivery vehicles and translate these technologies into therapeutics. By merging virology with bioengineering, I aim to make these revolutionary genome-based treatments accessible to all people who can benefit.
The vast majority of microbial diversity remains unexplored due to the inability to cultivate most microbes in a lab. My research focuses on a group of uncultivated bacteria called the candidate phyla radiation (CPR), which comprises over 15% of Domain Bacteria. Currently, almost no experimental characterization of CPR bacteria has been performed and many identified genes have unknown biological function. My work focuses on cultivation, biochemical characterization, and ultimately genetic engineering of CPR bacteria.
The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins are an RNA-guided defense mechanism against foreign genetic elements in archaea and bacteria. The first step of CRISPR immunity is acquisition, wherein foreign DNA fragments are detected and integrated into the host cell’s chromosome. The precision of this process is instrumental in maintaining the CRISPR locus and host-genome integrity due to off-target integrations. I am interested in understanding the intricate mechanisms that underline the accuracy of the adaptation process.
The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems arose in bacteria and archaea as an adaptive innate immune response to combat viral infection. In Class 2 type II CRISPR systems, the single protein effector Cas9 is guided by a CRISPR-RNA to cleave complementary target sequences within foreign DNA. With biochemical and structural data to define their molecular mechanisms, Cas9 and the Class 2 type V effector, Cpf1, have been readily employed as tools for genome engineering. However, the CRISPR-Cas systems show remarkable diversity across microbial species, with the recent identification of highly divergent class 2 single effectors that share little to no resemblance to Cas9. My research focuses on understanding the molecular mechanisms of the expanding ‘CRISPR universe’ using biochemistry and X-ray crystallography.
Research interest1: LncRNAs play key regulatory roles in various cellular pathways. For example, Host lncRNAs NRON and NEAT1 strongly affect latent infection by exerting a rigorous regulation-cycle on HIV-1 transcripts and proteins. However, detailed 3D structural information is lacking. Leveraging the technical advantages of cryo-EM technology, I’m seeking to establish general methods to help researchers determine the 3D structures of lncRNAs more efficiently.
Research interest2: Various alternative Class2 Cas proteins from different organisms have been characterized that show a number of advantages with respect to SpyCas9. Understanding the structural basis for these special properties of different Cas proteins will greatly benefit the design of an optimized gene-editing tool. Furthermore, anti-CRISPR proteins have been identified as specific and genetically encodable ‘‘off-switches’’ for Cas9 which may help clinical difficulties and safety concerns, but the structural mechanism is yet unknown. I’m interested to explore the guide RNA-binding and DNA-targeting mechanisms for Class2 Cas proteins, and to determine, in atomic detail, how different typeII anti-CRISPR proteins control the activity of Cas9 proteins.
CRISPR-Cas systems are an ancient and widespread RNA-guided adaptive immune system in bacteria and archaea. My research focuses on how multisubunit Type III CRISPR-Cas complexes target transcriptionally active DNA and RNA of invading phages and plasmids. Using a combination of biochemistry and single-particle electron microscopy, I aim to uncover the mechanism of transcription-coupled target recognition by Type III complexes. Understanding how they find and destroy their targets will provide fundamental insights into RNA-guided immunity in prokaryotes, and could potentially lead to a tool that can detect or target actively expressed genes in heterologous systems, such as eukaryotic cells.
Bastian is a postdoctoral scholar in the Innovative Genomics Institute’s agricultural genomics branch. He started working on genome-editing in the food staple rice during his time as a Beachell-Borlaug International Scholar at Penn State. He now continues his efforts to improve disease resistance and yield of crops at UC Berkeley under supervision of Drs. Jennifer Doudna and Brian Staskawicz. Bastian’s first goal during his time at the Innovative Genomics Institute is to develop tools for precise genome-editing and accelerated plant breeding using advanced plant tissue culture and CRISPR methods. Another interest of him is to develop bioinformatic tools to avoid off-target editing in plants and to increase on-target activity. As ultimate goal, Bastian tries to develop an efficient gene repair system to easily change genetic information in crops to make them healthier and sturdier.
CRISPR-associated systems in bacteria and archaea can specifically bind and cut a sequence of DNA in a programmable, RNA-guided manner. For this reason, CRISPR effector nucleases, particularly Cas9 and Cas12a (AsCas12a) are promising tools for therapeutic genome editing. The challenges of controlling off-target cleavage events and editing outcomes of CRISPR-induced DNA breaks, however, must be overcome to realize their therapeutic potential.
Improved understanding of CRISPR effector behavior in live cells would provide insight into strategies for better control of CRISPR-Cas in human nuclei. A live-cell imaging platform, in which cells stably express nuclease-dead SpyCas9 fused to a HaloTag domain, has been successfully used to visualize Cas9 DNA interrogation in live mouse cell nuclei. Using this CRISPR imaging platform as a foundation, I am working to i) construct stable cell lines expressing WT and nuclease-dead variants of Cas9 and Cas12a, fused to a HaloTag domain for imaging ii) compare binding fidelity and DNA residence time of Cas9 and Cas12a when targeted to the same gene iii) image fluorescently labeled WT CRISPR effectors and human repair enzymes to map the sequence and duration of steps processing CRISPR-induced DNA breaks. Specifically, by measuring the lag time between binding of CRISPR effectors and binding of various individual repair enzymes on target DNA, I will spatiotemporally map substrate transfer from CRISPR-Cas to repair.
CRISPR-Cas (clustered regularly interspaced short palindromic repeats – CRISPR-associated proteins) systems typically provide bacteria and archaea with an adaptive immunity against foreign nucleic acids. Interestingly, many mobile genetic elements (MGEs, e.g bacteriophages and transposons) have recently been shown to possess their own CRISPR-Cas systems. Those MGE-borne CRISPR-Cas systems are believed to eliminate competing MGEs and some variants have been shown to sequence-specifically guide transposition events of their associated transposons. My research focuses on the biochemical and structural characterization of novel MGE-borne CRISPR-Cas systems, to understand their biological role and to eventually allow their translation into tools for genome editing and biotechnological applications.
CRISPR-Cas in Uncultured Microbes: The large majority of life has never been cultivated within the laboratory. This life can both be mined for new CRISPR-Cas systems and manipulated by these systems to facilitate understanding. My research focuses on the development of genetics, enabled by CRISPR-Cas, in communities of uncultured microorganisms. Secondarily, I look for new CRISPR-CAS and CRISPR-Cas-like defense systems within these same communities.
CRISPR-Cas enzymes are RNA-guided bacterial proteins widely used for genome editing and genetic manipulation in a wide range of cell types. Beyond correction of genetic mutations in human cells, CRISPR-Cas enzymes may have additional therapeutic value for eliminating specific bacterial species during infection. In order to realize their clinical potential, it is critical to maintain tight control over CRISPR-Cas genome editing activity to maximize editing efficiency while avoiding off-target editing. Natural inhibitors of Cas enzymes, known as anti-CRISPRs (Acrs), block Cas activity by a variety of mechanisms, suggesting the possibility of a much larger collection of CRISPR-Cas regulators that may occur across the microbial world. My aim is to identify novel mechanisms of CRISPR-Cas regulation using genomics and biochemistry.
Abby is a postdoctoral scholar in the California Institute for Quantitative Biosciences. She began studying the host immune response to bioengineered materials during her time as a graduate student at the University of Pittsburgh McGowan Institute for Regenerative Medicine. She now studies how the immune system responds to Cas proteins and delivery vectors to improve the efficacy of gene editing and to further translate the use of CRISPR systems for in vivo applications.
Glioblastoma (GBM) is a deadly disease that most people with this cancer died within two years of diagnosis despite decades of research on finding more effective treatments. With the recent development of CRISPR (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) proteins as easily accessible and programmable means of editing and regulating genes, I propose to directly leverage CRISPR-Cas as a therapeutic modality to eliminate GBM cells. I have two main research focuses 1) use CRISPR-Cas system to dissect mechanisms of tumorigenesis and identify therapeutic targets, and 2) develop in vivo delivery tools to target GBM stem-like cells, the main population responsible for tumor recurrence, using intracranial xenograft model of GBM.
While protein structures are commonly represented as a single set of 3D coordinates, most biological macromolecules rely heavily on conformational flexibility to effect their functions in solution. Cas effector complexes in particular undergo dramatic conformational movements during the process of RNA-guided nucleic acid targeting. I am broadly probing the energetic landscape of these dynamic interference complexes to better understand how their nuclease activity is regulated.
I joined the Doudna laboratory with an active interest in CRISPR/Cas9 technology and its potential to cure genetic neurological diseases. My current research focus is on Huntington’s Disease (HD) which is a neurodegenerative disorder caused by a genetically dominant, CAG trinucleotide expansion in the Huntingtin (HTT) gene. I am interested in the development of CRISPR-RNP technology for the therapeutic reduction of mutant Huntingtin protein. I am also working on expanding the delivery of this technology to increase gene editing in the central nervous system and be applicable to other disease targets.
Former Postdoctoral Associates
Senior Bioengineer, Arbor Biotechnologies
Assistant Adjunct Professor, Department of Cellular & Molecular Pharmacology, School of Medicine, University of California, San Francisco; Staff Research Investigator, Gladstone Institutes
Assistant Professor, Tel Aviv University
Assistant Professor, UCSF
Assistant Professor, University of Rochester Medical Center
Postdoctoral Fellow, Garvan Institute of Medical Research in Sydney
Editor, Cell Magazine
Assistant Professor, University of Texas, Austin
Scientist, Global Blood Therapeutics
Assistant Professor, Harvard Medical School, Kranzusch Lab
Senior Scientist, Pfizer
Assistant Professor, ShanghaiTech
Assistant Research Fellow, Academica Sinica
Principal Investigator, Wilson Lab, UC Berkeley
Scientist at Genentech
Senior Manager, Technology Development at Guardant Health
Project Scientist, Berkeley Lab
Assistant Professor, Institute of Biochemistry, University of Zurich
Assistant Professor, Montana State University
Assistant Professor, Iowa State University
Assistant Professor, Univ. of Wisconsin, Madison
Lecturer, Molecular & Microbial Biosciences, The University of Sydney
Assistant Professor of Biological Chemistry, Johns Hopkins University School of Medicine
Assistant Professor, Seoul National University
Associate Director /Laboratory Leader-Protein Production, MorphoSys AG
Assistant Professor, University of Southern Alabama
Associate Professor, MIT
Associate Professor, UC Davis
Staff Scientist, Bio-Rad Laboratories
Professor, Scripps Research Institute
Associate Professor, The Scripps Research Institute
Senior Scientist, Baxalta, Inc.
Associate Professor, Cornell University
Service Architect,Hitachi Consulting
Staff Scientist, Genentech
Research Director, University of Strasbourg, Strasbourg, France
Professor, University of Colorado, Boulder, CO
Lab Head, NIH
Sr. Scientist, Boehringer Ingelheim Inc.
Former Graduate Students
Co-founder, Chief Discovery Officer, Mammoth Biosciences
Co-founder, Chief Research Officer, Mammoth Biosciences
Science Media Communications Innovative Genomics Institute
Scientist Arrakis therapeutics
Data Scientist Forsite Capital
Communications Manager Innovative Genomics Institute
Postdoc, Weissman lab, UCSF
Postdoc, Susan Lindquist lab, MIT
Assistant Professor, Columbia University
Senior Scientific Researcher, Genentech
President/CEO, Caribou Biosciences
Instructor, Diablo Valley College
Assistant Professor, Mount Holyhoke College
Postdoctoral Fellow, UCSF
Postdoc. Research Assoc., R. Stevens Lab, Scripps Research Institute
Resident, Virginia Commonwealth University Department of Radiology
Director of Marketing Azure Biosystems, Inc
Staff Scientist, Health Program National Resources Defense Council
Global Director of Customer Success, LinkedIn Learning
Associate Professor, UC Irvine
Principal Scientist, Merck & Co., Inc.
Owner and Proprietor, MadeWithMolecules.com
Prof., UC Berkeley