Keystone Symposia

Fairmont Chateau Whistler Floorplan

This meeting took place in 2023



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Genomic Instability and DNA Repair (X1)


Organizer(s) Katharina Schlacher, Irene Chiolo and Ralph Scully
March 19—23, 2023
Fairmont Chateau Whistler • Whistler, BC Canada
Abstract Deadline: Dec 28, 2022
Scholarship Deadline: Dec 28, 2022
Discounted Registration Deadline: Jan 18, 2023

Sponsored by (Cell Research), Chinese Society for Cell Biology and Pfizer Inc.


Summary of Meeting:
DNA replication and repair are critical processes that initiate, orchestrate, and affect a broad range of fundamental physiological reactions, ultimately promoting cell division, genome stability, and proper cellular physiology. Reflected in this, genes acting in DNA replication/repair and genome stability are required for disease suppression, and direct therapy responses. Their failure is correlated with genome instability, cancer, neurological defects, developmental delays, aging, metabolic disorders, inflammation and immune responses, and therapeutic drug reactions. Rooting in and extending from the rich history of deep mechanistic understanding of the field, this Keystone conference will highlight the latest advances and emerging concepts in the field, aspiring to prompt rich discussions in particular with its implications for medical biology, disease and treatment strategies.

View Scholarships/Awards
No registration fees are used to fund entertainment or alcohol at this conference

Conference Program    Print  |   View meeting in 12 hr (am/pm) time


The meeting will begin on Sunday, March 19 with registration from 16:00 to 20:00 and a welcome mixer from 18:00 to 20:00. Conference events conclude on Thursday, March 23 with a closing plenary session from 17:00 to 19:00, followed by a social hour. We recommend return travel on Friday, March 24 in order to fully experience the meeting.

SUNDAY, MARCH 19

16:00—20:00
Arrival and Registration (4pm Start)

MacDonald Foyer
18:00—20:00
Welcome Mixer
No registration fees are used to fund alcohol served at this function.

MacDonald Foyer

MONDAY, MARCH 20

07:00—08:00
Breakfast

Frontenac / Empress
08:00—09:30
Welcome and Keynote Session (Joint) (8am Start)

MacDonald Ballroom
* Katharina Schlacher, MD Anderson Cancer Center, USA

* Laura Sepp-Lorenzino, Intellia Therapeutics, USA

Titia de Lange, Rockefeller University, USA
APOBEC3-Dependent Kataegis and TREX1-Driven Chromothripsis During Telomere Crisis

Jennifer A. Doudna, University of California, Berkeley, USA
The CRISPR Revolution: The Power and Promise of Gene Editing

Coffee Break

09:50—11:30
Genome Instability and Cancer (Joint) (9:50am Start)

MacDonald Ballroom
* Katharina Schlacher, MD Anderson Cancer Center, USA

André Nussenzweig, NCI, National Institutes of Health, USA
Genome Instability in Post-Mitotic Cells

Stephen C. West, Francis Crick Institute, UK
DNA Repair – Structures and Mechanisms

Agnel Sfeir, Memorial Sloan Kettering Cancer Center, USA
Restricting MMEJ to Mitosis: The Role of RHINO

11:30—17:00
On Own for Lunch

11:30—13:00
Poster Setup

Frontenac / Empress
13:00—22:00
Poster Viewing

Frontenac / Empress
14:30—16:30
Workshop 1: The Past and Future of DNA Repair/Replication (2:30pm Start)

MacDonald AB
* Kristina Schmidt, University of South Florida, USA

Michelle Swift, Dana-Farber Cancer Institute, USA
Dynamics of the DYNLL1/MRE11 Complex Regulates DNA End Resection and Recruitment of the Shieldin Complex to DSBs

Yuan He, Northwestern University, USA
Structure Basis of DNA Double-Strand Break Repair by NHEJ

Sinem Usluer, Medical University of Graz, Austria
Disordered Regions Mediate the Interaction of p53 and MRE11

Justine Sitz, University of Copenhagen, Denmark
Untangling the Genome Maintenance Functions of BRCA1 during Unperturbed Cell Cycle

Brian B. Rodemoyer, University of South Florida, USA
A Novel Interaction between the Bloom's Syndrome DNA Helicase BLM and an Interphase-specific Condensin II Complex Aids in Maintaining Genome Stability


Following Session is for Precision Genome Engineering (X2)

14:30—16:30
Roundtable Discussion: Genome Editing Ethics (2:30pm Start)

MacDonald CDEF
* Fyodor D. Urnov, University of California, Berkeley, USA

Sekar Kathiresan, Verve Therapeutics, USA

Jennifer A. Doudna, University of California, Berkeley, USA

Anna Kwilas, Food and Drug Administration, USA

Natalia Gomez-Ospina, Stanford University, USA

16:30—17:00
Coffee Available

MacDonald Foyer
17:00—19:00
Fork Protection and Cancer Therapy (5pm Start)

MacDonald AB
* Alessandro Vindigni, Washington University, USA
Mechanisms of Replication Fork Recovery in BRCA-deficient Tumors

* Sharon B. Cantor, University of Massachusetts Medical School, USA
Replication Gaps Underlie BRCA Deficiency and Therapy Response

Li Lan, Massachusetts General Hospital, USA
Understanding and Targeting R-Loops and mRNA-Dependent DNA Repair in Cancer

Andrew Elia, Massachusetts General Hospital, Harvard Medical School, USA
Short Talk: Regulation of Replication Fork Remodeling by RFWD3

Priyanka Verma, Washington University, USA
Short Talk: Communication between Base Damage and Replication-fork Remodeling Dictate Responses to PARP Inhibitor Therapy in BRCA-mutant Cancer


Following Session is for Precision Genome Engineering (X2)

17:00—19:00
Natural Editing and Repair Mechanisms (5pm Start)

MacDonald CDEF
* Toni Cathomen, University Medical Center Freiburg, Germany
Quantitative Evaluation of Chromosomal Rearrangements in Gene-Edited Human Stem Cells by CAST-Seq

Anna Kwilas, Food and Drug Administration, USA
Regulatory Approach for Gene Therapies Incorporating Human Somatic Genome Editing A CBER Perspective

Jacob E. Corn, ETH Zürich, Switzerland
Short Talk: TREX1 Restricts CRISPR-Cas9 Genome Editing in Human Cells

Chance Meers, Columbia University, USA
Short Talk: Transposon-encoded DNA Endonucleases use Guide RNAs to Selfishly Bias their Inheritance

Dahlia Rohm, Duke University, USA
Short Talk: Targeted Activation of the Imprinted PWS Locus via CRISPR/Cas9-based Epigenome Editing

19:00—20:00
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.

Frontenac / Empress
19:30—22:00
Poster Session 1 (7:30pm Start)

Frontenac / Empress

TUESDAY, MARCH 21

07:00—08:00
Breakfast

Frontenac / Empress
08:00—11:00
Nuclear and Chromatin Dynamics in DNA Repair (8am Start)

MacDonald AB
* Irene Chiolo, University of Southern California, USA
DNA Repair Mechanisms in Heterochromatin

Matthias Altmeyer, University of Zurich, Switzerland
Dynamics and Functions of DNA Repair Compartments

Coffee Break

Karim Mekhail, University of Toronto, Canada
Nuclear Dynamics in DSB Repair from Yeast to Humans

Philipp Oberdoerffer, Johns Hopkins University, USA
Epigenetic Control of Base Excision Repair as a Cancer Vulnerability

Marton Tibor Kovacs, Institut Curie, France
Short Talk: DNA Damage-induced Nuclear Envelope Rupture: A New Cancer Vulnerability

Aline Marnef, CNRS, France
Short Talk: DSB-induced RNA:DNA Hybrid Accumulation Arise from Transcriptional Repression Correlates with Resection


Following Session is for Precision Genome Engineering (X2)

08:00—11:00
Plant and Animal Science Gene Editing Applications and Regulatory Path (8am Start)

MacDonald CDEF
Yi Jin, Inari Agriculture, USA
Seeding Change through Genome Editing with Inari's SEEDesign (TM) platform

* Rodolphe Barrangou, North Carolina State University, USA
CRISPR Applications and Implications in Ag and Forestry

Coffee Break

Irina A. Polejaeva, Utah State University, USA
Advancing Large Animal Model Development using CRISPR/Cas 9 Dditing

John D. Laurie, Agriculture and Agri-Food Canada, Canada
Improved Plant Regeneration and Cas9 Cleavage Detection for Gene Editing in Wheat

Katie Willis, Imperial College London, UK
Autosomal Editors for Efficient Genetic Biocontrol

11:00—17:00
On Own for Lunch

11:00—13:00
Poster Setup

Frontenac / Empress
13:00—22:00
Poster Viewing

Frontenac / Empress
14:30—16:30
Workshop 2: New Approaches and Technologies to Study Genome Stability (2:30pm Start)

MacDonald AB
Maga Rowicka, University of Texas Medical Branch, USA
Quantitative DSB Mapping and Computational Modeling of Mechanisms of DSB Formation

Jeroen van den Berg, Hubrecht Institute, Netherlands
Acceleration of Genome Replication Uncovered by Single-cell Nascent DNA Sequencing

Neesha Kara, Babraham Institute, UK
Genome-wide Mapping of DNA Replication and Damage in Senescence using TrAELseq

Robin Sebastian, NIH/NCI/CCR, USA
Chromatin Topology Restricts DNA Replication at Double-strand Breaks

Xia Ding, Pfizer, Inc., USA
Cohesin Instability at Replication Forks Leads to Accumulation of Toxic G-quadruplex Structures and Confers PARPi Sensitivity

Anoek Friskes, Netherlands Cancer Institute, Netherlands
Dynamic, Higher-order Filament Formation to Facilitate DNA Repair

* Kyungjae Myung, Institute for Basic Science, South Korea
Precision Targeting Tumor Cells using Cancer specific InDel-mutations with CRISPR

Peter Ly, University of Texas Southwestern Medical Center, USA
Mitotic Clustering of Pulverized Chromosomes from Micronuclei

16:30—17:00
Coffee Available

MacDonald Foyer
17:00—19:00
Inflammation and Genomic Instability (5pm Start)

MacDonald AB
Karl-Peter Hopfner, Ludwig-Maximilians-University Munich, Germany
Structures of MRE11 and cGAS

Katharina Schlacher, MD Anderson Cancer Center, USA
Mitochondrial and Nuclear BRCA/FANC DNA Replication Stability in Disease and Cancer

* Roger Greenberg, University of Pennsylvania, USA
Genome Instability and Inflammation

* Julia Sidorova, University of Washington, USA
Short Talk: Innate Immunity Mediator STING Modulates Nascent DNA Metabolism at Stalled Forks in Human Cells

Julia Li, University of California San Diego, USA
Short Talk: Hidden in our Own Genome: A Previously Missing Link between Epstein Barr Virus and Cancer


Following Session is for Precision Genome Engineering (X2)

17:00—19:00
Delivery of Gene Editors: Potency, Biodistribution, Safety (5pm Start)

MacDonald CDEF
* Christian Dombrowski, Intellia Therapeutics, USA

Daniel J. Siegwart, University of Texas Southwestern Medical Center, USA
Multiplexed SORT LNPs for Enhancing CRISPR/Cas Gene Editing Cancer Therapy through Modulating Tumor Mechanical Properties

Charles Gersbach, Duke University, USA
Intended and Unintended Consequences of in vivo Editing

Jennifer R. Hamilton, University of California, Berkeley, USA
Short Talk: Cell Type-programmable CRISPR-Cas9 Delivery for Human T Cell Engineering

Lauren Goetsch, Mekonos, Inc, USA
Short Talk: Utilizing Surface-Functionalized Nanoneedles for Physical Cargo Delivery into Cells

19:00—20:00
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.

Frontenac / Empress
19:30—22:00
Poster Session 2 (7:30pm Start)

Frontenac / Empress

WEDNESDAY, MARCH 22

07:00—08:00
Breakfast

Frontenac / Empress
08:00—11:00
Genome Editing and DNA Repair (Joint) (8am Start)

MacDonald Ballroom
* Matthew Porteus, Stanford University School of Medicine, USA

Maria Jasin, Memorial Sloan Kettering Cancer Center, USA
Genome Modification by Natural and Artificial DNA Breaks

* Tanya T. Paull, University of Texas at Austin, USA
Regulation of DNA Double-Strand Break Repair and Oxidative Stress Signaling

Coffee Break

Daniel Durocher, Lunenfeld-Tanenbaum Research Institute, Canada
Genome Kintsugi

David Pellman, Dana-Farber Cancer Institute, USA
Mechanisms Driving Rapid Genome Evolution

Petr Cejka, Institute for Research in Biomedicine, Switzerland
Short Talk: Mechanism of DNA End Sensing by the MRE11 Complex: Implications for CRISPR Based Genome Editing and Telomeres

Gregory Davis, Sangamo Therapeutics, USA
Short Talk: Epigenetic Editing and Gene Regulation Using Designed Zinc Finger Proteins

11:00—17:00
On Own for Lunch

11:00—13:00
Poster Setup

Frontenac / Empress
13:00—22:00
Poster Viewing

Frontenac / Empress
14:30—16:30
Panel Discussion: Addressing COVID-19-Related Challenges for Women in Science (2:30pm Start)

MacDonald AB
Tanya T. Paull, University of Texas at Austin, USA

* Irene Chiolo, University of Southern California, USA

* Katharina Schlacher, MD Anderson Cancer Center, USA

Xiaolan Zhao, Memorial Sloan Kettering Cancer Center, USA

Helle D. Ulrich, Institute of Molecular Biology, Germany

Titia de Lange, Rockefeller University, USA


Following Session is for Precision Genome Engineering (X2)

14:30—16:30
Workshop (2:30pm Start)

MacDonald CDEF
* Matthew Porteus, Stanford University School of Medicine, USA

* Laura Sepp-Lorenzino, Intellia Therapeutics, USA

Romina Marone, University of Basel, DBM, Switzerland
Function-preserving Single Amino Acid Substitutions Shield Hematopoietic Stem and Progenitor Cells from CD117 Targeted Immunotherapy in vivo

Gabriele Casirati, Boston Children's Hospital/Dana Farber Cancer Institute, USA
Multiplex Epitope-Engineered HSPCs to Enable multi-target CAR-T Cell Immunotherapy for Acute Myeloid Leukemia

Samuele Ferrari, Vita-Salute San Raffaele University, Italy
Uncovering Upsides and Pitfalls of Base and Prime Editing in Hematopoietic Stem Cells

Ayal Hendel, Bar Ilan, Israel
Multiplex HDR for Correction Simulation of SCID by CRISPR Genome Editing in Healthy Donor Human HSPCs

Sean McCutcheon, Duke University, USA
CRISPR-based Epigenome Editing Screens Identify Transcriptional and Epigenetic Regulators of Human CD8 T Cell Function

16:30—17:00
Coffee Available

MacDonald Foyer
17:00—19:00
Replication Coupled Repair (5pm Start)

MacDonald AB
* Helle D. Ulrich, Institute of Molecular Biology, Germany
When the Fork Meets the Cytoskeleton - Functions of Myosin VI in DNA Repair and Replication Stress

Xiaolan Zhao, Memorial Sloan Kettering Cancer Center, USA
Integrative Analysis Reveals Unique Structural and Functional Features of the Smc5/6 Complex

* Ralph Scully, Beth Israel Deaconess Medical Center, USA
Stalled Fork Repair in Health and Disease

Shyam K. Sharan, National Cancer Institute, USA
Short Talk: DNA Mismatch Repair Independent Role of MLH1 in Suppressing Genomic Instability in BRCA2-Deficient Cells

Anna Malkova, University of Iowa, USA
Short Talk: Unraveling Mutagenic Potential of Break-induced Replication


Following Session is for Precision Genome Engineering (X2)

17:00—19:00
Editing Technology Development (5pm Start)

MacDonald CDEF
* Gregory Davis, Sangamo Therapeutics, USA

Alex Marson, Gladstone Institutes, University of California, San Francisco, USA
A Functional CRISPR Dissection of Gene Networks Controlling Human Regulatory T Cell Identity

Cecilia Cotta-Ramusino, Tessera Therapeutics, USA
Gene Writing: A New Genome Engineering Technology

Avencia Sanchez-Mejias, Integra Therapeutics, Spain
Short Talk: Characterization and Deployment in vivo of FiCAT Genome Writer

Steve E. Glenn, Integrated DNA Technologies, USA
Short Talk: Engineering an Improved Protein-Based HDR Enhancer

Y. Bill Kim, Pairwise, USA
Short Talk: A Novel Mechanistic Framework for Precise Sequence Replacement Using Reverse Transcriptase and Diverse CRISPR-Cas Systems

19:00—20:00
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.

Frontenac / Empress
19:30—22:00
Poster Session 3 (7:30pm Start)

Frontenac / Empress

THURSDAY, MARCH 23

07:00—08:00
Breakfast

Frontenac / Empress
08:00—11:00
RNA Functions in Genome Stability (8am Start)

MacDonald AB
* Karlene A. Cimprich, Stanford University, USA
A Novel Function for the DNA Replication Fork Remodeler HLTF in Genome Maintenance

Fabrizio d'Adda di Fagagna, IFOM ETS – The AIRC Institute of Molecular Oncology, Italy
RNA Synthesis at DNA Lesions

Coffee Break

* Francesca Storici, Georgia Institute of Technology, USA
RNA-Directed DNA Double-Strand Break Repair in Yeast and Human Cells

Eric J. Brown, Perelman School of Medicine, University of Pennsylvania, USA
Impact of DNA Repeat Transcription on ATR Inhibitor-driven Genomic Breaks

Clara Bonnet, Institut Curie, France
Short Talk: An RNA-protein Interaction at DNA Replication Forks

Amélie Fradet-Turcotte, Université Laval, Canada
Short Talk: FIRRM is a Novel Regulator of Interstrand Crosslink Repair


Following Session is for Precision Genome Engineering (X2)

08:00—11:00
Ex vivo Gene Edited Cell Therapies (8am Start)

MacDonald CDEF
* Pietro Genovese, Dana-Farber Cancer Institute, USA

Fyodor D. Urnov, University of California, Berkeley, USA
From N=1 to N=all: a Platform Approach to CRISPR-Cas Therapies for Disorders of Hematopoiesis

Natalia Gomez-Ospina, Stanford University, USA
Engineering the Blood to Treat the Brain Genome Editing

Coffee Break

Simon N. Chu, University of California, San Francisco, USA
Developing a Genome Editing Strategy to Deliver Alpha-globin Transgene to Alpha Thalassemia Major Hematopoietic Stem Cells

Dave Vereide, Umoja Biopharma, USA
Short Talk: Arming Induced Pluripotent Stem Cells with a Synthetic Receptor Enables Massive Production of Cytotoxic Innate Lymphocytes for “off-the-shelf” Cancer Immunotherapies

Matthew Porteus, Stanford University School of Medicine, USA
Sickle Cell Disease Clinical Program

11:00—17:00
On Own for Lunch

15:00—16:30
Career Roundtable (Joint) (3pm Start)

MacDonald CDEF
Tanya T. Paull, University of Texas at Austin, USA

Cecilia Cotta-Ramusino, Tessera Therapeutics, USA

Karl-Peter Hopfner, Ludwig-Maximilians-University Munich, Germany

Anna Kwilas, Food and Drug Administration, USA

16:30—17:00
Coffee Available

MacDonald Foyer
17:00—18:45
Genomic Instability and Cancer II (5pm Start)

MacDonald AB
* Susan M. Rosenberg, Baylor College of Medicine, USA
The DNA Damageome and Cancer

Filippo Rosselli, Gustave Roussy, France
From DNA Repair to Translation: When the Maintenance of Genetic Stability Turns to the Maintenance of Proteostasis

George Galea, European Molecular Biology Laboratory, Germany
Short Talk: The Golgi Complex is a Regulatory Hub for DNA Repair

Junjie Chen, University of Texas MD Anderson Cancer Center, USA
Short Talk: Targeting DNA Damage Responsive Pathways in Cancer Therapy

Susi Bantele, University of Copenhagen - CPR, Denmark
Short Talk: Heritable Changes in Chromatin Function after DNA Double-Strand Break Repair

Xabier Vergara, Netherlands Cancer Institute, Netherlands
Short Talk: Widespread Chromatin Context-dependencies of DNA Double-strand Break Repair Proteins


Following Session is for Precision Genome Engineering (X2)

17:00—18:45
In vivo Gene Editing Drug Development (5pm Start)

MacDonald CDEF
* Laura Sepp-Lorenzino, Intellia Therapeutics, USA
Realizing the Promise of CRISPR Therapeutics: Clinical Update from In Vivo Programs

Sekar Kathiresan, Verve Therapeutics, USA
Clinical Programs of Base Editors for Cardiovascular Disease

Christiano Alves, Massachusetts General Hospital, USA
A Permanent Genetic Treatment for Spinal Muscular Atrophy using Base Editors

18:45—19:00
Meeting Wrap-Up: Outcomes and Future Directions (Organizers) (6:45pm Start)

MacDonald AB

Following Session is for Precision Genome Engineering (X2)

18:45—19:00
Meeting Wrap-Up: Outcomes and Future Directions (Organizers) (6:45pm Start)

MacDonald CDEF
19:00—20:00
Social Hour with Lite Bites
No registration fees are used to fund alcohol served at this function.

Frontenac

FRIDAY, MARCH 24

08:00—08:00
Departure


*Session Chair †Invited, not yet responded.



Keystone Symposia thanks our Sponsors(s) for generously supporting this meeting:

Chinese Society for Cell Biology, (Cell Research) Pfizer Inc.

We gratefully acknowledge the generous grant for this conference provided by:


National Institutes of Health

Grant No. 1R13CA278260-01

Funding for this conference was made possible (in part) by 1R13CA278260-01 from the National Institutes of Health. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.


We gratefully acknowledge additional support for this conference from:

New England Biolabs, Inc.

We appreciate the organizations that provide Keystone Symposia with additional support, such as marketing and advertising:


Click here to view more of these organizations


Special thanks to the following for their support of Keystone Symposia initiatives to increase participation at this meeting by scientists from underrepresented backgrounds:


Click here to view more of these organizations


If your organization is interested in joining these entities in support of Keystone Symposia, please contact: John Monson, Director of Corporate Relations, Email: johnm@keystonesymposia.org,
Phone:+1 970-262-2690

Click here for more information on Industry Support and Recognition Opportunities.

If you are interested in becoming an advertising/marketing in-kind partner, please contact:
Josh May, Director, Technology and Digital Media, Email: joshuam@keystonesymposia.org,
Phone:+1 970-262-1179