2025 Annual Report

Mechanisms of Genome Maintenance

Lab and Research Highlights:

• Rose Bosire, postdoctoral fellow, and Jodiene Johnson, graduate student, won grants from Fusion Conferences to attend the Targeting the DNA Damage Response for Cancer Therapeutics Conference. They were selected for the cutting-edge nature of their research and to better disseminate their work.

• Kristian Choate, graduate research assistant, joined the Adeyemi Lab.

• Kristian Choate was selected for support through the Cellular and Molecular Biology Training Grant.

Chromatin Structure

Lab and Research Highlights:

• Frogs help Fred Hutch find the shape of small things
  The Arimura Lab brings frogs back to Fred Hutch after a long absence to study the structure of DNA-linked molecular complexes that change during the cell cycle and malfunction in cancer and other diseases.

• Yasu Arimura was named a CCSG New Investigator Awardee. The funding will support his research understanding DNA damage and repair by using Cryo-EM to visualize non-homologous end joining, a key DNA repair process, in its native cellular context.

• Gardenia Sanchez, postbac, joined the Arimura Lab.

Neurotransmission and Neuromodulation

Lab and Research Highlights:

• Dr. Jihong Bai was awarded a five-year NINDS R01 for his proposal "Signaling Pathways that Modulate Neuronal Activity."

• Dr. Jihong Bai was awarded five-year NINDS R01 renewal for his proposal "Molecular Interplay of Endocytic Proteins."

• Manuel Rosero graduates with their PhD in Molecular and Cellular Biology after successfully defending their dissertation “Thermosensory Neurons Mediate Tactile-Dependent Locomotion Modulation in C. elegans.”

Cell Division and Chromosome Segregation

Lab and Research Highlights:

• The Biggins Lab celebrates their 25th anniversary and all the amazing colleagues that have made it such a wonderful place to do research over its past and present.

• Snapping the histone CENP-A in place for high-fidelity cell division requires supervision.
  New results can shed light on protein DNA interactions and how they can be dysregulated in diseases including cancer.

• Direct observation of interdependent and hierarchical kinetochore assembly on individual centromeres.
  The Biggins Lab provides an unprecedented view of the kinetochore assembly process and the regulatory events that control its order and timing.

• Darren Mallett graduates with their PhD in Molecular and Cellular Biology after successfully defending their dissertation “Uncovering the mechanisms that control unattached kinetochore clustering.”

• Kat Wardrup, postdoctoral research fellow, joined the Biggins Lab.
  Theresa Wechsler, postdoctoral research fellow, joined the Biggins Lab.
  Abby Jurasin, research technician and postbaccalaureate scholar, joined in the Biggins Lab.
  Jamie Zuckerman, graduate student, joined the Biggins Lab.

Viral Evolution

Lab and Research Highlights:

• Managing mountains of genomic data
  Tools invented in the Bloom Lab are helping researchers analyze the enormous global database of genomic sequences of the virus that causes COVID-19 to better understand how pathogens evolve and spread.

• Dr. Jesse Bloom was named a fellow of the American Academy of Microbiology in recognition of his scientific achievement and contributions to microbiology.

• Dr. Jesse Bloom successfully renewed his appointments as a Howard Hughes Medical Institute Investigator.

• The Bloom Lab receives two Bill and Melinda Gates Foundation awards for their projects “Deep mutational scanning of HIV Env to inform antibody development” and “Deep mutational scanning of RSV F to understand escape from candidate clinical antibodies”.

• Caroline Kikawa and Caleb Carr, graduate students, were awarded F30 Individual Predoctoral NRSA Fellowships.

• Dr. Arjun Aditham, postdoc, left the Fred Hutch in June. Arjun joined the Protein Engineering team at SystImmune.

• Dr. Will Hannon, data scientist, left the Fred Hutch to join the Allen Institute as a Scientist at SeaHub.

Biophysics and RNA Biology

Lab and Research Highlights: 

• RNA “typos” can highlight leukemia cells for immune attack
  Looking beyond DNA, scientists find possible “surgically targeted” option for splicing factor-mutant blood cancers that lack effective immunotherapies.

• Muscleblind proteins revealed to have a new role as anti-tumor agents
  The Bradley Lab identifies an unexpected player in tumor immune recognition.

• Siegen McKellar graduates with their PhD in Molecular and Cellular Biology after successfully defending their dissertation “Exploring Regulators of Tumor-immune Interactions: Chorionic Gonadotropin Beta and Major Vault Protein.”

Sensory Systems and Stress

Lab and Research Highlights:

• The Buck Lab pioneers new investigations into how the immune systems works to protect the brain from viral infection in the olfactory system and the long-term risks of this protection failing.

Cell Communication and Signal Transduction

Lab and Research Highlights:

• Molecular exaptation by the integrin αI domain
  New discoveries from the Campbell Lab reveals the evolutionary and biochemical basis of expanded cellular communication in vertebrates.

• Jeremy Hollis, graduate student co-mentored in the Campbell and Malik Labs, wins 2025 Harold M. Weintraub Graduate Student Award.

• Adam Nguyen, graduate student, wins NIH F31 award to study structure of a key protein that helps blood vessels grow, but also helps cancer spread when it malfunctions.

• Matthew Chan, Postdoc in the Campbell and Subramaniam labs, received an IIRC Innovation Award for his project on characterizing chimeric T-cell receptors for the informed design of next generation receptors for cellular therapy.

• Eva Alleman, a Graduate Student, was selected for support through the UW Cellular and Molecular Biology Training Grant.

• The Campbell Lab hosted the first annual Seattle Area CryoEM Meeting on Oct 9, 2025.

• Eva Alleman, graduate student, joined the Campbell Lab.

• Zeqi (Chelsea) Wang, research technician, joined the Campbell lab.

• The Campbell Lab wins first place in the most artistic category in this year’s pumpkin carving contest.

Cell Signaling and Migration

Lab and Research Highlights:

• Cell biologist and former Fred Hutch division leader Dr. Jonathan Cooper retires
  Cooper sustained the distinct culture of Basic Sciences for four decades.

• Dayoung Kim, Postdoctoral Research Fellow in the Cooper lab, will be joining Scisco Genetics. She will also be continuing her research project as a non-employee, in collaboration with Chan Mi Lee in the Beronja lab.

Transcriptional Control of Proliferation and Neoplasia

Lab and Research Highlights:

New light on the workings of a major driver of multiple cancers

The Eisenman lab has long focused on the MYC transcription factor known to be an essential regulator of normal growth in all cells, but which becomes genetically altered in multiple types of cancer. Over the last few years, the lab has shown that MYC does not act alone but rather functions in the context of a network of related transcription factors. For example, MYC needs to form a dimer with the small MAX protein order to bind to DNA. However MAX dimerizes with other transcription factors that antagonize MYC functions, some of which act as tumor suppressors. Moreover, a MAX-like protein known as MLX forms dimers with nutrient sensing transcription factors that also critically influence MYC function. We have shown that these proteins, which together comprise the MYC Network, are in dynamic balance and interact with and recruit other cellular factors to modulate broad programs of gene expression controlling growth and proliferation. Importantly we have found that tumor cells driven by deregulated MYC acquire a dependency on other network members indicating that MYC cancers may have a unique vulnerability that can be exploited using small molecule inhibitors.

Showcasing new strides in rare cancer research

Fred Hutch’s 4th Rare Cancers Symposium featured the collaborative research of the Eisenman and MacPherson Labs working to understand the basis for longstanding findings that MAX deletion or mutational inactivation occurs in a rare subset of neuroendocrine cancers. We developed a mouse model and demonstrated that MAX loss-of-function resulted in a marked increase in the progression of small cell lung cancer as well as thyroid and pituitary neuroendocrine cancers. Our molecular and genomic analyses comparing MAX wildtype to MAX deleted tumors showed that MAX loss triggers destabilization of MYC, causes alterations in metabolism, and results in a striking shift in genomic occupancies by other members of the MYC network which appear to recapitulate MYC’s transcriptional signature. Our work has revealed MAX as a broad suppressor of neuroendocrine tumorigenesis through its ability to maintain a balance of genomic occupancies among the diverse transcription factors in the MYC network.

• Erin Ramsey presented a poster at the EMBO Epitranscriptomics Meeting in Heidelberg.

• Bob Eisenman described the lab’s research at a Banbury Conference and at the History of Cancer Genetics conference at Cold Spring Harbor, N.Y.

• The Eisenman lab received a Sloan Precision Oncology Award.

Virology of HIV

Lab and Research Highlights:

• Virologist and HIV expert Dr. Michael Emerman retires
  During his 36-year career at Fred Hutch Cancer Center Michael Emerman made fundamental discoveries about HIV, the retrovirus that causes AIDS.

• Dr. Michael Emerman receives the Fred Hutch Conclave Education, Teaching, and Mentoring Award.
  Emerman received the award in honor of his 35 years of exceptional mentorship of the next generation of scientists, training over 20 postdoctoral fellows and 26 graduate students.

• Ancient heritage discovered for a family of antiviral proteins
  In collaboration with the Malik Lab, the Emerman Lab discovers the earliest ancestor for Mx antiviral proteins, finding that Mx-like proteins pre-date the interferon system in animals, exist in invertebrate species, and can even be found in plants and fungi.

Transcriptional Regulation

Lab and Research Highlights:

• Rewriting the story about the molecules that turn genes on and off
  The Hahn Lab discovers that most transcription factors in budding yeast don’t follow the textbook example of binding close to the genes they regulate

• Drs. Steve Hahn and Lakshmi Mahendrawada sit down with the Double-stranded Podcast to discuss their recent paper showing the low overlap of transcription factor DNA binding and regulatory targets.

Epigenetics

Lab and Research Highlights:

• Dr. Steve Henikoff receives 55th Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research.

• New methods reveal cancer mechanism in ancient genes
  The Henikoff Lab, in collaboration with the Holland Lab, discovered that overproduction of DNA packaging material predicts aggressive brain and breast tumors, which could lead to cheaper diagnostic tests and new drug therapies.

• Kami Ahmad, Staff Scientist in the Henikoff Lab, received new subaward project issued from a NIH SBIR grant entitled “Scalable and quantitative chromatin profiling from formalin-fixed paraffin embedded samples”. Working with Epicypher Inc, he will develop further technical improvements for FFPE-CUTAC profiling of tissue samples.

• Ron Paranal, research associate in the Henikoff Lab, was appointed as a "Paul Calabresi K12 Scholar." Ron will be building on the Henikoff Lab’s recent discovery that aberrant replication-coupled histone production can predict cancer outcomes, with the goal of developing a liquid biopsy approach to enable earlier cancer detection and more accurate prognostication.

• Weifang Wu, postdoctoral fellow, was awarded Cold Spring Harbor’s Asia Fellowship at the CSHA Systems Biology of Gene Regulation and Genome Editing Meeting.

• Weifang Wu, postdoctoral fellow, shares first prize at this year’s Basic Sciences retreat poster session.

• Kevin Nguyen, postbaccalaureate student, joined the Henikoff Lab.

• Ron Paranal, research associate, joined the Henikoff Lab.

Immunology and Microbiota

Lab and Research Highlights:

• Oh, the microbes you’ll meet!
  The Koch Lab discovers a biological mechanism sprung in the first week of life that trains a mouse pup’s immune system to tolerate harmless gut bugs and new foods.

• Dr. Meghan Koch was named a Burroughs Wellcome Fund 2025 Investigator in the Pathogenesis of Infectious Disease. The award will provide five years of support for her research challenging the paradigm of maternal IgG antibodies by understanding their role in subverting infant immunity to enteric infection.

• Dr. Meghan Koch received a Bench-to-Bedside Adult Oncology Research Award for her project “Assessing the gut microbiome and microbiota-specific immunity in Merkel cell carcinoma” in a collaboration with Paul Nghiem, MD. The award facilitates transdisciplinary bench-to-bedside adult oncology cancer research.

• Brittany Jimena, graduate student in the UW Immunology PhD Program, joined the Koch Lab and was selected for support through the UW Cellular and Molecular Biology Training Grant. She is working on the project funded by the Burroughs Wellcome Fund.

• Kat Ramos, graduate student in the UW MCB PhD Program, joined the Koch Lab joint with Dr. Paul Ngheim. She is working on the project funded by the Bench-to-Bedside Adult Oncology Research Award.

Lab and Research Highlights:

• eIF1 and eIF5 dynamically control translation start site fidelity
  New discoveries from the Lapointe Lab uncover mechanisms of translation and protein production showing how the interplay between two initiation complexes tunes the fidelity of start site recognition, which has broad connections to health and disease.

• Chris Lapointe was selected as a 2025 Rita Allen Foundation Scholar and received a five-year award for his proposal "From the beginning to the end: Translation initiation and its control by the 3'UTR."   Since 1976, the Rita Allen Foundation has provided funding for more than 200 early-career scientists, fostering creative research with above-average risk and promise.

• Oliver Nicholson, postbaccalaureate research tech, left Fred Hutch in June to pursue a graduate degree in Biochemistry at the University of Wisconsin.

• Niseema Pachikara, staff scientist, left Fred Hutch in June to pursue her medical degree at Hackensack Meridian School of Medicine.

• Sydney McGuire, Post-baccalaureate Scholar in the Lapointe lab, won a Best Poster Award at the RNA Society Annual Meeting in San Diego.

• Christopher Lapointe was awarded a five-year Maximizing Investigators Research Award (MIRA) for Early-Stage Investigators.

• The Lapointe Lab takes second place in the most artistic category in this year’s pumpkin carving contest.

Protein Degradation

Lab and Research Highlights:

• Elyse Christensen, graduate student in the Lehrbach Lab, received a competitive position on the Biological Mechanisms of Healthy Aging Training Grant (the “BMHA” NIH T32 Training Grant). In addition, Elyse also won the prestigious University of Washington Graduate School's UWRA Patricia Dougherty Fellowship in Aging.

• Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.
  The Lehrbach Lab shows that ‘sequence editing’ fine-tunes SKN-1A/Nrf1-dependent gene regulation to enable adaptation to different stress conditions.

Genetic Conflict

Lab and Research Highlights:    

• Evolutionary cell biologist Dr. Grant King named a Hanna Gray Fellow
  Long fascinated by life seen and unseen, King awarded eight years of funding to finish postdoctoral training at Fred Hutch and establish an independent lab.

• Dr. Harmit Malik successfully renewed his appointments as a Howard Hughes Medical Institute (HHMI) Investigator. The HHMI Investigator Program currently supports nearly 300 scientists around the United States. Each HHMI investigator remains at their home institution while being an employee of HHMI, receiving significant financial support for their research and labs.  
  
  
• Ancient heritage discovered for a family of antiviral proteins
  In collaboration with the Malik Lab, the Emerman Lab discovers the earliest ancestor for Mx antiviral proteins, finding that Mx-like proteins pre-date the interferon system in animals, exist in invertebrate species, and can even be found in plants and fungi.

• For dual-host alphaviruses, it’s a balancing act
  The Malik Lab sheds light on the mechanisms of genome regulation employed by alphaviruses that informs our fundamental understanding of how they function as well as our capacity to combat them when they threaten human health.

• Aida de la Cruz, lab manager, has been awarded the 2025 Nancy Hutchison award for mentoring from SPAC based on commendations by her trainees. Aida is the third recipient of the Hutchison Mentoring Award in the Malik lab (after postdoc Pravrutha Raman and staff scientist Janet Young). Aida is also the brainchild behind the many prize-winning Malik lab pumpkins over the years.

• Nelia Perry joined the Malik lab as a Research Technician as part of the Postbaccalaureate Scholar Program.

• Megan Levy, Molecular and Cellular Biology Graduate Student, joins the Malik Lab.

• Dillon Conner, Research Technician in the Malik lab, departed Fred Hutch in early September to begin graduate school at the University of Washington as part of their Molecular Medicine and Mechanisms of Disease program.

• Ching-Ho Chang and Yu-Ying Phoebe Hsieh left the Malik lab to start their independent labs in the Institute of Molecular Biology and the Institute of Plant and Microbial Biology, respectively, at the Academia Sinica in Taiwan.

• Tiia Freeman, postbac, shares first prize at this year’s Basic Sciences retreat poster session.

• Rebecca Ferreira Alves, postbac, shares second prize at this year’s Basic Sciences retreat poster session.

• The Malik Lab wins first place in the most scientific category in this year’s pumpkin carving contest.

Neurodevelopment

Lab ad Research Highlights:

• Veronica Sikora, graduate student, joined the Moens Lab and won a position on UW’s Cell and Molecular Biology training grant.

• Dr. Cecilia Moens is serving as the president of the International Zebrafish Society and the director of the Society for Developmental Biology Science Communication Internship Program.

Wound Healing and Nuclear Architecture

Lab and Research Highlights:

• Nuclear Envelope Budding: Getting large macromolecular complexes out of the nucleus
  The Parkhurst Lab summarizes the current understanding of nuclear envelope budding, a process where molecules too large to pass through nuclear pore complexes can still traffic across the nucleus.

• Sage Brill, research technician and postbaccalaureate scholar, joined the Parkhurst Lab.

Developmental Systems

Lab and Research Highlights:

• The Priess Lab led new investigations into understanding the mechanisms of tissue deterioration during aging and how this process can be slowed or prevented to extend lifespans.

Neurobiology of Obesity

Lab and Research Highlights:

• A sugar-loaded diet doesn’t just go to your hips; it might also stop your brain from taking out the trash.
  The Rajan Lab uncovered how changes in adipocyte metabolism directly influence brain health via a novel adipo-glial pathway.

• Akhila Rajan was awarded a multi-year funded R01 (RF1 mechanism) from the NIA to advance the lab’s work on fat–brain communication and brain senescence.

• Shannon Marschall, postbac, shares second prize at this year’s Basic Sciences retreat poster session.

Metabolic Flexibility and Suspended Animation

Lab and Research Highlights:

• Cold air makes oxygen toxic for worms
  The Roth Lab made discoveries into the relationship between temperature and oxidative stress showing that hypothermia shields against the effects of anoxia, and anoxia blunts the stress of hypothermia, resulting in a higher survival rate for both lethal conditions than for either one alone.

Cell Proliferation and Fate

Lab and Research Highlights:

• Comparing phenotypic manifolds with Kompot: Detecting differential abundance and gene expression at single-cell resolution.
  The Setty Lab introduces a novel computational framework called Kompot, that helped them reveal how aging reshapes cellular identity and regulatory programs across the hematopoietic landscape.

• Mapping molecules of an unsung brain cell
  The Singhvi and Setty Labs teamed up to create a gene-expression map of glial cells in tiny worms, adding the missing component that completes for the first time an atlas of the entire nervous system of a multicellular adult animal at the molecular level.

• Connor Finkbeiner, graduate research assistant, was awarded a F31 titled: Deciphering the Dynamic Coordination of Chromatin Accessibility and Gene Expression to Uncover the Mechanisms of Cellular Differentiation.

• Dominik Otto, postdoc, was awarded a K99 entitled "Computational Strategies for Deciphering Cellular Differentiation and Cancer Progression."

• Cailin Jordan, graduate research assistant, was awarded a F31 titled: Epigenomic Dynamics of Clonal Hematopoiesis.

• Elana Thieme, graduate student joint with Stan Lee Lab was awarded the ASH Graduate Hematology Award. 

• The Setty Lab takes third place in the most scientific category in this year’s pumpkin carving contest.

• Claire Mills, graduate student, shares first prize at this year’s Basic Sciences retreat poster session.

• Graduate students Connor Finkbeiner, Sarah Huang, and Tomas Bencomo, share third prize at this year’s Basic Sciences retreat poster session.

Glia-Neuron Interactions

Lab and Research Highlights: 

• Mapping molecules of an unsung brain cell
  The Singhvi and Setty Labs teamed up to create a gene-expression map of glial cells in tiny worms, adding the missing component that completes for the first time an atlas of the entire nervous system of a multicellular adult animal at the molecular level.

• The Singhvi Lab was awarded a Phase 1 Grant from the Washington Research Foundation.

• Maria Purice, postdoctoral research fellow, started her own laboratory at Oregon State University in Corvallis, OR. She is currently an Assistant Professor in the Department of Biochemistry and Biophysics and the Linus Pauling Institute.

• German Rojas, graduate student, successfully defended his thesis, and is now a postdoctoral fellow at UW.

• Sean Manning, research technician, left the lab to start his PhD graduate studies at the University of Utah.

• Emily Teets, graduate student, shares second prize at this year’s Basic Sciences retreat poster session.

• Katie Schneider, undergraduate student, successfully completed her honors thesis in MCDB at UW.

Gene Regulation and Genomic Integrity

Lab and Research Highlights:

• Debunking the dogma that RecBCD nuclease destroys phage.
  For decades, it has been repeatedly claimed that the potent bacterial helicase-nuclease RecBCD destroys foreign DNA, such as that of phages, but repairs and recombines cellular DNA. New discoveries from the Smith Lab refute these claims, and show RecBCD repairs broken DNA that can recombine but destroys DNA that cannot recombine and recycles the nucleotides.

• Mug20-Rec25-Rec27 binds DNA and enhances meiotic DNA break formation via phase-separated condensates.
  The Smith Lab, in collaboration with the Chi Lab at the Institute of Biological Chemistry, Academia Sinica, makes discoveries into how linear element proteins enhance meiotic DNA double-strand break formation and provide a paradigm for studies in other species.

• Lambdoid phages with abundant Chi recombination hotspots reflect diverse viral strategies for recombination-dependent growth
  The Smith Lab discovers that phages lacking their own recombination systems have compensated by becoming enriched in Chi sites, enabling them to use the host's RecBCD to fulfill the requirement for recombination to efficiently replicate. This study highlights the importance of recombination for phage survival and the diversity of strategies to achieve it.

• Chi hotspot control of RecBCD enzyme requires a RecB AQ1 tether–RecC groove crosspoint interaction.
  The Smith Lab identifies a novel point that is critical for Chi’s site-specific stimulation of recombination in Escherichia coli. Deleting or changing even a single amino acid in this crosspoint dramatically reduces Chi hotspot activity. These results expand on the Smith lab’s previous work, resulting in a total of fourteen identified points responsible for RecBCD control.

Lab and Research Highlights:

• Capsule-Based Single-Cell Genome Sequencing
  The Srivatsan Lab presents a novel semi-permeable capsule that isolates single cells while allowing selective biomolecular exchange, retaining larger biomolecules like genomic DNA while permitting smaller molecules to pass through. Using this technique the lab achieved high sensitivity and specificity in detecting genomic variants and successfully reconstructed cellular genealogies from cells harboring the hypermutator polymerase ε allele.

• Sanjay Srivatsan received the Chan Zuckerberg Initiative Award to help them develop methods for the high throughput synthesis and assembly of genes.

• Sam Sgrizzi and Dustin Mullaney, graduate students, join the Srivatsan Lab.

• Sam Sgrizzi, graduate student, was awarded a UW Genome Training Grant to support their research developing capsule-based platforms for highly parallel, gene-length DNA assembly to investigate the functional impact of clinically relevant protein variants.

• The Srivatsan Lab takes second place in the most horrific category in this year’s pumpkin carving contest.

Protein Structure and Design

Lab and Research Highlights: 

• Paddles, door handles, and a DNA-modifying protein called BsaXI
  The Stoddard Lab determines the structure of DNA-free and DNA-bound BsaXI, a restriction modification enzyme.  Their discoveries expand our understanding of the biochemical underpinnings of how these diverse enzymes work and evolve and open the possibility of harnessing their functions for more practical purposes.

• Computational design of sequence-specific DNA-binding proteins
  The Stoddard Lab, in collaboration with the University of Washington’s Baker Lab, developed and tested a computational method for the design of small DNA-binding proteins that recognize short specific target sequences. This method provides a route to readily deliverable sequence-specific DNA-binding proteins for gene regulation and editing.

• PglZ from Type I BREX phage defence systems is a metal-dependent nuclease that forms a sub-complex with BrxB.
  The Stoddard Lab, in collaboration with Durham University’s Blower Lab, make new discoveries into the BREX system that bacteria use to defend themselves from viral infection. They identified a stable BREX sub-complex and generated and validated structural models that help inform its function, revealing its activity to be metal dependent.

Translational Biophysics and Vaccine Design

Lab and Research Highlights:

• Artemis: Mass Spectrometry-Based Identification of MHC-Presented Peptides Across Alleles, Classes, and Species Using Soluble Single-Chain MHC Constructs.
  The Strong Lab refined their Artemis technique that enables the identification of up to tens of thousands of allele-specific peptides per run for peptidomics, ligandomics, therapeutic targeting, and motif analyses.

• The Strong Lab patents a novel chelating platform for the delivery of radionuclides.
  The technique can be used to deliver radionuclides for imaging and therapeutic purposes.