2022 Annual Report

Mechanisms of Genome Maintenance

Lab and Research Highlights:

• Dr. Richard Adeyemi named CCSG New Investigator Awardees: Dr. Adeyemi among the 2022 recipients of New Investigator support from the Cancer Center Support Grant.
  
• Dr. Adeyemi invited to The National Academy of Sciences Nineteenth Chinese-American Kavli Frontiers of Science Symposium.

Neurotransmission and Neuromodulation

Lab and Research Highlights:

• What can worms teach us about ourselves?: Why Dr. Jihong Bai looks for commonalities between tiny nematodes and us.
  
• Endophilin’s charged relationship with curved membranes: Breakthroughs into the properties that specify the function of endophilin and other curvature sensing proteins in neurons
• Dr. Bai wins McDougall Mentoring Award: This award recognizes and celebrates Fred Hutch faculty members who demonstrate a “dedication to and enthusiasm for mentoring their graduate students, postdoctoral fellows and/or medical fellows.”

Cell Division and Chromosome Segregation

Lab and Research Highlights: 

• Cellular choke artist: Aurora B doesn’t perform well under pressure: Utilizing new experimental strategies to understand the role of tension in kinetochore function.
• Cbf1 plays transcriptional traffic cop to balance centromere function: New understanding into how transcription influences the centromere’s function in cell division.
• Before cells divide, microtubule integrity and cell wall gene regulation are intertwined: The first global analysis of budding yeast translation in the presence and absence of microtubule disruption.
• Dr. Nairita Maitra awarded a Jane Coffin Childs postdoctoral fellowship.
• Daniel Barrero and advisor Dr. Sue Biggins awarded Gilliam Fellowship Award to advance diversity and inclusion in the sciences.

Viral Evolution

Lab and Research Highlights: 

• Coronavirus’ distant past reveals ancient roots of trait that could help them jump species: SARS-related coronaviruses with theoretical spillover potential more widespread than previously thought.
• Antibody, how do I escape thee? Let me count the ways: Predicting how combinations of mutations impact SARS-CoV-2 antibody escape.
• Leveling up SARS-CoV-2 neutralization assays: Receptor-binding domain antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2.
• Talking a lot but saying nothing: no link between viral transcription and progeny production: Influenza virus transcription and progeny production are poorly correlated in single cells.
• The evolving landscape of sarbecovirus ACE2 binding: Examining the ability of sarbecoviruses to bind ACE2, the evolutionary history of this interaction, and the potential for leaps across species boundaries.

Biophysics and RNA Biology

Lab and Research Highlights: 

• New therapeutic strategy turns a cancer’s advantage into its downfall: The Bradley Lab uses synthetic mRNA to trick tumors into manufacturing cancer-specific poison.
• The cell’s two-pronged approach to mitigating genetic errors: Nonsense-mediated mRNA decay is a more thorough and effectual mechanism than previously realized at limiting the production of mutant proteins.
  
• Engaging cancer cells in a high stakes game of spot the imposter: Transforming splicing factor mutations from a cancer’s strength into its weakness
  
• Dr. Robert Bradley named scientific director of Fred Hutch Translational Data Science Integrated Research Center: Computational biologist will lead efforts to integrate data science in bench-to-bedside cancer research.
  
• Jose Pineda successfully defends their dissertation “Ultra‐large‐scale genomics approaches to improve cancer therapeutic response”.
  
• Emma De Neef successfully defends their dissertation “Immune consequences and therapeutic targeting of disrupted RNA splicing in cancer”.
  

Systems Biology

Lab and Research Highlights:

• Using augmented reality to guide researchers’ hand in the lab: New work from the Brent Lab seeks to revolutionize laboratory training, using deep neural networks and augmented reality.

Sensory Systems and Stress

Lab and Research Highlights:

• New findings unravel the network of neurons responsible for the sense of smell: The Buck Lab makes insights into olfaction and its role in stress and appetite.

Cell Communication and Signal Transduction

Lab and Research Highlights:

• Dr. Melody Campbell named Pew Scholar: Structural biologist explores how cells interact with their surroundings.
• 'Blobology' no more: Cryo-EM microscopy opens up biology at atomic scales.
  
• Dr. Campbell featured on The Plunge Podcast: Campbell discusses the challenges of starting her lab during the COVID19 pandemic and why she fell in love with cryo-EM.
  

Cell Signaling and Migration

Lab and Research Highlights:

• Cell migration: it’s no walk in the park: New details emerge into the mechanisms underlying how cells move.
  
• Dr. Leisje Steenkiste joins the lab as a visiting Assistant Professor.
  

Transcriptional Control of Proliferation and Neoplasia

Lab and Research Highlights:

• The Myc network’s multiple functions in spermatogenesis: Discovering a role for the MYC protein network in cellular metabolism, differentiation, and survival during sperm production.
  
• MGA & MYC: mega-sized players in cancer progression: New insights into a MYC network member and its role in tumor progression and invasiveness.
• Dr. Robert Eisenman serves as chairman of the Scientific Review Board of the Starr Cancer Consortium and chairman of the Scientific Advisory Committee for the Center for Integrated Genomics.
  
• Yulong Su, postdoctoral research fellow, joins the lab.
  
• Drs. Brian Freie and Patrick Carroll promoted to Staff Scientists.
  

Virology of HIV

Lab and Research Highlights:

• License to Kill: Latency HIV-CRISPR pinpoints how to blow latent HIV’s cover: A powerful step forward in understanding, and potentially reversing, HIV-1 latency.
• A Passport to Cross-species Transmission: Crucial insights into the evolution of HIV and how it jumps species.
• A human-specific motif facilitates CARD8 inflammasome activation after HIV-1 infection: Exploring how CARD8 activation leads to cell death and promotes inflammatory responses to prevent pathogenesis.
• Dr. Jeannette Tenthorey receives Andy Kaplan Prize and Mathilde Krim Fellowship: Awards will help further Tenthorey’s research on HIV's host-cell interactions.
• Emily Hsieh successfully defends their dissertation “Using a CRISPR-based screen to study individual and combination molecular mechanisms of HIV-1 latency”.
  
• Vanessa Montoya successfully defends their dissertation “Genome scale identification of HIV dependency factors across multiple HIV-1 strains”.
  

Transcriptional Regulation

Lab and Research Highlights:

• Dr. Steven Hahn elected to American Academy of Microbiology: Hahn honored for his research revealing the fundamental properties of the molecular machinery that creates mRNA.
  
• Transcription factor binding: a sharp view of a fuzzy interaction: Identifying how transcription factors interact to control gene expression.
  
• Yeast Mediator facilitates transcription initiation at most promoters via a Tail-independent mechanism: Hahn Lab overturns long-standing model on the role of the transcription coactivator “Mediator” in genome-wide transcription.
  

Micronuclei and Nuclear Envelope Repair

Lab and Research Highlights:

• Chromosomes take fate into their own hands during micronucleus rupture: Discovering new characteristics that influence membrane stability in micronuclei.
  

Epigenetics

Lab and Research Highlights:

• License to Kill: Latency HIV-CRISPR pinpoints how to blow latent HIV’s cover: A powerful step forward in understanding, and potentially reversing, HIV-1 latency.
  
• Peeling back the layers of a cell’s epigenomic data: A new method for multi-epigenomic profiling.
• MulTI-Tag: your ticket to profiling chromatin: Novel techniques allows researchers to map multiple epigenetic features simultaneously.
  
• Dr. Steve Henikoff elected to American Academy of Arts and Sciences: Election honors Henikoff’s contributions to understanding of fundamental biology.
  
• Dr. Jay Sarthy receives Sunbeam Foundation and Burroughs-Welcome Awards.
  

Immunology and Microbiota

Lab and Research Highlights:

• Lessons from mom: How to be the best immune system you can be: Dr. Meghan Koch’s work in mice on how breast milk’s immune proteins shape infant immune system, long-term health could someday help human babies.
• Dr. Koch receives Kenneth Rainin Foundation Innovator Awards: Award supports high-risk research to advance the goal of predicting and preventing inflammatory bowel disease.
• Dr. Koch receives Hartwell Award: Award supports studies of breast milk antibodies on newborn growth, health.
• Dr. Koch receives Safeway Pilot Award: Funding helps investigations on immune education by the microbiota to help advance cancer therapy.

Protein Degradation

Lab and Research Highlights:

• Exploring the cellular pathways that remove unwanted proteins, and how they become mis-regulated in disease: Research from the Lehrbach Lab makes insights into the process of protein degradation and its involvement in aging, cancer, adult-onset neurodegenerative diseases, and rare genetic disorders.
• Dr. Katie Yanagi, postdoctoral research fellow, awarded a Japan-US Science Communication and Policy Fellowship, funded by The Japan Foundation.

Genetic Conflict

Lab and Research Highlights:

• Short H2A histones, part I: parental conflict at the evolutionary scale: Identify a gene at the center of a genetic conflict between mother and father with implications for the fitness of their offspring. 
• Histone variants: new versions of ancient genes: The discovery of several new and rapidly evolving histone genes in mammals.
• Dr. Harmit Malik elected to American Academy of Arts and Sciences: Election honors Malik’s contributions to understanding of fundamental biology.
• Dr. Malik receives Novitski Prize: Evolutionary biologist uses creative strategies to tackle genetic conflict.
• Dr. Malik Receives the 2022 'SASTRA-Obaid Siddiqi Award' for excellence in Life Sciences: Award recognizes Malik’s record of research and its impact in the discipline of Life Sciences.
• Dr. Pravrutha Raman, postdoctoral fellow, gets Washington Research Foundation fellowship and wins 4th annual Nancy Hutchison Mentoring award.
  
• Dr. Yu-Ying Phoebe Hsieh, postdoctoral fellow, receives Cystic Fibrosis Foundation fellowship.
  
• Dr. Ching-Ho Chang, postdoctoral fellow, receives Damon Runyon fellowship.
  
• Dr. Tamanash Bhattacharya, postdoctoral fellow, receives Helen Hay Whitney fellowship.
  
• Dr. Maria Toro Moreno, postdoctoral fellow, receives HHMI Hanna Gray fellowship.
  
• Dr. Jeannette Tenthorey, postdoctoral fellow, receives Retrovirology Andy Kaplan Prize and amfAR Mathilde Krim and Leading-Edge fellowship.
  
• Dr. Courtney Schroeder, lab alumni, started as Assistant Professor in Department of Pharmacology, UT Southwestern in October 2021.
  
• Dr. Kevin Forsberg, lab alumni, started as Assistant Professor in Department of Microbiology, UT Southwestern in September 2021.
  

Neurodevelopment

Lab and Research Highlights:

• Don’t lose your nerve: choosing the right path during axon regeneration: Crucial clues to uncovering how nerves are rebuilt after injury.

Wound Healing and Nuclear Architecture

Lab and Research Highlights:

• Beyond diabetes: the insulin pathway’s key role in cellular wound repair: Identifying an important new role for the insulin signaling pathway in coordinating wound repair.
• Dr. Susan Parkhurst named Mark Groudine Endowed Chair for Outstanding Achievements in Science and Service: Chair honors Parkhurst’s exceptional research into cells’ internal scaffolding, service to Fred Hutch.
• Justin Hui, Kerri Davidson, and Viktor Stjepić received Undergraduate Travel Awards from the Genetics Society of America.
  
• Kerri Davidson, Research Tech II, accepted to MD-PhD program at Yale University.
  
• Tessa Allen, Research Tech II, accepted to Neuroscience PhD program at the University of Colorado.
  

Developmental Systems

Lab and Research Highlights:

• Dr. James Priess shares Gruber Genetics Prize: $500K award honors contributions to understanding the genes and processes that control early development.
• Nuclear lipid droplets and nuclear damage in Caenorhabditis elegans: Priess Lab shows that nuclear fat is associated with hallmarks of nuclear damage, including rupture of the nucleus.

Neurobiology of Obesity

Lab and Research Highlights: 

• Finding the ‘sweet spot’: what hungry flies can teach us about human metabolism: The Rajan Lab discoveries how high-sugar diets disrupts hunger sensing in flies.
• New seed grant to Dr. Akhila Rajan from Brain Research Foundation: The seed grant will fund two years of research in the Rajan Lab, helping them explore the connection between fat storage and neurodegenerative disorders.
• NGMS MIRA award renewed for 5 years: Funding supports research on the cellular mechanisms of nutrient sensing.
• Dr. Kevin P. Kelly, postdoctoral fellow, receives the National Science Foundation’s Postdoctoral Research Fellowship in Biology to study a novel role for adipokines in gene regulation.
  

Metabolic Flexibility and Suspended Animation

Lab and Research Highlights:

• Promising, novel first-generation therapy, Faraday announces first patient enrolled in phase 3 trial for myocardial infarction: Spinning off from the research of the Roth Lab, Faraday Pharmaceuticals announced the beginning of a phase 3 trial of testing iodide for the treatment of heart attack.

Cell Proliferation and Fate

Lab and Research Highlights: 

• Peeling back the layers of a cell’s epigenomic data: A new method for multi-epigenomic profiling.
• SEACells: Inference of transcriptional and epigenomic cellular states from single-cell genomics data: New algorithm for identifying metacells; overcoming the sparsity of single-cell data, while retaining heterogeneity obscured by traditional cell clustering. 
• The Setty Lab awarded NIGMS R35 grant: Funding helps the lab illuminate the mechanisms that drive cellular differentiation through data-driven modeling of high-throughput single-cell data, providing a basis to decipher the dysregulation in disease and significantly boost the potential of cell engineering to produce treatment-grade cells and tissues.
• The Setty Lab welcomes its first graduate student to join the lab, Cailin Jordan.
  
• The Setty Lab awarded BBI Catalytic Collaboration Award and a TDS IRC New Collaboration Award.
  

Glia-Neuron Interactions

Lab and Research Highlights:

• Careful pruning guides neuron function: Accessory brain cells called glial cells nibble nerve cells to affect worm memory, behavior — even at the single-cell level.
• A little nervous system with big learning potential: How the worm C. elegans helps the Singhvi Lab make breakthroughs into the basis of learning and memory.
• Charging Up the Periphery: Glial Ionic Regulation in Sensory Perception: Sneha Ray explains the role that glia plays in sensory perception and how a deeper understanding into their function is essential to better understand sensorineural health, disease, and aging.
• Dr. Aakanksha Singhvi receives Klingenstein-Simons Fellowship Award in Neuroscience: Singhvi seeks to understand the molecules involved in glia-neuron communication, how glia influence neuron shape and function, and how dysregulations contribute to disease.
• Dr. Singhvi receives Evergreen Fund Pilot Award.
• Emily Teets, graduate student, awarded BMHA training grant.
• Violet Sorrentino, graduate student, awarded NSF-GRFP fellowship and CMB training grant.
  
• Stephan Raiders successfully defends their dissertation “Molecular Mechanisms of Glial Pruning.”
  

Gene Regulation and Genomic Integrity

Lab and Research Highlights:

• RecBCD enzyme and Chi recombination hotspots as determinants of self vs. non-self: Myths and mechanisms: Highschooler Suriyen Subramaniam collaborates with Dr. Gerry Smith to overturn previously held understanding of how E. coli recognize its own DNA.
• Host nucleases generate prespacers for primed adaptation in the E. coli type I-E CRISPR-Cas system: Global collaboration details the mechanisms of the CRISPR-Cas system and identifies the role of RecBCD.

Protein Structure and Design

Lab and Research Highlights:

• One gene, two functions in bacterial immunity: Characterizing BREX system leads to a surprising discovery about its function.
  
• Outpacing evolution: synthetic protein design for biomedical application: Designing thousands of new proteins with potentially important biomedical implications.
• Improving computational protein design for real-world applications: Engineering synthetic proteins that can act as scaffolds for drug display and delivery.
• Dr. Barry Stoddard marks his 30th anniversary at Fred Hutch. The Stoddard Lab was the first to move into Fred Hutch’s South Lake Union Campus in the early 1990s.
  

Translational Biophysics and Vaccine Design

Lab and Research Highlights:

• New method improves T-cell antigen discovery: The Strong group develops a streamlined method, called Artemis, to identify the specific parts of tumors and pathogens recognized by the cellular immune system. They are applying Artemis to improve immunotherapies and understand the function and evolution of cellular immunity.

Regulation of mRNA Translation and Stability

Lab and Research Highlights: 

• A nascent peptide code for translational control of mRNA stability in human cells: The Subramaniam Lab identifies an intrinsic role for the ribosome as a selectivity filter against the synthesis of bulky and aggregation-prone peptides.
• Translational buffering by ribosome stalling in upstream open reading frames: New discoveries into how ribosomes regulate the expression of proteins and implications for how protein production changes during cellular stress.
• 'Microprotein' researcher Maria Toro Moreno is named a Hanna Gray Fellow: Dr. Moreno wins prestigious award from the Howard Hughes Medical Institute.
• Dr. Matthew Chan, postdoctoral fellow, receives Mahan Computational Biology Fellowship.
  
• Dr. Rachael Bakker, postdoctoral fellow, receives National Science Foundation Postdoctoral Fellowship.
  
• Phil Burke successfully defends their dissertation.
  

Neuroimmunology

Lab and Research Highlights:

• Dr. Jhimmy Talbot receives a Kenneth Rainin Foundation Innovator Award: Award supports high-risk research to advance the goal of predicting and preventing inflammatory bowel disease.
• Fred Hutch Microbiome Research Initiative awards funding for two pilot projects: Dr. Talbot receives pilot funding from MRI for two projects exploring the microbiome and health outcomes.

Chromatin and Quiescence

Lab and Research Highlights:

• Chromatin fibers: oh what a tangled web we weave: How changes in chromatin structure affect gene expression during the process of quiescence.
• Dr. Pravrutha Raman, postdoctoral fellow, gets Washington Research Foundation fellowship and wins 4th annual Nancy Hutchison Mentoring award.
  
• Dr. Raman featured on NPR's Short Wave: "The Secret History of DNA": With help from researcher Pravrutha Raman, Short Wave producer Berly McCoy explains how DNA is stored in our cells and why the iconic double helix shape isn't what you'd see if you peeked inside your cells right now.