2023 STTR 10-Year Anniversary Retreat

8:30 - 9:30 am

Breakfast & Registration

Check-in for the day and connect with fellow STTR members! 

9:30 -9:40 am

Opening Remarks 

Eric Holland, MD, PhD                                                                                                                     
STTR Director; Senior Vice President and Director, Human Biology Division; Endowed Chair in Cancer Biology, Fred Hutch

9:40 - 10:00 am

Precision Oncology Testing in 2023: Time to go Big? 

Colin Pritchard, MD, PhD                                                                                                                 
Professor, Co-Director, Genetics and Solid Tumors Laboratory, University of Washington

Precision oncology is here, and many cancer patients are benefiting from this new paradigm.  Next generation sequencing (NGS) has enabled increasingly sophisticated cancer tests for tumor profiling to guide treatment and for assessment of inherited cancer risk.  Since 2012, the FHCC and UW have offered clinical NGS testing through the OncoPlex program.  In this presentation, I will focus on the growth of this program over the past decade, including aspects of workflow, assay design, and applications to research. I will highlight uses for paired somatic (tumor) and germline (inherited) testing, liquid biopsy, and the intersection with digital pathology and AI.  The talk will cover what will be needed to continue to expand testing services in order to meet the rapidly growing clinical demand and facilitate enterprise-wide research.

10:00 - 10:20 am

Precision Oncology Assay Development: Whole Genome Sequencing From FFPE Tissues

Alex Zevin, PhD                                                                                                                 
Genomics Director, Fred Hutch

Parallel whole genome sequencing (WGS) and mRNA expression profiling has emerged as a powerful diagnostic tool enabling personalized medicine. This presentation will focus on efforts through the Fred Hutch Genomics and Bioinformatics Shared Resource towards development of a sample-to-answer analysis service for WGS and mRNA profiling from FFPE tissues.

10:20 - 10:40 am

The (Slow, Painful) Evolution of the NCI Acute Myeloid Leukemia Precision Medicine Initiative

Jerald Radich, MD                                                                                                           
Professor, Translational Science and Therapeutics Division; Kurt Enslein Endowed Chair, Fred Hutch

Discussing the 3+ year process of trying to develop a nation-wide  “precision medicine” program. What could go wrong?

10:40 - 11:00 am

Storing, Sharing and Analyzing Scientific Data With the Cirro Data Platform

Samuel Minot, PhD                                                                                                                    
Staff Scientist, Microbiome Research Initiative, Vaccine and Infectious Disease Division, Fred Hutch

Biomedical research has been revolutionized by modern technologies like genome sequencing, proteomics, and flow cytometry. These assays provide unparalleled insights, but also present a growing challenge for cost-effective storage, secure sharing with collaborators, and scalable computational analysis. The Cirro data platform has been developed by the Data Core (part of Fred Hutch Shared Resources) to help streamline the management of data produced by complex scientific instrumentation using modern cloud computing infrastructure and an accessible web interface.

11:00 - 11:30 am

Morning Refreshment Break

11:30 - 11:50 am

Classifying Tumor Phenotypes From Cell-Free DNA For Precision Oncology 

Gavin Ha, PhD                                                                                                                 
Assistant Professor, Herbold Computational Biology Program, Public Health Sciences Division, Human Biology Division, Fred Hutch

An accurate diagnosis of the tumor histology is essential for clinical care. Aggressive tumor phenotypes can emerge through subtype changes and lineage plasticity as major mechanisms of treatment resistance in cancer. Therefore, distinguishing tumor phenotypes has clinical relevance in view of therapeutic response, but the need for a biopsy to diagnose tumor histology can be challenging.

11:50a - 12:10p

In Situ Chromatin Profiling of Formalin-Fixed Paraffin-Embedded Samples

Steven Henikoff, PhD
Professor, Basic Sciences Division, Fred Hutch

Formalin Fixed Paraffin Embedded (FFPE) sample preparation has been the preferred method for long-term preservation of biological material for decades. However, the severe chromatin damage from long exposure to high concentrations of formaldehyde has made genomic studies difficult and expensive. We have developed a simple CUT&Tag workflow for mapping gene promoters and enhancers that yields high-quality data able to distinguish tumor types. The high efficiency and low cost of CUT&Tag can now be applied to ongoing and retrospective clinical and research FFPE samples.

12:10p - 12:30p

Melding Publicly Available RNASEQ Data To Create Landscapes For Cancer

Sonali Arora, MS                                                                                                       
Bioinformatics Analyst, Fred Hutch

As costs for performing RNASeq continues to decline with increasing technological advances, more and more tumors will be sequenced, and additional tumor banks will be created with the underlying goal to understanding cancer’s complexity. The wealth of knowledge that that already exists in publicly available datasets such as those described here (GTEx, TCGA, CGGA, CBTN) is remarkable. Individually these datasets comprise of well-defined biologically similar set of patient samples and allow the analysis in exquisite resolution of genetic changes from one sample to the next. . By integrating multiple datasets while correcting for batch effects, such as with the Brain-UMAP presented here, we can harness the power of multiple datasets.

12:30p - 2:00p 

Lunch & Museum Tour

Grab a bite to eat and then head down to explore the museum!

Take a ride on one of the flight simulators!

2:00  - 2:35 pm 

Keynote Address: Working Together To Build a Data Resource and AI Engine for Precision Oncology 

Jeff Leek, PhD                                                                                                                               
Vice President & Chief Data Officer; Professor, Biostatistics Program, Public Health Sciences Division; J. Orin Edson Foundation Endowed Chair, Fred Hutch      

2:35p - 2:45p

Keynote Address: The Sloan Precision Oncology Institute: An Operating System to Catalyze Personalized Cancer Prevention and Treatment

Peter Nelson, MD                                                                                                   
Vice President, Precision Oncology; Professor, Human Biology Division; Director, Sloan Precision Oncology Institute; Stuart and Molly Sloan Precision Oncology Institute Endowed Chair, Fred Hutch   

Thanks to generous gifts from Stuart and Molly Sloan, and the Bezos family, the Fred Hutch Cancer Center has been given an extraordinary opportunity to build and advance the next generation of cancer prevention and treatment strategies. This presentation will describe the initial structure and goals of the Sloan Precision Oncology Institute, with the intent to engage the research community in scientific partnerships to achieve meaningful advances in cancer outcomes.     

2:45 - 3:45 pm 

Poster Session 

Catch up on new scientific research across our groups, learn about ways our Office of Translational Research and Shared Resource teams can support your work, and hear about opportunities to engage with our external partners.

Vote for your favorite scientific poster – the top poster will win a team lunch for their lab!

3:45 - 4:05 pm

RIT1: A New RAS-Pathway Oncogene in Lung Cancer

Alice Berger, PhD                                                                                               
Associate Professor, Human Biology Division; Assistant Professor, Herbold Computational Biology Program; Public Health Sciences Division; Innovators Network Endowed Chair, Fred Hutch       

Mutations in the RAS pathway are a hallmark of lung adenocarcinoma, the most prevalent subtype of lung cancer. Mutations in oncogenes such as KRAS and EGFR have proven to be important drug targets and biomarkers in lung cancer. Dr. Berger’s work has identified mutation of RIT1 as a non-canonical RAS-activating event in lung cancer. Today she will present recent work aimed at understanding the role of RIT1 in lung cancer and the search for targetable vulnerabilities in RIT1-mutant lung cancer.   

4:05 - 4:25 pm

Translational Research Program in Cancer Disparities

Ulrike (Riki) Peters, PhD, MPH                                                                                              
Professor and Associate Director, Public Health Sciences Division; Professor, Cancer Prevention Program; Fred Hutch 40th Anniversary Endowed Chair, Fred Hutch             

Provide an overview of the Translational Research Program on Colorectal Cancer Disparities (TRPCD) which is developed to address the high colorectal cancer incidence and mortality rates of African American and Alaska Native people as well as disparities experienced in Hispanic people. Ongoing and planned research as part of a SPORE application aim to investigate knowledge gaps in a) molecular tumor profiling and microbial characterization of colorectal cancer across racially and ethnically diverse populations; b) identification of patients with elevated mortality risk; c) discovery and validation of novel molecular/biological markers related to risk of lethal disease; and d) development of novel therapeutic interventions.  Current efforts include establishing a robust Developmental Research Program and developing a biospecimen and data repository of over 1000 colorectal cancer patients with equal number of African American, Alaska Native, Hispanic/Latinx, and non-Hispanic White patients. This multi-institutional research effort is based on strong collaborative across the Alaska Native Tribal Health Consortium, Alaska, Cedars Sinai Samuel Oschin Comprehensive Cancer Institute, California, Fred Hutch, Washington, and Ochsner Clinical Foundation, Louisiana.     

4:25 - 4:45 pm 

The Intersection Between Structural, Environmental, and Racial Inequities in Prostate Cancer

Yaw Nyame, MD, MS, MBA                                                                                                   
Assistant Professor, Department of Urology, University of Washington School of Medicine; Assistant Member, Public Health Sciences Division, Fred Hutch

This presentation evaluates the relationship between place and health and highlights the lack of adequate data to evaluate how environment intersects with cancer risk and outcomes in prostate cancer.

4:45 - 5:05 pm 

PARP Inhibitors For Therapy of Ovarian Cancer: Optimizing Response and Minimizing Risk 

Elizabeth Swisher, MD                                                                                                  
Co-leader, Breast and Ovarian Cancer Research Program, University of Washington/Fred Hutchinson Cancer Consortium; Professor, Division of Gynecologic Oncology, University of Washington School of Medicine; Affiliate Investigator, Clinical Research Division, Fred Hutch

PARP inhibitors have been approved for the maintenance therapy of all ovarian carcinomas following response to frontline platinum based chemotherapy. PARP inhibitors have been associated with a 2-3 fold increased risk of therapy related AML and MDS (therapy related myeloid neoplasa or TMN).  Recently, the FDA  expressed concerns that in the recurrent setting there are observations of non-significant detriments in overall survival, leading to the withdrawal of some FDA indications for PARP inhibitor therapy of ovarian cancer.  This had led to increased focus on identifying those patients most likely to benefit from therapy as well as identifying those at risk of TMN. In this presentation, biomarkers of response and TMN will be reviewed.

5:05 - 5:15 pm

Closing Remarks

Snehal Joshi, PhD                                                                                               
SAN & STTR Research Program Administrator

5:15 - 6:30 pm

10-Year Celebration Reception 

Help us celebrate 10 years of STTR! 

Winners of the poster session will be announced!

1 - Alexis Taber

TGF-β Reprograms Memory CD8 T Cells Leading to Altered Function and Chemotaxis Following Reactivation 

Transforming growth factor β (TGF-β) directly acts on T cells during priming to control subsequent cell fate decisions. However, the consequences of TGF-β signals for memory CD8 T cell reactivation remain poorly understood. We aim to characterize the temporal effects of TGF-β on reactivated memory CD8 T cells as well as epigenetic and transcriptional changes. We performed ex-vivo stimulation assays on T cells isolated from OT-1 memory mice and analyzed protein expression via flow cytometry. Gene expression changes in memory CD8 T cells linked to TGF-β exposure were further investigated with RNA and ATAC sequencing.

2 - Ashmithra Rajendran

Decoding Cellular Heterogeneity in Human Embryonic Brain Development with Single Cell Transcriptomics

Normal brain development integrates a synchrony of differentiation, specification, and maturation events that have yet to be entirely understood from a cellular or multi-omic perspective. Tremendous single cell sequencing feats over the past decade began decoding cellular ambiguities involved in developmental neurobiology. However, cellular identification with single cell data proves challenging to do with high certainty, especially while developing cells are in constant flux and transitions during development. In this project, we propose a cell type and state identification method based on cell type associative probabilities, cell state uncertainties, and correlative gene modules. 

3 - Cecilia Yeung, MD

Validation of the NCI Genexus Myeloid Assay for Myelomatch

The NCI MyeloMATCH is an innovative and novel precision medicine clinical trial with the goal of getting targeted novel treatments to patients with AML to improve overall survival. This study aims to evaluate treatments for participants at the time of initial acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) diagnosis based on genomic profile. In concert with the NCI Molecular Characterization laboratory (MoCha), we report the validation of rapid genomic profiling assay, NCI myeloid assay (NMA), that uses Oncomine Myeloid Assay GX v2 on the novel Ion Torrent Genexus System developed by ThermoFisher Scientific which is a fully automated platform with a turnaround time of <48 hours from specimen receipt to clinical reporting.

4 - Elizabeth Bonner

As human life spans increase so does the need for therapies to treat age-related diseases such as myelodysplastic syndromes (MDS). The most common gene mutation found in MDS patients is SF3B1, a component of the spliceosome. Mechanistically, SF3B1 mutations cause global splicing changes resulting in the production of abnormally processed mRNA species through either RNA isoform stabilization or degradation. How and if these aberrant transcripts directly cause MDS still remains unclear and is the focus of intense research in the field. Yet, despite decades of effort, no validations studies yet exist that link splicing mutations to abnormal hematopoiesis, the cardinal feature of MDS. I hypothesize that SF3B1 mutations drive dysplastic hematopoiesis by disrupting transcriptional networks responsible for lineage commitment. I have identified CDK8, a member of the mediator kinase module, as one potential mechanism by which SF3B1 mutations drive hematopoietic dysplasia. My preliminary data suggests that CDK8 inhibits hematopoietic output in vitro. 

5 - Emily Liang, MD

Phase 1/2 Clinical Trial of CD19 Chimeric Antigen Receptor T-cell Therapy for Relapsed/Refractory Chronic Lymphocytic Leukemia: 6-year Follow-up

CD19-targeted chimeric antigen receptor-modified (CD19 CAR) T-cell therapy is transforming the treatment landscape of relapsed/refractory (R/R) B cell malignancies. We have reported high efficacy in patients (pts) with high-risk R/R chronic lymphocytic leukemia (CLL) treated on a phase I/II clinical trial with a defined-composition (1:1 ratio of CD8+:CD4+) CD19 CAR T-cell product containing a 4-1BB costimulatory domain (NCT01865617; Turtle, JCO 2017). However, long-term outcomes and the factors associated with duration of response (DOR) after CD19 CAR T-cell therapy for R/R CLL are not well characterized. We report comprehensive analyses of factors associated with duration of response (DOR) with over 6 years of median follow-up.

6 - Emma Wrenn, PHD

Cancer-associated Fibroblast-like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment via ECM Deposition

Ewing sarcoma (EwS) cells exist along a neuro-mesenchymal transcriptional continuum that is largely determined by transcriptional activity of the EWS::FLI1 fusion oncoprotein. Although EWS::FLI1-low state cells are more metastatic in experimental models, the role of these cells in established EwS tumor ecosystems is unknown. Here we have leveraged multimodal single-cell sequencing, spatial transcriptomics, and immunohistochemical profiling to characterize EwS cell subpopulations in cell lines, PDX models, and patient tumors. We identify CD73 as a marker of mesenchymal-high state EwS cells and show that CD73+ tumor cells share properties of experimentally-induced EWS::FLI1-low cells including altered cytoskeletons, enhanced migration and invasion, and increased expression of EWS::FLI1-repressed genes.

7 - Fan Zhang, PHD

The Roles of Informatics and AI in Current and Future States Managing Incidentalomas in Radiology 

Increasing use of diagnostic imaging has led to a rise in the incidence of unexpected findings discovered during unrelated imaging studies, or incidentalomas. The discovery of incidentalomas may facilitate earlier diagnosis and treatment of cancers. However, unnecessary and/or invasive procedures in follow-up care may cause avoidable harm. Currently, there is a lack of standardization for managing incidentalomas, which imposes risks of overdiagnosis or underdiagnosis on patients. A more effective process for reporting, tracking, and determining clinical outcomes is a complex task that requires enhancements in current informatics structures. We are building a framework for understanding the current and potential future states for managing incidentalomas in radiology, and the downstream effects. 

8 - Jodiene Johnson

Decoding the Mechanism for Retinoblastoma Protein-dependent Nuclear Envelope Rupture

The nuclear envelope is a physical barrier that compartmentalizes and protects the genome. Structural components of the nuclear envelope include the nuclear lamina, a meshwork of intermediate filaments, and lamina-associated heterochromatin domains (LADs), which regulate nuclear response signaling and mechanical resistance to force. Perturbations of these structural components can destabilize the nuclear envelope and cause nuclear envelope rupture in response to mechanical stress. Ruptures commonly occur in migrating cancer cells and cells with nuclear lamina protein mutations, causing DNA damage, genome instability, and cellular invasion. We recently validated that depletion of the tumor suppressor protein retinoblastoma (RB) causes a substantial increase in nuclear envelope rupture in multiple types of non-transformed cells. 

9 - Katelyn Costanza

Survival and Clinical Characteristics of Patients with Glioblastoma with Primitive Neuronal Component

A subset of malignant gliomas are found to have solid-looking primitive nodules which confer a diagnosis of glioblastoma with primitive neuronal component (GBM-PNC). At initial diagnosis, GBM-PNC is associated with increased responsiveness to platinum-based therapies and high rates of cerebrospinal fluid dissemination. It is unknown if the same characteristics and risks exist when primitive neuronal component develops at recurrence after an initial diagnosis with a malignant glioma. The University of Washington pathology database was queried between the years of 2005 to 2021 to identify patients with a pathological diagnosis of GBM-PNC. Clinical and radiographic data were abstracted. Descriptive statistics and survival analysis were performed.

10 - Kevin Tatunay

Paired Genetic Testing for Esophageal and/or Gastric Cancer Increases Access to Targeted Therapy 

Patients with a hereditary cancer syndrome (HCS) have a strong response to immune checkpoint inhibitors (ICIs). This has led to an increase in use of genetic testing for lower GI cancer treatment decisions. Ease and cost-effectiveness of using multiplex next generation sequencing assays has helped identify individuals carrying a HCS at diagnosis of cancer even when they had an atypical, an unknown, or no family history, making them and their at-risk family members eligible for lifesaving screening and preventative interventions. Coverage for genetic testing for patients with upper GI cancers is denied by most insurances. We planned to enroll 50 patient with gastroesophageal cancer (GEC) and offer them paired Oncoplex and BROCA genetic test from the University of Washington. 

11 - Liberalis Boila, PHD

Cholangiocarcinoma (CCA) is the second most common primary hepatic malignancy. Intrahepatic cholangiocarcinoma (ICC) accountS for 10-20% of all CCA. Over the last four decades, the reported age-standardized incidence for ICC has been steadily increasing in most locations worldwide. Multiple sequencing studies have identified recurrent mutations in patients presenting with ICC, with IDH1 and ARID1A being the top two mutated genes. While IDH1 mutation has been shown to induce a differentiation block the role of ARID1A in ICC remains to be explored. ARID1A is one of the defining subunits of the mammalian canonical BAF (c-BAF) complex. Inactivating mutations in ARID1A have been described in a wide variety of cancers. Analysis of the MSK ICC cohort reveals >85% of mutations to be truncating mutations. Analysis of an independent ICC cohort indicated poorer overall and disease-free survival for patients harboring ARID1A mutations. Our lab has successfully developed a novel GEMM by combining liver-specific knockout of Arid1a using Alb-Cre recombinase with oncogenic KrasG12D. 

12 - Lindsay Dickerson, MD

Therapeutic Modulation of Tumor-infiltrating T Cell Function in Fibrolamellar Carcinoma (FLC)

Fibrolamellar carcinoma (FLC), a rare liver cancer affecting young patients without cirrhosis, has a poor prognosis and few systemic therapy options. Current evidence implicates an immunosuppressive tumor microenvironment (TME), including sequestration of tumor-infiltrating lymphocytes (TILs) and impaired cytotoxic T cell activity. We hypothesized that combination blockade of C-X-C chemokine receptor type 4 (CXCR4) and programmed cell death protein (PD-1) would enhance T cell infiltration and activation, respectively, and thereby increase tumor killing. Patient-derived FLC and matched non-tumor liver (NTL) specimens were analyzed with flow cytometry to characterize baseline T cell phenotype. Tumor slice cultures (TSCs) from five patients were treated with IgG1 isotype control, AMD3100 (AMD, a small molecule inhibitor of CXCR4), and anti-PD-1

13 - Meiling Liu

TCR-L: An Analysis Tool for Evaluating the Association Between the T-cell Receptor Repertoire and Clinical Phenotypes

T cell receptors (TCRs) play critical roles in adaptive immune responses, and recent advances in genome technology have made it possible to examine the T cell receptor (TCR) repertoire at the individual sequence level. The analysis of the TCR repertoire with respect to clinical phenotypes can yield novel insights into the etiology and progression of immune-mediated diseases. However, methods for association analysis of the TCR repertoire have not been well developed. We introduce an analysis tool, TCR-L, for evaluating the association between the TCR repertoire and disease outcomes. Our approach is developed under a mixed effect modeling, where the fixed effect represents features that can be explicitly extracted from TCR sequences while the random effect represents features that are hidden in TCR sequences and are difficult to be extracted.

14 - Mohamed Adil

Molecular Phenotype Classification of Metastatic Prostate Cancer by Cell-free DNA Methylation Analysis 

Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease which can be classified into clinically relevant subtypes based on the expression of transcription factors (TF). Neuroendocrine prostate cancer (NEPC), characterized by gain of stem-like and neuroendocrine features and lack of AR expression is a clinically aggressive variant. Due to the absence of adequate biomarkers, NEPC is usually detected at a very advanced stage. There is mounting evidence that molecular subtype changes seen in NEPC are enforced by widespread epigenetic alterations, in particular DNA methylation changes. In this study, we aim to devise a novel DNA methylation-based assay for molecular subtyping and disease monitoring from cell-free DNA (cfDNA). We analyzed genome wide methylation patterns in 60 prostate cancer patient-derived xenograft (PDX) and 133 mCRPC tumors using array- and sequencing-based assays.

15 - Naomi Yamamoto

Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest cancers in the United States with a five-year survival rate of 11.5%, primarily due to a lack of effective screening, prevention, and targeted treatment methods. Transcriptional profiling studies over the last decade have defined a more aggressive basal/quasi-mesenchymal disease subtype, associated with more aggressive disease and a poorer prognosis than the classical subtype. Treatments targeting these disease subtypes have the potential to substantially improve patient care. We have implicated the oncofetal protein LIN28B as a marker of the basal subtype and have found that it may play a role in suppressing the innate immune response. Chromatin-bound LIN28B plays a role in suppressing cellular RNA:DNA hybrids that form during active transcription (R-loops), which may drive transcriptional alterations in basal subtype pancreatic cancer cells. Our preliminary results implicate that LIN28B expression downregulates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis. 

16 - Olga Sala-Torra

Detection of Gene Fusions in Leukemia Using Nanopore Long Read Sequencing

Nanopore is a long-read sequencing platform that decodes nucleotide sequences from changes in electric current induced by nucleic acid translocating through a biologic pore. The latest iteration of the nanopore chemistry achieves over 99% accuracy, which along with the lack of capital investment needed and the possibility of real-time analysis makes this platform very attractive as a point-of-care device in underserved communities. We have developed an amplification-free assay that utilizes CRISPR-Cas9 to enrich for specific regions of interest and sequence using Nanopore. In this assay we target simultaneously regions involved in different recurrent fusions in myeloid malignancies: BCR::ABL1, PML::RARA, CBFB::MYH11, KMT2A:: AFF. Additionally we modified Bwb, a graphical tool to create and execute bioinformatic workflows, for nanopore data analysis. 

17 - Pushpa Itagi, PHD

Elucidating Tumor Evolution and Heterogeneity in Advanced Bladder Cancer from Rapid Autopsies 

Bladder Cancer is a highly prevalent cancer with staggering mortality of about 20%. Metastatic BLCA (mBLCA) with variant histologies are aggressive and have a poor prognosis. The extent and impact of tumor heterogeneity in these variants are not fully understood. In this work, we aim to characterize intra-patient and inter-patient tumor heterogeneity from genomic and transcriptomic analysis from a rapid autopsy cohort of 20 patients; this novel work will provide us with unique insights into heterogeneity and clonal evolution in mBLCA. For this, we are investigating the genomic features and signatures for single nucleotide variants, copy number alterations, and structural variants. Using the estimated cellular prevalence, we elucidate the clonal dynamics of each patient and then infer the clonality signatures that occur in the different tumors.  

18 - Rasika Venkataraman

Investigation of the Role of RNA Helicase DDX41 in the Pathogenesis of MDS/AML 

Germline mutations in the RNA helicase DDX41 are the most common genetic predisposition to MDS and AML. Patients with germline heterozygous mutations in DDX41 present with clinical symptoms at a median age of 70 years, similar to de novo disease. ~70% of patients with germline DDX41 mutation acquire a somatic missense mutation in the helicase domain of the healthy allele (p.R525H) leading to secondary AML. While recent studies have highlighted the role of DDX41 mutations in hematopoietic cell dysfunction, snoRNA processing, ribosome biogenesis, R- loop resolution and inflammation, the precise mechanisms by which these mutations drive disease is poorly understood. WE used AML cell lines K562 and MOLM-13, human cord blood CD34+ cells and lentivirus expressing shRNA targeting DDX41 or overexpressing cDNA coding for

19 - Ridvan Demirci, MD

Post-treatment PSMA SPECT/CT in the Monitoring of Response in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Lu-177-PSMA and Correlation Between Quantitative Imaging and Biochemical Biomarkers: Preliminary Results

Lu-177-PSMA is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer by delivering beta radiation to tumor tissues expressing PSMA and limited radiation to normal organs. Concurrent gamma radiation from Lu-177 decay allows for whole-body imaging by SPECT/CT that has shown promising results in verifying and quantifying Lu-177 PSMA delivery to target tissues. Here, we sought to evaluate the relationship of quantitative SPECT/CT parameters and clinical outcomes for patients treated with Lu-177 PSMA. A total of 64 patients who have been treated with Lu-177 PSMA in our center, and who had undergone at least two cycles of treatment, were included in the analysis. Whole-body tumor segmentation was performed semiautomatically. 

20 - Ryma Toumi, PHD

Overcoming barriers to T cell therapy against Acute myeloid leukemia with Dual Costimulatory Receptors

Pediatric AML is one of the most common cancers diagnosed in children and adolescents and the second leading cause of cancer deaths among this age group. Despite improvements in AML treatment, many patients develop relapsed and refractory disease, highlighting an urgent need to develop more innovative therapies. Adoptive cell transfer (ACT) with T-cell receptor-engineered T cells (TCR-T cells) involves generating and modifying targeted T cells to recognize tumor cells with high specificity and efficiency. TCR-T cells are independent of the patient's endogenous T cell pool and constitute a 'living drug' that helps orchestrate an immune response against AML. Despite the remarkable clinical benefits observed with TCR-T cells, efforts are required to improve their persistence and antitumor functions in vivo. AML blasts produce several immunosuppressive molecules and display several metabolic alterations facilitating their escape from immune surveillance.

21 - Sayantani Sinha, PHD

Targeting Splicing Factor Mutations via PARP1 Inhibition

Somatic mutations affecting splicing factor (SF) genes SRSF2, SF3B1 and U2AF1 are found across a spectrum of clonal myeloid diseases including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Previous studies found an abundance of unscheduled RNA:DNA hybrid (R-loop) formation in SF mutant cells and associated genomic instability that could be targeted using ATR kinase inhibitors. We hypothesize that therapeutic targeting of R-loop-associated pathways and/or DNA damage response (DDR) pathways represent a novel therapeutic strategy against SF mutant cancers. Using isogenic murine leukemia cells on an Srsf2 mutant background, we performed a small drug screen. We found that the presence of  SF mutations (SRFS2 P95H and U2AF1 S34F) conferred enhanced sensitivity to FDA-approved PARP inhibitors (PARPi). 

22 - Shruthi Kondaboina, Eric Lassiter, Hafsa Masude

Intracranial Epidermoid Cysts (IECs) are benign slow-growing tumors located in the parasellar region and cerebellopontine angle of the brain. Since they are slow-growing and asymptomatic, these tumors are significantly enlarged when discovered. The enlarged mass leads to trigeminal neuralgia, visual and hearing loss, tinnitus, severe face pain, and seizures. It is suspected that IECs are formed as a result of a disruption during neural tube closure in embryogenesis. Due to their rarity, IEC are poorly investigated, and the complex mechanisms of IEC formation and progression remain unknown. Consequently, there is no drug therapy available to date. Surgery is still the only effective treatment option. Surgical complications include deafness, facial weakness and chemical meningitis due to the post-surgical inflammation of the meninges. These observations highlight the need to investigate the pathogenesis of IECs to develop additional targeted therapeutic options for these patients. We have performed paired-end Whole Exome Sequencing (WES) on DNA isolated from IECs resected from six patients. 

CARIS 

Caris has been the leading innovator in molecular profiling since we were first founded in 2008. With the promise of precision medicine becoming a reality, broad molecular profiling has become standard of care for many cancer types – and is required for certain therapies. More than ever, oncologists need a trusted profiling partner to provide reliable, high-quality molecular profiling information to guide precise and individualized treatment decisions. Their comprehensive molecular profiling approach precisely analyzes DNA, RNA, and protein biomarkers, revealing the highest quality molecular blueprint for evidence-based selection of the most appropriate cancer therapy. In addition to comprehensive molecular profiling, Caris has innovated industry-leading artificial intelligence algorithms that predict patient responses to standard treatments, such as immunotherapy or chemotherapy, based on their personalized molecular profile. Caris is the original, most experienced comprehensive molecular profiling laboratory, and they have optimized their systems to provide industry-leading reports, service and turnaround time.

Foundation Medicine

Foundation Meidicne is an essential partner to patients, physicians, researchers, and biopharma organizations navigating the complex landscape of cancer care. Their genomic insights help guide informed decisions about treatment plans and research priorities. Over the past decade, they’ve partnered with researchers, biopharma, advocacy organizations, government bodies, health plans, and regulators to validate the use of genomic testing in clinical care, drive awareness among patients and physicians and ultimately support broader access for patients. The answers they provide through their testing are essential first steps in developing informed treatment strategies and accelerating the development of transformative new therapies.

Illumina

Illumina's mission is to improve human health by unlocking the power of the genome. They believe that, together, they can use genomics to build a stronger world for the greater good.

Tempus

Tempus delivers a broad range of sequencing services—tumor tissue and liquid DNA profiling, somatic and germline testing, tumor-normal matched profiling and RNA sequencing—all of which empowers you to make data-driven decisions for your patients. Tempus provides integrated solutions to help meet your needs from early discovery through commercialization. Advance discovery, innovation, and increase the likelihood of trial success with real-world clinical and molecular data, including DNA, RNA and whole slide pathology images.

Cleavon Joseph 

OpenSpecimen: Specimen Data Management Tool

The Specimen Data Management Tool (OpenSpecimen) is a Consortium-wide solution to support and enhance the management of specimen-associated data. OpenSpecimen is a highly configurable web-based Biobanking Laboratory Information Management System (LIMS) used in 70+ clinical research centers across 20+ countries - including many of the world’s leading research centers. OpenSpecimen helps you collect High-quality Biospecimen Data and track biospecimens from Collection to Utilization. 

To view a PDF document with the Open Specimen features, click here

To view a short video of the Open Specimen features, click here

Matt Jensen

Oncoscape

Ask us about: Benefits of Oncoscape / Training / Accessing Shared Datasets / Uploading Your Own Datasets / Desired Functionality and Improvements​

Snehal Joshi, PHD

Specimen and Data Acquisition Network

Ask us about: Accessing human-derived specimens and associated datasets, research connection and resource management  ​

Kara Colevas & Monica Gerber, MPH

Clinical Data Requests

What we do: A partnership between OTR and the Data Science Lab (DaSL) to oversee the clinical data request process. We review and triage data requests, deliver approved datasets per investigator needs, and strive to improve data accessibility.

Ask us about: How to submit a data request, What is required to ask for a data export, The types of data available

clin_dataserv_req@fredhutch.org

https://extranet.fredhutch.org/en/u/consortium-clinical-data-access.html

https://hutchdatascience.org/contact/

Alex Zevin, PHD

Genomics Shared Resource

Amanda Koehne, DVM, PHD, DACVP

Translational Pathology

Angela Bryce

Research Cell Bank

We provide tissue culture (transformation/expansion), nucleic acid extraction, and biorepository services.

Ask us about:

• DNA & RNA extraction
• Blood processing and PBMC isolation
• BioBanking and cryopreservation
• Mycoplasma testing

Daniel Schullery

Specimen Processing

What we do: We provide biospecimen sample processing, banking, and shipping services.

Ask us about:

• Processing of Clinical Research Specimens
• Blood, tissue, urine, stool, etc.
• Shipping to collaborators and central labs

Jianhong Cao, PHD

Immune Monitoring Lab

Priti Singh, PHD & Elizabeth Cromwell

Preclinical Modeling Shared Resource

Facilitates the in vivo preclinical discovery platforms via development and maintenance of the novel preclinical mouse models. This program integrates the mouse Patient derived xenograft (PDX) program and genetically engineered mouse modeling (GEMM) program to bring a major boost to the mouse cancer research at Fred Hutch.

PDX: Custom Patient Derived Xenograft (PDX) model development; Cell-line-derived xenograft (CDX); Orthotopic/Heterotopic tumor model; Preclinical Treatment Studies; Expert study design and consultation; PDX Tumor Bank house over 100 PDX models

GEMM: CRISPR-Mediated Gene Targeting in Mice; One-cell embryo pronuclear microinjection; ES cell microinjection Mouse sperm/embryo cryopreservation; Mouse sperm/embryo resuscitation; Speed expansion to generate age-matched mouse colony