About
Titles
Assistant Professor
Biography
Dr. William Kim has demonstrated a passion for interdisciplinary collaboration. His research leverages advanced computational and data-driven approaches alongside genome engineering technologies to contribute to advancing our understanding of cancer. Kim received his PhD from Duke University and the Institute for Genome Sciences Policy, where he received support from the Department of Defense Breast Cancer Research Predoctoral Program and the Korean Science & Engineering Foundation Award.
Following his doctoral work, Kim joined the Dana Farber Cancer Institute and the Broad Institute of Harvard and MIT for his postdoctoral research. There, he made significant contributions to developing novel computational approaches for the systematic characterization of cancer genomes and oncogenic cellular states. He also discovered a novel role for the Protein phosphatase 2A (PP2A) enzyme in oncogenic transformation, expanding the understanding of this important signaling pathway.
Leveraging his expertise in cancer biology and computational biology, Kim then joined the University of California San Diego (UCSD) School of Medicine in the Division of Genomics and Precision Medicine. At UCSD, he co-led a multidisciplinary team of researchers, clinicians, patients, and community advocates on a California Initiative for Precision Medicine Project, supported by the California Governor's Office. Kim also served as the Co-Director of the UCSD Center for Cancer Target Discovery and Development (CTD2), further driving the integration of data-driven and biological approaches to cancer research.
William Kim joined the Department of Urology at Yale University School of Medicine. Here, he aims to bridge the gap between cancer biology and data science, working towards a comprehensive understanding of cellular circuitry and the realization of the full potential of cancer precision medicine.
Appointments
Urology
Assistant ProfessorPrimary
Other Departments & Organizations
- Genomics, Genetics, and Epigenetics
- Urology
- Yale Cancer Center
Research
Overview
The Kim lab employs systematic approaches to study cancer, with the goal of discovering the most effective strategies for prevention and treatment. Our methodology involves 1) comprehensive assessment of oncogenic programs in cancers using integrated machine-learning techniques, 2) deep interrogation of molecular changes in response to pharmacological and genetic perturbations, and 3) reconstruction and reverse engineering of cancer cells to create better models of the disease. These approaches will enhance our understanding of cancer as a complex system, ultimately guiding the development of strategies that maximize therapeutic efficacy while minimizing drug resistance and disease recurrence in patients.
Medical Research Interests
Biomarkers, Tumor; Cell Division; Cell Transformation, Neoplastic; Cellular Reprogramming; Computational Biology; Gene Expression; Health Inequities; Machine Learning; Multiomics; Neoplasms; Oncogene Addiction; Precision Medicine; Translational Science, Biomedical
Public Health Interests
Genetics, Genomics, Epigenetics; Cancer; Community Engagement; Network Analysis
ORCID
0000-0002-3021-7193
Research at a Glance
Research Interests
Research topics William J. Kim is interested in exploring.
Neoplasms
Biomarkers, Tumor
Computational Biology
Cell Transformation, Neoplastic
Precision Medicine
Publications
2024
Targeting TREX1 induces innate immune response in drug-resistant Small Cell Lung Cancer.
Murayama T, Mahadevan NR, Meador CB, Ivanova EV, Pan Y, Knelson EH, Tani T, Nakayama J, Ma X, Thai TC, Hung YP, Kim W, Watanabe H, Cai K, Hata AN, Paweletz CP, Barbie DA, Canadas I. Targeting TREX1 induces innate immune response in drug-resistant Small Cell Lung Cancer. Cancer Res Commun 2024 PMID: 39177280, DOI: 10.1158/2767-9764.CRC-24-0360.Peer-Reviewed Original ResearchTargeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer
Murayama T, Nakayama J, Jiang X, Miyata K, Morris A, Cai K, Prasad R, Ma X, Efimov A, Belani N, Gerstein E, Tan Y, Zhou Y, Kim W, Maruyama R, Campbell K, Chen L, Yang Y, Balachandran S, Canadas I. Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer. Cancer Discovery 2024, 14: 468-491. PMID: 38189443, PMCID: PMC10905673, DOI: 10.1158/2159-8290.cd-23-0486.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSmall cell lung cancerDExD/H-box helicase 9Cell lung cancerCold tumorsLung cancerResponse to immune-checkpoint blockadeInnate immunityEnhance immunotherapy efficacyImmune-checkpoint blockadeImmunogenic tumor microenvironmentImmunologically cold tumorsNucleic acid-sensing pathwaysActivate innate immunityAntitumor immunityImmunotherapy efficacyReplication stressTumor microenvironmentTumor growthViral mimicryTumorImmune responseCancer cellsInterferon responseCytoplasmic dsRNACancer
2023
Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma
Chaudhary P, Xu X, Wang G, Hoj J, Rampersad R, Asselin-Labat M, Ting S, Kim W, Tamayo P, Pendergast A, Onaitis M. Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma. Cancer Research Communications 2023, 3: 2400-2411. PMID: 37882674, PMCID: PMC10668634, DOI: 10.1158/2767-9764.crc-22-0408.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsType II cellsLung adenocarcinomaDual-positive cellsII cellsKRAS-mutant lung adenocarcinomaDevelopment of novel targeted therapeuticsTumor-initiating cellsNotch signalingAlveolar type II cellsNovel targeted therapeuticsCell of originThree-dimensional organoid culturesSOX2 upregulationKRAS activationAdenocarcinomaMouse modelTherapeutic strategiesProliferation of cellsGain-of-functionRNA sequencing analysisTransplantation studiesCellular plasticityOrganoid culturesSOX2 levelsNotch pathwayDeciphering the Functional Roles of Individual Cancer Alleles Across Comprehensive Cancer Genomic Studies.
Ma JY, Ting S, Tam B, Pham T, Reich M, Mesirov J, Tamayo P, Kim W. Deciphering the Functional Roles of Individual Cancer Alleles Across Comprehensive Cancer Genomic Studies. BioRxiv 2023 PMID: 38014215, DOI: 10.1101/2023.11.14.567106.Publications for non-academic audiencesTargeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy
Steen E, Basilaia M, Kim W, Getz T, Gustafson J, Zage P. Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy. Biochemical Pharmacology 2023, 216: 115751. PMID: 37595672, PMCID: PMC10911250, DOI: 10.1016/j.bcp.2023.115751.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsRET inhibitorsRET inhibitionSolid tumorsIncreased RET expressionAssociated with poor prognosisPediatric solid tumorsNeuroblastoma tumor cellsPapillary thyroid cancerTyrosine kinaseOncogenic RET mutationsRET tyrosine kinaseProgression of multiple typesTransmembrane receptor tyrosine kinaseRET mutationsRET expressionReceptor tyrosine kinasesThyroid cancerNeuroblastoma tumorsPoor prognosisPreclinical studiesTumor cellsBreast cancerKinase inhibitorsLung adenocarcinomaClinical trialsTargeting TBK1 to overcome resistance to cancer immunotherapy
Sun Y, Revach O, Anderson S, Kessler E, Wolfe C, Jenney A, Mills C, Robitschek E, Davis T, Kim S, Fu A, Ma X, Gwee J, Tiwari P, Du P, Sindurakar P, Tian J, Mehta A, Schneider A, Yizhak K, Sade-Feldman M, LaSalle T, Sharova T, Xie H, Liu S, Michaud W, Saad-Beretta R, Yates K, Iracheta-Vellve A, Spetz J, Qin X, Sarosiek K, Zhang G, Kim J, Su M, Cicerchia A, Rasmussen M, Klempner S, Juric D, Pai S, Miller D, Giobbie-Hurder A, Chen J, Pelka K, Frederick D, Stinson S, Ivanova E, Aref A, Paweletz C, Barbie D, Sen D, Fisher D, Corcoran R, Hacohen N, Sorger P, Flaherty K, Boland G, Manguso R, Jenkins R. Targeting TBK1 to overcome resistance to cancer immunotherapy. Nature 2023, 615: 158-167. PMID: 36634707, PMCID: PMC10171827, DOI: 10.1038/s41586-023-05704-6.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsOvercome resistance to cancer immunotherapyResistance to cancer immunotherapyPD-1 blockadeCancer immunotherapyImmune-evasion genesResponse to PD-1 blockadePatient-derived tumor modelsPatient-derived organoidsEffective treatment strategiesTBK1 inhibitionPD-1Effector cytokinesConcordant findingsTumor cellsTumor modelCaspase-dependent cell deathResponse to TNFTreatment strategiesTargeting TBK1ImmunotherapyPharmacological toolsBlockadeTumor spheroidsCell deathTBK1
2022
MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer
Yoshida R, Saigi M, Tani T, Springer B, Shibata H, Kitajima S, Mahadevan N, Campisi M, Kim W, Kobayashi Y, Thai T, Haratani K, Yamamoto Y, Sundararaman S, Knelson E, Vajdi A, Canadas I, Uppaluri R, Paweletz C, Miret J, Lizotte P, Gokhale P, Jänne P, Barbie D. MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer. Cancer Research 2022, 82: 4079-4092. PMID: 36066413, PMCID: PMC9627131, DOI: 10.1158/0008-5472.can-22-0770.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsEGFR-mutant lung cancerEGFR-TKI-resistant cellsThird-generation EGFR tyrosine kinase inhibitorMET-amplifiedT cell responsesPemetrexed treatmentLung cancerCD8+ T cell immunogenicityEGFR-TKI treatment failureEGFR tyrosine kinase inhibitorsInhibit T cell responsesUpregulation of CD73Humanized mouse modelTyrosine kinase inhibitorsT-cell immunogenicityCell line studiesMET amplificationEGFR-TKIsTKI resistanceTreatment failureCancer immunogenicityCD73 inhibitionT cellsPemetrexedEnhanced immunogenicityCHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity
Bernareggi D, Xie Q, Prager B, Yun J, Cruz L, Pham T, Kim W, Lee X, Coffey M, Zalfa C, Azmoon P, Zhu H, Tamayo P, Rich J, Kaufman D. CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity. Nature Communications 2022, 13: 1899. PMID: 35393416, PMCID: PMC8990014, DOI: 10.1038/s41467-022-29469-0.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsResistance to NK cell-mediated cytotoxicityHead and neck squamous cell carcinomaNK cell-mediated killingNK cell-mediated cytotoxicityCell-mediated cytotoxicityCell-mediated killingTumor cellsGlioblastoma stem cellsNatural killerNK cellsIncreased NK cell-mediated killingMechanism of tumor immune escapeHead and neck squamous cell carcinoma modelResistance to NK cellsNeck squamous cell carcinomaApoptosis of NK cellsNK cell-mediated immunotherapyExtracellular vesiclesCell-mediated immunotherapyTumor immune escapeImmunodeficient mouse modelSquamous cell carcinomaNK cell migrationIncreased chemokine secretionHuman glioblastoma stem cells
2021
An expanded universe of cancer targets
Hahn W, Bader J, Braun T, Califano A, Clemons P, Druker B, Ewald A, Fu H, Jagu S, Kemp C, Kim W, Kuo C, McManus M, B. Mills G, Mo X, Sahni N, Schreiber S, Talamas J, Tamayo P, Tyner J, Wagner B, Weiss W, Gerhard D, Dancik V, Gill S, Hua B, Sharifnia T, Viswanathan V, Zou Y, Dela Cruz F, Kung A, Stockwell B, Boehm J, Dempster J, Manguso R, Vazquez F, Cooper L, Du Y, Ivanov A, Lonial S, Moreno C, Niu Q, Owonikoko T, Ramalingam S, Reyna M, Zhou W, Grandori C, Shmulevich I, Swisher E, Cai J, Chan I, Dunworth M, Ge Y, Georgess D, Grasset E, Henriet E, Knútsdóttir H, Lerner M, Padmanaban V, Perrone M, Suhail Y, Tsehay Y, Warrier M, Morrow Q, Nechiporuk T, Long N, Saultz J, Kaempf A, Minnier J, Tognon C, Kurtz S, Agarwal A, Brown J, Watanabe-Smith K, Vu T, Jacob T, Yan Y, Robinson B, Lind E, Kosaka Y, Demir E, Estabrook J, Grzadkowski M, Nikolova O, Chen K, Deneen B, Liang H, Bassik M, Bhattacharya A, Brennan K, Curtis C, Gevaert O, Ji H, Karlsson K, Karagyozova K, Lo Y, Liu K, Nakano M, Sathe A, Smith A, Spees K, Wong W, Yuki K, Hangauer M, Kaufman D, Balmain A, Bollam S, Chen W, Fan Q, Kersten K, Krummel M, Li Y, Menard M, Nasholm N, Schmidt C, Serwas N, Yoda H, Ashworth A, Bandyopadhyay S, Bivona T, Eades G, Oberlin S, Tay N, Wang Y, Weissman J. An expanded universe of cancer targets. Cell 2021, 184: 1142-1155. PMID: 33667368, PMCID: PMC8066437, DOI: 10.1016/j.cell.2021.02.020.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNon-oncogene dependenciesDiversity of therapeutic targetsSomatically altered genesCancer targetCancer allelesInfluence therapyCancer genomesGenomic characterizationTherapeutic strategiesAltered genesCancer featuresCancer genesClinical translationCancerCancer biologyTherapeutic targetTumorGenomeGenes
2020
WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer
LEE S, JUN J, KIM W, TAMAYO P, HOWELL S. WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer. Anticancer Research 2020, 40: 6017-6028. PMID: 33109540, PMCID: PMC9312105, DOI: 10.21873/anticanres.14623.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHigh-grade serous ovarian cancerGene set enrichment analysisSerous ovarian cancerWnt signalingOvarian surfaceExpression of RSPO1Gene set enrichment analysis methodRNA-seq dataControl cell fateR-spondinOvarian cancerAnalysis of genesNormal tissuesWnt signaling pathwayHuman Protein AtlasAdjacent genesImpact overall survivalLevel of expressionRNA-seqAssociation studiesCell fateCopy numberGO pathwaysAnalysis of TCGAEnrichment analysis
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