William G. Kaelin Jr.
威廉·卡林
MD
Professor of Medicine; Investigator, Howard Hughes Medical Institute医学教授；霍华德·休斯医学研究所研究员
👥Biography 个人简介
William G. Kaelin Jr., MD is a Nobel Prize-winning scientist whose elucidation of the VHL-HIF oxygen-sensing pathway provided the molecular foundation for targeted therapies in clear cell RCC, including VEGFR inhibitors and the HIF-2α inhibitor belzutifan. His work at Dana-Farber and HHMI defining how VHL regulates HIF-α subunit stability under normoxic conditions is among the most impactful discoveries in cancer biology of the past three decades.
🧪Research Fields 研究领域
🎓Key Contributions 主要贡献
Elucidation of the VHL-HIF Oxygen-Sensing Pathway
Discovered the molecular mechanism by which the VHL tumor suppressor protein targets HIF-α subunits for proteasomal degradation under normoxia, establishing the biochemical basis for hypoxia signaling in clear cell RCC and earning the 2019 Nobel Prize in Physiology or Medicine.
Rationale for HIF-2α Inhibition in RCC
Identified HIF-2α as the principal oncogenic driver downstream of VHL loss in clear cell RCC, providing the scientific rationale for developing HIF-2α inhibitors such as belzutifan as targeted therapies for this disease.
Synthetic Lethality Concepts in VHL-Deficient RCC
Pioneered systematic RNAi and CRISPR screens to identify synthetic lethal interactions with VHL loss in clear cell RCC, revealing novel therapeutic vulnerabilities including CDK4/6, PARP, and metabolic targets.
Prolyl Hydroxylase as Oxygen Sensor
Demonstrated that prolyl hydroxylase domain proteins (PHDs) act as the cellular oxygen sensors that modify HIF-α for VHL recognition, a fundamental mechanistic insight with broad implications for ischemia, anemia, and cancer biology.
Representative Works 代表性著作
Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase Pathway
Molecular Cell (2008)
Comprehensive review of the VHL-PHD-HIF axis establishing the molecular mechanism of oxygen sensing and its dysregulation in clear cell RCC and other VHL-associated tumors.
Molecular Basis of the VHL Hereditary Cancer Syndrome
Nature Reviews Cancer (2002)
Seminal review detailing how VHL loss drives HIF accumulation and downstream oncogenic programs including VEGF upregulation, laying groundwork for VEGFR-targeted therapy in RCC.
Targeting HIF-2: Therapeutic Perspectives for Clear Cell Renal Cell Carcinoma
Cancer Discovery (2020)
Reviewed preclinical and early clinical evidence for HIF-2α inhibition in VHL-mutant clear cell RCC, providing mechanistic context for belzutifan development.
🏆Awards & Recognition 奖项与荣誉
📄Data Sources 数据来源
Last updated: 2026-01-15 | All information from publicly available academic sources
Related Experts 相关专家
Bing Ren
University of California San Diego, Ludwig Cancer Research
Cigall Kadoch
Dana-Farber Cancer Institute / Broad Institute of MIT and Harvard
Luciano Di Croce
Centre for Genomic Regulation (CRG), Barcelona
Alexander Meissner
Max Planck Institute for Molecular Genetics, Berlin
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