Owen Witte

About

Owen Witte received his undergraduate degree from Cornell University and his MD from Stanford University. He completed postdoctoral research at MIT and subsequently joined the faculty at UCLA, where he is currently a University Professor of Microbiology, Immunology, and Molecular Genetics, holding the President’s Chair in Developmental Immunology. He is also the Director Emeritus of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. Dr. Witte has made significant contributions to the understanding of human leukemias, immune disorders, and epithelial cancer stem cells. His work includes the discovery of tyrosine kinase activity for the ABL gene and the demonstration of the BCR-ABL oncoproteins in human leukemias, which has led to the development of kinase-targeted therapies for these cancers. Additionally, he co-discovered Bruton’s tyrosine kinase (BTK), essential for normal B-lymphocyte development, with mutations leading to X-linked agammaglobulinemia, an immune deficiency. New inhibitors for BTK are now entering clinical practice for certain lymphomas and leukemias. His recent research focuses on defining stem cells and growth regulatory pathways for epithelial cancers, particularly prostate and other organ sites, to develop new therapies. His group also investigates mechanisms of therapy resistance in cancers driven by epigenetic changes, especially the conversion of aggressive adenocarcinomas to small cell neuroendocrine phenotypes,…

Research topics

• Biology
• Cancer research
• Medicine
• Oncology
• Genetics
• Bioinformatics
• Immunology
• Cell biology
• Internal medicine

Selected publications

• The DNA methylation landscape of advanced prostate cancer

  Nature Genetics · 2020 · 348 citations

  DOI

• Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance

  Proceedings of the National Academy of Sciences · 2020 · 168 citations

  gene alterations and AR expression were similar between groups. Importantly, however, transcriptional measurements demonstrated that specific gene sets-including those linked to low AR transcriptional activity and a stemness program-were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance.

  DOI

• Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy

  Cell Reports Medicine · 2021 · 101 citations

  HSC-iNKT cell products and lay a foundation for their translational and clinical development.

  DOI

• Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity

  Nature Communications · 2022 · 59 citations

  The androgen receptor (AR) signaling inhibitor enzalutamide (enza) is one of the principal treatments for metastatic castration-resistant prostate cancer (CRPC). Several emergent enza clinical resistance mechanisms have been described, including lineage plasticity in which the tumors manifest reduced dependency on the AR. To improve our understanding of enza resistance, herein we analyze the transcriptomes of matched biopsies from men with metastatic CRPC obtained prior to treatment and at progr…

  DOI

• PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity

  Proceedings of the National Academy of Sciences · 2024-11-26 · 13 citations

  articleOpen accessSenior authorCorresponding

  Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers composed of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of proliferator-activatedreceptor gamma coactivator 1-alpha (PGC-1α), a potent regulator of mitochondrial oxida…

  PublisherOA PDFDOI

Recent grants

• NIH Grant P01CA012800

  NIH · $10.5M · 2000

• UCLA-Caltech Medical Scientist Training Program

  NIH · $35.5M · 1983–2024

• NIH Grant U54CA119347

  NIH · $24.4M · 2010

Frequent coauthors

• Antoni Ribas

  Parker Institute for Cancer Immunotherapy

  253 shared

• Donghui Cheng

  Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

  211 shared

• Caius G. Radu

  University of the Witwatersrand

  161 shared

• Jiaoti Huang

  Duke University

  158 shared

• David Baltimore

  152 shared

• James R. Heath

  Institute for Systems Biology

  136 shared

• Jami McLaughlin

  University of California, Los Angeles

  120 shared

• Sanaz Memarzadeh

  University of California, Los Angeles

  116 shared

Education

• M.D.

  Stanford University

  1976

• B.S.

  Cornell University

  1971

Awards & honors

• Association of American Medical Colleges' Award for Distingu…
• Arthur Kornberg and Paul Berg Lifetime Achievement Award in…

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