Donald Patrick McDonnell

About

Donald Patrick McDonnell is the Glaxo-Wellcome Distinguished Professor of Molecular Cancer Biology in the School of Medicine at Duke University. He holds multiple positions including Professor of Pharmacology and Cancer Biology, Professor in Medicine, and Professor of Cell Biology. He is also a member of the Duke Cancer Institute. His work is focused on molecular cancer biology, contributing to the understanding of cancer mechanisms and potential therapeutic approaches. As a primary faculty member at Duke, he is actively involved in research and education within the university's biomedical community.

Research topics

• Cancer research
• Genetics
• Endocrinology
• Biology
• Biochemistry
• Chemistry
• Cell biology
• Medicine
• Immunology
• Internal medicine

Selected publications

• Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer

  Nature Communications · 2021 · 333 citations

  Senior authorCorresponding

  Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types and with poor outcomes in patients with established disease. Whereas the mechanisms by which this occurs are multifactorial we determine that chronic exposure of cells to 27-hydroxycholesterol (27HC), an abundant circulating cholesterol metabolite, selects for cells that exhibit increased cellular uptake and/or lipid biosynthesis. These cells exhibit substantially increased tumorigenic and metastati…

  DOI

• Estrogen Receptor Signaling in the Immune System

  Endocrine Reviews · 2022 · 225 citations

  Senior authorCorresponding

  The immune system functions in a sexually dimorphic manner, with females exhibiting more robust immune responses than males. However, how female sex hormones affect immune function in normal homeostasis and in autoimmunity is poorly understood. In this review, we discuss how estrogens affect innate and adaptive immune cell activity and how dysregulation of estrogen signaling underlies the pathobiology of some autoimmune diseases and cancers. The potential roles of the major circulating estrogens…

  DOI

• Targeting androgen receptor signaling to enhance cancer immunotherapy

  Trends in Pharmacological Sciences · 2025-12-01 · 4 citations

  articleOpen access

  Men experience higher cancer incidence and mortality than women, and accumulating evidence implicates androgen receptor (AR) signaling as a key biological driver of these sex-based disparities. AR signaling can suppress adaptive anticancer immunity. Preclinical studies across multiple cancer types show that AR inhibition enhances T cell function and sensitizes tumors to immune checkpoint inhibition. However, recent Phase 3 trials combining AR suppression with immune checkpoint blockade in prosta…

  PublisherDOI

• The Selective Estrogen Receptor Degrader ZN-c5 Has Broad Antitumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models

  Molecular Cancer Therapeutics · 2025-12-11 · 1 citations

  articleOpen access

  Endocrine therapy has proven to be beneficial for patients with estrogen receptor (ER)-positive, HER2-negative (ER+/HER2-) breast cancer; however, de novo or acquired resistance remains a major clinical challenge. Upon progression, many of the cancers continue to be ER dependent, highlighting the opportunities for novel ER-targeting therapies. Fulvestrant, a selective ER degrader (SERD) that antagonizes and degrades ER simultaneously, has demonstrated activity in ER+/HER2- breast cancers the abi…

  PublisherOA PDFDOI

• Data from Discovery of BMS-986365, a First-in-Class Dual Androgen Receptor Ligand-Directed Degrader and Antagonist, for the Treatment of Advanced Prostate Cancer

  2026-01-06

  articleOpen access

  <div>AbstractPurpose:<p>BMS-986365, a heterobifunctional androgen receptor (AR) ligand-directed degrader, was designed as a potent cereblon-dependent degrader and competitive antagonist of the AR to overcome resistance to AR pathway inhibition (ARPI) in metastatic prostate cancer.</p>Experimental Design:<p>The <i>in vitro</i> impact of BMS-986365–induced AR degradation on AR activity and prostate cancer cell proliferation was evaluated. Intrinsic agonistic and…

  PublisherDOI

Recent grants

• The role of ERRalpha/PGC-1 in disease pathogenesis

  NIH · $1.6M · 2006–2018

• NIH Grant R01HD058640

  NIH · $817k · 2011

• NIH Grant R01DK050494

  NIH · $2.5M · 2005

Frequent coauthors

• John D. Norris

  198 shared

• Ching‐yi Chang

  Duke University

  190 shared

• Rachid Safi

  Duke University

  105 shared

• Erik R. Nelson

  University of Illinois Urbana-Champaign

  102 shared

• Suzanne E. Wardell

  Duke University

  100 shared

• Bryan M. Wittmann

  78 shared

• Dmitri Kazmin

  Stanford University

  78 shared

• Mary A. Dwyer

  National Comprehensive Cancer Network

  69 shared

Labs

• McDonnell LabPI

  Our Team Binita Chakraborty, PhD Research Scientist Marina Alorda Clara, PhD Postdoctoral Fellow Jillian Caiazzi Graduate Student Ching-yi Chang, PhD ...

Awards & honors

• Glaxo-Wellcome Distinguished Professor of Molecular Cancer B…

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