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Donald McDonnell, PhD

Professor
Duke University School of Medicine
Durham, NC, United States

Donald McDonnell, PhD, Glaxo Welcome Professor of Molecular Cancer Biology in the Department of Pharmacology and Cancer Biology (Duke University School of Medicine).

Dr. McDonnell is a translational scientist who employs genetics, biochemistry, and chemical biology to probe the molecular mechanisms underlying the pathobiology of dysregulated hormone signaling in different cancers. His work established the concept of “functional allostery” in nuclear/steroid receptor signaling demonstrating that ligand structure influences receptor conformation to facilitate differential recruitment of accessory proteins to effect different biological responses. Leveraging this information his group discovered a new class of medicines (oral Selective Estrogen Receptor Downregulators; SERDs), several of which are approved/in clinical trials. Notable was his group’s discovery of Elacestrant (FDA approved January 2023) and Lasofoxifene (Phase III) as treatments for metastatic breast cancer. Exploiting the concept of functional allostery they have developed new approaches to target the androgen signaling axis in metastatic castrate resistant prostate cancer and drugs emerging from this endeavor are moving towards the clinic. In recent years, his group has embarked on a major effort to understand how sex hormones impact tumor immunity through their ability to regulate immune cell repertoire and function. The clinical translation of insights from this work is a current focus of the group’s efforts. Dr. McDonnell and his team have also had a longstanding interest in defining the mechanisms by which hypercholesterolemia and dyslipidemia impact cancer biology and have defined the mechanisms by which specific cholesterol metabolites facilitate metastatic progression in breast cancer. Dr. McDonnell is a recipient of a DOD Breast Cancer Innovator Award, The Baxter prize, and is a Komen Scholar. He is a Member of the National Academy of Medicine (NAM), the National Academy of Inventors (NAI), the Royal Irish Academy (RIA) and the Royal College of Physicians Ireland (RCPI)

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