Prof. dr. Donald McDonnell

Duke University, North Carolina, USA

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 currently 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. This research has been funded continuously for 33 years by the NCI/NIH, the Prostate Cancer Foundation, the Komen Foundation, the Melanoma Research Foundation, and the Department of Defense. Dr. McDonnell is a recipient of a DOD Breast Cancer Innovator Award and is a Komen Scholar. He is a Member of the National Academy of Medicine and the National Academy of Inventors.