JUNE 12, 2025, NEW YORK - Ludwig Cancer Research extends a warm welcome to David MacMillan, who joins our community today as a distinguished scholar at the Princeton Branch of the Ludwig Institute for Cancer Research.
MacMillan, who shared the 2021 Nobel Prize in Chemistry with Benjamin List for their independent development of an entirely novel type of chemical catalysis, is the James S. McDonnell Distinguished University Professor of Chemistry at Princeton University and director of the Princeton Catalysis Initiative, which he founded in 2017.
"We are very excited to have a chemist of such caliber join the Princeton Branch, which is broadly exploring the interplay of metabolism and cancer biology," said Ludwig Institute CEO and Scientific Director Chi Van Dang. "I expect Dave's innovative photo-proximity labeling will be in high demand to de-construct the complexity of the tumor metabolic microenvironment and everything from the microbiome, anti-tumor immune response to cancer metastasis-all of which are areas of intense study across Ludwig Princeton's laboratories."
The distinguished scholar program was created to attract highly accomplished scientists to the Ludwig Institute, and MacMillan certainly fits that bill. His contributions to chemistry have transformed pharmaceutical manufacturing and helped make industrial chemistry both more versatile and environmentally friendly. Materials that accelerate chemical reactions while themselves remaining unchanged, catalysts had long been thought to generally fall into one of only two categories-metals and the enzymes encoded by genes that are indispensable to the chemistry of life. In 2000, MacMillan upended that assumption with the development of asymmetric organocatalysis, in which catalysts are constructed from small organic molecules to which other environmentally benign elements-like oxygen, phosphorus and nitrogen-can be attached for distinct mechanistic purposes.
Chemical reactions can generate products that are identical in every way except that they're mirror images of each other-essentially like our hands. These "chiral" versions of molecules have distinct chemical properties and, often, only one of them has the properties desired. What made MacMillan's catalysts a spectacular success was their utility as drivers of asymmetric chemical reactions that generate primarily one of those mirror images.
The low cost and ease with which these organocatalysts can be rationally designed, made and deployed sequentially to generate complex, symmetrically biased molecules has made them invaluable to industry. They have proved to be of particular utility to pharmaceutical manufacturers, as chirality is a key determinant of the biological activity of drug molecules.
MacMillan is not entirely new to the Princeton Branch. His laboratory has been collaborating with that of Ludwig Princeton Director Joshua Rabinowitz to map molecular interactions associated with the oncogenic signaling of the HER2 protein in malignant cells across different types of breast cancer. Their studies have already uncovered interactions that induce resistance to HER2-inhibiting drugs and might be co-targeted to restore susceptibility to this important family of cancer therapies.
"It's a pleasure working with Dave," said Rabinowitz. "His chemical tools for analyzing, in living systems, biomolecular interactions at atomic resolution are groundbreaking. They are also perfectly poised to address key questions in cancer metabolism and anticancer immunity. We are so excited to have him join the Branch and to collaborate to find new ways to prevent and treat cancer."
Many research programs at Ludwig Princeton could benefit from collaborations with MacMillan's lab. These include, among other things, explorations of the effects of metabolites and fats on the function of key cancer-targeting immune cells.
MacMillan is the third prominent scientist to be appointed by the Ludwig Institute's Board of Directors as a distinguished scholar. Peter Ratcliffe, who received the 2019 Nobel Prize in Physiology or Medicine for his seminal studies of cellular oxygen sensing and hypoxia, is distinguished scholar at the Institute's Oxford Branch. Ludwig Lausanne's Distinguished Scholar Douglas Hanahan, meanwhile, is renowned for his pioneering development of mouse models of cancer and his co-authorship with Ludwig MIT Co-director Robert Weinberg of a review titled The Hallmarks of Cancer (and its updates), which remains one of the most highly cited papers in the field of cancer research.
