Professor, Director of Gene Expression Laboratory, The Salk Institute for Biological Studies
The activity of humans and other living organisms is governed by nerves and hormones. The receptors for insulin and other peptide hormones exist within cell membranes, and when those hormones bind with receptors, the receptors send a signal into the cell. However, fat-soluble hormones and vitamins are able to pass through the cell membrane to reach the nucleus of cells, where DNA is stored, and the receptors for such substances were once unknown. Professor Ronald Evans (PhD) was the first researcher in the world to isolate the gene-encoding glucocorticoid receptor, and successfully identify its structure and function as a nuclear receptor. He has built upon that success through a number of monumental achievements in molecular biology and endocrinology, including the cloning of numerous other nuclear receptors such as the thyroid hormone receptor (TR) and the retinoic acid receptor (RAR), which binds with retinoid active derivatives of vitamin A, and clarifying the overall picture of the nuclear receptor superfamily, which contains 48 members that regulate signal transmission.
Evans has isolated many orphan receptors (receptors for which the ligand has yet to be identified), including the estrogen-related receptors (ERR) α and β, and the retinoid X receptor (RXR), and was able to determine some of their endogenous ligands. He also discovered that RXR acts on RAR, TR, peroxisome proliferator-activated receptors (PPAR) and many other nuclear receptors to form heterodimers.
The nuclear receptor superfamily discovered by Evans, and for which he clarified the structure and functionality, is found in various tissues, and it affects various physiological functions, including metabolism, immunity, inflammation, reproduction, bone formation, cell differentiation, and cell proliferation. The superfamily is associated with numerous diseases, and therefore many drugs have been developed to target its members. For example, identifying the mechanism by which glucocorticoid receptors act has led to the development and widespread use of immunosuppressants and therapeutic drugs for various infectious diseases, rheumatoid arthritis, asthma, and more. In addition, research into vitamin A and D receptors has helped clarify the effects of fat-soluble vitamins, which has resulted in them being widely used in treating leukemia, osteoporosis, psoriasis, and other diseases. Evans not only also identified the endogenous ligand of PPARγ, a receptor closely connected to adipocyte differentiation and sugar/lipid metabolism, he was also able to determine that thiazolidine derivatives, a highly effective treatment for diabetes, also act as synthetic ligands for PPARγ. Moreover, Evans successfully cloned SMRT and other nuclear receptor coactivators that play an important role in nuclear receptor-mediated organ/tissue-specific actions, and has contributed significantly to developing clinical applications and clarifying the mechanism of action for selective estrogen receptor modulators (SERMs) typically used to treat post-menopausal osteoporosis, and anti-cancer drugs for treatment of hormone-responsive cancers (breast, uterine, prostate, etc.)
The academic contributions Evans made through clarifying the overall picture of the 48-member nuclear receptor superfamily are unparalleled, but it would also be impossible to discuss the development of drugs targeting nuclear receptors and nuclear receptor ligands without mentioning his name. His contributions to clinical medicine, pharmaceutical science, and society as a whole are remarkable.
It is for these reasons that we believe the achievements of Professor Ronald Evans make him worthy of recognition as the recipient of the 2024 Japan Prize honoring achievements in the fields of Medicine and Pharmaceutical Science.