David C. Klein, Ph.D., has made seminal contributions to the fields of chronobiology and neuroendocrinology through work on the pineal gland.
Dr. Klein received his B.A. from Cornell University and his Ph.D. from Rice University, where he studied the role of calcitonin in bone metabolism under Roy Talmage. During postdoctoral work at the University of Rochester with Larry Raisz, he discovered that prostaglandins promote bone resorption, which has had broad clinical impact. While at Rochester, he initiated independent work on the pineal gland. This research continued after joining NICHD in 1969 and grew into one of the leading research programs devoted to the pineal gland.
During his career, Dr. Klein established productive collaborations with experts in a broad range of disciplines including functional neuoanatomy, molecular biology, pharmacology, electrophysiology, histology, and structural biology. The advances resulting from these collaborations enriched and invigorated the field of pineal research. Specific advances include contributions to understanding the role of the suprachiasmatic nucleus as “The Mind’s Clock” in controlling circadian rhythms; a detailed description of the mechanisms involved in regulating melatonin production focused on arylalkylamine N-acetyltransferase; the role of 14-3-3 proteins as functional regulators, studies on daily changes in the pineal transcriptome; and a theory explaining the evolution of the pineal gland and retina from a common photodetector.
Dr. Klein was appointed Scientist Emeritus in 2015 and continues to participate in research through an international network of scientists. He is currently investigating melatonin-related signaling; pinealocyte heterogeneity using single-cell RNA sequencing; circadian system organization; neural regulation of RNA isoforms; and 24-hour dynamics in the transcriptomes of the pineal gland, retina, suprachiasmatic nucleus and other tissues. Dr. Klein has contributed over 400 publications to the biomedical literature.
The Section on Neuroendocrinology has a broad interest in the role that the pineal gland plays in biology, with special interest in melatonin and how the production of melatonin is regulated by the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (AANAT, EC220.127.116.11).
Current areas of research include:
- Functional analysis of the AANAT/14-3-3 regulatory complex
- Identification of new AANAT binding partners using yeast two hybrid system and affinity approaches
- Characterization of cAMP and clock dependent transcriptional mechanisms controlling AANAT gene expression
- Analysis of mechanisms involved in regulating proteasomal proteolysis of AANAT
Recent advances include:
- Discovery that a cyclic AMP operated switch controls binding of AANAT to 14-3-3 proteins
- Determination of the 3-D crystal structure of the AANAT/14-3-3 regulatory complex
- Demonstration that 14-3-3 binding activates and shields AANAT
- Use of the AANAT promoter for pineal/retina specific gene targeting
- Development of cell lines expressing AANAT
- Discovery that minute-to-minute neural control of AANAT protein in vertebrates involves blocking rapid proteasomal proteolysis