Dr. W. Lee Kraus is a molecular endocrinologist who has made significant contributions to our understanding of the mechanisms by which estrogen and nuclear NAD+ signaling pathways control gene transcription. His discoveries at the forefront of chromatin and transcriptional regulation have fundamentally changed our understanding of how signal-regulated transcription factors, coregulator complexes, and histone- and chromatin-modifying enzymes collaborate to modulate chromatin structure and gene expression in a variety of biological systems, from reproduction and metabolism to cancer and inflammation. He has developed and applied new methods and approaches, ranging from chemical, biochemical, and molecular to genomic and computational, which have led to key new observations that have changed our understanding of the importance of chromatin in transcriptional regulation. Dr. Kraus was the first to develop an in vitro chromatin assembly and transcription system that precisely and faithfully recapitulates the known physiological specificity of transcription regulation by steroid hormones acting through their cognate nuclear receptors. With this work, he moved nuclear receptor-regulated transcription into a defined molecular system where it could, for the first time, be studied using powerful biochemical analyses.
Dr. Kraus has also elucidated novel connections between nuclear NAD+ synthesis and gene regulation mediated by poly(ADP-ribose) polymerase-1 (PARP-1), an abundant and ubiquitous chromatin-associated protein. This work uncovered critical roles for PARP-1 in regulating chromatin structure and gene expression in response to extracellular signals, such as estrogens. Finally, Dr. Kraus has developed novel computational tools to integrate and analyze data from a wide variety of genomic approaches to study the immediate and direct effects of estrogen and nuclear NAD+ signaling on the transcriptome. These studies have studies have revealed the diverse ways in which genomes are organized, transcribed, and regulated. In addition, they have revealed new facets of enhancer assembly and function, as well as the expression of thousands of previously unannotated noncoding RNA transcripts of unknown function.
Dr. Kraus is a cofounder of Ribon Therapeutics, Inc.