W. Lee Kraus
Professor of Molecular Biology & Genetics

Phone

607-255-6087

Address

Department of Molecular Biology & Genetics
465 Biotechnology Building
Cornell University
Ithaca, NY 14853-2703

Email

Web Sites

Background

W. Lee Kraus is an Associate Professor in the Department of Molecular Biology and Genetics. He did his graduate research on the regulation of steroid hormone receptor activity in the laboratory of Dr. Benita S. Katzenellenbogen at the University of Illinois, Urbana-Champaign and received his Ph.D. in 1994. He did his postdoctoral research on the mechanism of transcriptional activation with chromatin templates in the laboratory of Dr. Jim Kadonaga at the University of California, San Diego. During his postdoctoral work, Dr. Kraus was supported by fellowships from the National Institutes of Health and the American Cancer Society, California Division. Dr. Kraus joined the faculty in the Department in 1999 where he has been supported by a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund, grants from the National Institutes of Health, and a grant from the American Cancer Society. Dr. Kraus holds an adjunct appointment in the Department of Pharmacology at the Weill Medical College of Cornell University in New York City (web site). He participates in the graduate fields of Biochemistry, Molecular & Cell Biology, Genetic & Development, and Environmental Toxicology at the Ithaca campus, and the graduate field of Pharmacology at the Weill campus.

Research Description

Small-Molecule Signaling and Transcriptional Regulation in the Chromatin Environment of the Nucleus
The coordinated regulation of gene expression in response to intrinsic and extrinsic cellular signals is a fundamental process in biology. My lab is interested in the basic mechanisms of nuclear signaling and gene regulation by small molecules and how these signaling pathways relate to human diseases, including cancers. We have focused our efforts on two distinct, but likely related, nuclear signaling pathways controlled by estrogens and NAD+, a metabolic cofactor whose signaling actions in the nucleus are only just beginning to be understood. My lab is combining the most powerful techniques from modern biology, as well as the physical and computational sciences, to address specific mechanistic questions that will yield an in depth understanding of the molecular basis of signal-regulated gene expression. Our interdisciplinary approach has led to new information about the connections between hormone-regulated gene expression and the gene-regulating effects of chromatin, which has implications for understanding and treating breast cancers. Furthermore, our most recent work has led to some surprising new conclusions about the activity of an NAD+-regulated nuclear factor, poly(ADP-ribose) polymerase-1 (PARP-1), connecting cellular NAD+ levels to nuclear signaling, chromatin structure, and gene expression. more

Publications

Lee K. C. and Kraus W. L. (2001) Nuclear receptors, coactivators and chromatin: new approaches, new insights. Trends Endocrin. Metab. 12:191-197. (Review)

Kim M. Y., Hsiao S. J., Kraus W. L. (2001) A role for coactivators and histone acetylation in estrogen receptor-mediated transcription initiation. EMBO J. 20:6084-6094.

Cheung E., Zarifyan A., Kraus W. L. (2002) Histone H1 represses estrogen receptor transcriptional activity by selectively inhibiting receptor-mediated transcription initiation. Mol. Cell. Biol. 22:2463-2471.

Kraus W. L. and Wong J. (2002) Nuclear receptor-dependent transcription with chromatin: is it all about enzymes? Eur. J. Biochem. 269:2275-2283. (Review)

Acevedo M. L. and Kraus W. L. (2003) Mediator and p300/CBP-steroid receptorcoactivator complexes have distinct roles, but function  synergistically, during estrogen receptor-dependent transcription with chromatin templates. Mol. Cell Biol. 23:335-348.

Cheung E., Schwabish M. A., Kraus W. L. (2003) Chromatin exposes intrinsic differences in the transcriptional activities of ERa and ERb. EMBO J. 2:600-611.

Lee K. C., Li J., Cole P. A., Wong J., Kraus W. L. (2003) Transcriptional activation by thyroid hormone receptor involves chromatin remodeling, histone acetylation, and cooperative stimulation by p300 and SRC coactivators. Molecular Endocrinology 17:908-922.

Kraus W. L. and Lis, J. T. (2003) PARP goes transcription. Cell 113:677-683. (Review)

Acevedo M. L., Lee K. C., Stender J. D., Katzenellenbogen B. S., Kraus W. L. (2004) Selective recognition of distinct classes of coactivators by a ligand-inducible activation domain. Molecular Cell 13:725-738.

Kim M. Y., Mauro S. A., Gévry N., Lis J. T., Kraus W. L. (2004) NAD+-dependent modulation of chromatin structure and transcription by nucleosome-binding properties of PARP-1. Cell 119:803-814. (Featured in a "Preview" in the same issue of Cell, p. 735 - 736).

Acevedo M. L. and Kraus W. L. (2004) Transcriptional activation by nuclear receptors. Essays in Biochemistry 40:73-88. (Review)

Cheung E., Acevedo M. L., Cole P. A., Kraus W. L. (2005) Altered  pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1. Proc. Natl. Acad. Sci. USA 102:559-564.

Brower-Toland B., Wacker D. A., Fulbright R. M, Lis J. T., Kraus W. L., Wang M. D. (2005) Specific contributions of histone tails and their acetylation to the mechanical stability of nucleosomes. J. Mol. Biol. 346:135-146

Kim M. Y., Zhang, T., Kraus W. L (2005) Poly(ADP-ribosyl)ation by PARP-1: "PARlaying" NAD+ into a nuclear signal. Genes Dev. 19:1951-1967. (Review)

Kim M. Y., Woo E., Homenko D. R., Chong Y. T. E., Kraus W. L. (2006) Acetylation of estrogen receptor alpha by p300 at lysines 266 and 268 enhances the deoxyribonucleic acid binding and transactivation activities of the receptor. Mol. Endocrinol. 20:1479-1493.
(Featured on the cover; Winner of the 2006 "Outstanding First Authored Student Paper" award for Molecular Endocrinology).

Lis J. T., Kraus W. L. (2006) Promoter cleavage: A topoIIb and PARP-1 collaboration. Cell 125:1225-1227. (Review)

Owen H. R., Elser M., Cheung E., Gersbach M., Kraus W. L., Hottiger M. O. (2007) MYBBP1a is a novel repressor of NF-κB. J. Mol. Biol. 366:725-736.

Gamble, M. J., Kraus W. L. (2007) Visualizing the histone code on LSD1. Cell 128:433-434. (Review)

Kininis M., Chen B. S., Diehl A. G., Isaacs G. D., Zhang T., Siepel A. C., Clark A. G., Kraus W. L. (2007) Genomic analyses of transcription factor binding, histone acetylation, and gene expression reveal mechanistically distinct classes of estrogen-regulated promoters. Mol. Cell. Biol. 27:5090-5104.

Wacker D. A., Ruhl D. D., Balagamwala E. H., Hope K. M., Zhang T., and Kraus W. L. (2007) The DNA binding and catalytic domains of poly(ADP-ribose) polymerase-1 cooperate in the regulation of chromatin structure and transcription. Mol. Cell. Biol. 27:7475-7485. (Featured on the cover).

Wacker D. A., Frizzell K. M., Zhang T., Kraus W. L. (2007) Regulation of chromatin structure and transcription by poly(ADP-ribose) polymerase-1: Possible targets for drug based therapies. Subcell. Biochem. 41:45-69. (Review)

Krishnakumar R., Gamble M. J., Frizzell K. M., Berrocal J. G., Kininis M., and Kraus W.L. (2008) Reciprocal binding of PARP-1 and histone H1 at promoters specifies transcriptional outcomes. Science 319:819-821.

Kininis M., Kraus W. L. (2008) A global view of transcriptional regulation by nuclear receptors: gene expression, factor localization, and DNA sequence analysis. Nucl. Recept. Signal. 6:e005. (Review)

Kraus W. L. (2008) Transcriptional control by PARP-1: chromatin modulation, enhancer binding, coregulation, and insulation. Curr. Op. Cell Biol. 20:294-302. (Review)

Click here to view Dr. Kraus' PubMed listings.