Associate Professor of Molecular Biology & Genetics
Publications | Research | Faculty
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.
Courses Taught:
BIOBM 439/BIOGD 439 - The Molecular Basis of Human Disease
Fall. 3 credits. Prerequisites: BIOBM 330 or BIOBM 331-332 and genetics (e.g., BIOGD 281) or permission from instructor. Recommended: cell biology (e.g., BIOBM 432 or BIOAP 316) and physiology (e.g., BIOAP 311 or BIOAP 458). S-U grades optional. Fall 2003. 3 credits. Lecs, T R 10:10 - 11:25 (75 minutes). 27 lectures. Enrollment = ~100 undergrad and grad students.
This course examines how changes in the normal expression, structure, and activity of gene products caused by genetic mutations and environmental agents lead to human diseases. The material will focus on how proteins with modified structures and biochemical activities cause alterations in normal cellular processes, as well as the physiological consequences of these changes. Topics will be selected from hormone insensitivity syndromes, inborn errors of metabolism, gene fusions resulting in hybrid proteins, gene amplification, gene inactivation, disruption of signaling pathways, disruption of metabolic pathways, and the molecular actions of environmental poisons and toxins. Examples of diseases will be selected to emphasize various aspects of cell biology, physiology, and immunology that have been presented in other courses. In addition, the methods used to identify the underlying biochemical and genetic basis of the diseases, as well as possible pharmaceutical and genetic therapies for treating the diseases, will be presented.
Links:
- Kraus Lab Web Site
- Department of Pharmacology, Weill Medical College
- Graduate Program in Biochemistry, Molecular and Cell Biology
- Graduate Program in Genetics and Development
- Graduate Program in Environmental Toxicology
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
For more on my research please visit my lab web site here.
Click here to view Dr. Kraus' PubMed listings.
Click here to view supplement materials accompanying Dr. Kraus' publications.
Ito T., Ikehara T., Nakagawa T., Kraus W. L., Muramatsu M. (2000) p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone. Genes Dev. 14:1899-1907.
Manning E. T., Ikehara T., Ito T., Kadonaga J. T., Kraus, W. L. (2001) p300 forms a stable, template-committed complex with chromatin: a role for the bromodomain. Mol. Cell. Biol. 21:3876-3887.
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 receptor coactivator 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 ER? and ER?. EMBO J. 22:600-611.
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.
Acevedo M. L. and Kraus W. L. (2004) Transcriptional activation by nuclear receptors. Essays in Biochemistry 40:73-88. (Review)
Kim M. Y., Mauro S. A., Gévry N., Lis J. T., Kraus W. L. (2004) 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).
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. Molec. Biol. 346:135-146.
Kim M. Y., Zhang, T., Kraus W. L (2005) Poly(ADP-ribosyl)ation by PARP-1: "PAR-laying" NAD+ into a nuclear signal. Genes Dev. 19:1951-1967. (Review)