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Kraus, William Lee
Cornell Faculty Member
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Positions
- Adjunct Professor, Molecular Biology and Genetics (MBG), College of Agriculture and Life Sciences (CALS) - 2011
- Professor, Molecular Biology and Genetics (MBG), College of Agriculture and Life Sciences (CALS) - 2011
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 a joint appointment in the Department of Pharmacology at the Weill Medical College of Cornell University in New York City. 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. Dr. Kraus` primary teaching interests and responsibilities are in the molecular basis of human disease.
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Affiliations
Research
research overview
- My laboratory is interested in understanding how small-molecule signals alter the activity of factors that modulate chromatin structure to control gene expression. Although we study fundamental mechanisms, we are interested in the role that these processes play in human diseases, especially cancers, but also inflammatory, neurological, and cardiovascular diseases. We have focused our efforts on two distinct, but likely interrelated, nuclear signaling pathways: one controlled by estrogens, a class of steroid signaling molecules, and another controlled by nicotinamide adenine dinucleotide (NAD+) and its metabolites, a group of compounds whose signaling actions in the nucleus are just beginning to be understood. My lab is combining a variety of 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 in the chromatin environment of the nucleus. Our interdisciplinary approach has led to new information about the connections between nuclear signaling and the gene-regulating effects of chromatin, opened up unexplored avenues of investigation, and challenged existing models of NAD+ and estrogen signaling.
research activities
area(s) of concentration/expertise
keywords
- NAD+
- cancer
- chromatin
- disease
- endocrinology
- estrogen
- poly(ADP-ribose) polymerase (PARP)
- signaling
- transcription
submitted impact statement
- The molecular actions of estrogens provide clues for developing more effective drugs for the treatment of breast cancers.
- Research on the molecular actions of estrogens provides clues for developing more effective drugs for the treatment of breast cancers
- New molecular targets for treating diseases related to cellular stress
Publications
individual publications
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academic article
- Estrogen regulates JNK1 genomic localization to control gene expression and cell growth in breast cancer cells. Molecular Endocrinology. 2012
- Activation of estrogen receptor α by raloxifene through an activating protein-1-dependent tethering mechanism in human cervical epithelial cancer cells: A role for c-Jun N-terminal kinase. Molecular and Cellular Endocrinology. 348:331-338. 2012
- A rapid,extensive, and transient transcriptional response to estrogen signaling in breast cancer cells. Cell. 145:622-634. 2011
- Evolution of ligand specificity in vertebrate corticosteroid receptors. BMC Evolutionary Biology. 11. 2011
- Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.. Journal of Biological Chemistry. 284:20408-20417. 2009
- Global regulation of gene expression by poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) in MCF-7 human breast cancer cells. Journal of Biological Chemistry. 284:33926-33938. 2009
- New functions for an ancient domain. Nature Structural and Molecular Biology. 16:904-907. 2009
- PARP inhibitors and the treatment of breast cancer: beyond BRCA1/2? . Breast Cancer Research. 11:111. 2009
- Post-recruitment regulation of RNA polymerase II directs rapid signaling responses at the promoters of estrogen target genes. Molecular and Cellular Biology. 29:1123-1133. 2009
- A global view of transcriptional regulation by nuclear receptors: gene expression, factor localization, and DNA sequence analysis. Nuclear Receptor Signaling. 6. 2008
- Development of a Stable Dual Cell-Line GFP Expression System to Study Estrogenic Endocrine Disruptors. Biotechnol. Bioeng.. 101:1276-1287. 2008
- Development of a stable dual cell-line GFP expression system to study estrogenic endocrine disruptors. Biotechnology and Bioengineering. 101:1276-1287. 2008
- Reciprocal binding of PARP-1 and histone H1 at promoters specifies transcriptional outcomes. Science. 319:819-821. 2008
- Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation. Current Opinion in Cell Biology. 20:294-302. 2008
- Estrogen regulated gene networks in human breast cancer cells: involvement of E2F1 in the regulation of cell proliferation. Molecular Endocrinology. 21:2112-2123. 2007
- Genomic analyses of transcription factor binding, histone acetylation, and gene expression reveal mechanistically distinct classes of estrogen-regulated promoters. Molecular Biology of the Cell. 27:90-104. 2007
- Genomic analyses of transcription factor binding, histone acetylation, and gene expression reveal mechanistically distinct classes of estrogen-regulated promoters. Molecular and Cellular Biology. 27:5090-5104. 2007
- MYBBP1a is a novel repressor of NF-B. Journal of Molecular Biology. 366:725-736. 2007
- Poly(ADP-ribose) polymerase 1 is inhibited by a histone H2A variant, macroH2A, and contributes to silencing of the inactive X chromosome. Journal of Biological Chemistry. 282:12851-12859. 2007
- Regulation of chromatin structure and transcription by poly(ADP-ribose) polymerase-1: Possible targets for drug based therapies. Sub-Cellular Biochemistry. 41:45-69. 2007
- The DNA binding and catalytic domains of poly(ADP-ribose) polymerase-1 cooperate in the regulation of chromatin structure and transcription. Molecular and Cellular Biology. 27:7475-7485. 2007
- Visualizing the histone code on LSD1. Cell. 128:433-434. 2007
- Acetylation of estrogen receptor alpha by p300 at lysines 266 and 268 enhances the deoxyribonucleic acid binding and transactivation activities of the receptor. Molecular Endocrinology. 20:1479-1493. 2006
- Promoter cleavage: a topoII-beta and PARP-1 collaboration. Cell. 125:1225-7. 2006
- Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription. EMBO Journal. 25:4490-4502. 2006
- Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1. Proceedings at the National Academy of Science USA. 102:559-564. 2005
- Interactions between subunits of Drosophila Mediator and activator proteins. Trends in Biochemical Sciences. 30:245-9. 2005
- Poly(ADP-ribosyl)ation by PARP-1: "PAR-laying" NAD+ into a nuclear signal. Genes & Development. 19:1951-1967. 2005
- Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination. Proceedings at the National Academy of Science USA. 102:3611-3616. 2005
- Specific Contributions of Histone Tails and their Acetylation to the Mechanical Stability of Nucleosomes. Journal of Molecular Biology. 346:135-146. 2005
- Isoflavone stimulates core histone acetylation mediated by estrogen receptor alpha. Biochemical and Biophysical Research Communications. 317:259-264. 2004
- NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell. 119:803-14. 2004
- Selective recognition of distinct classes of coactivators by a ligand-inducible activation domain. Molecular Cell. 13:725-738. 2004
- The role of the C-terminal extension (CTE) of the estrogen receptor and DNA binding domain in DNA binding and interaction with HMGB. Journal of Biological Chemistry. 279:14763-14771. 2004
- A novel Arabidopsis acetyltransferase interacts with the geminivirus movement protein NSP. Plant Cell. 15:1605-1618. 2003
- Chromatin exposes intrinsic differences in the transcriptional activities of ER and ER. EMBO Journal. 22:600-611. 2003
- Mediator and p300/CBP-steroid receptor coactivator complexes have distinct roles, but function synergistically, during estrogen receptor -dependent transcription with chromatin templates. Molecular and Cellular Biology. 23:335-348. 2003
- PARP Goes Transcription (Review). Cell. 113:677-683. 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. 2003
- Histone H1 represses estrogen receptor transcriptional activity by selectively inhibiting receptor-mediated transcription initiation. Molecular and Cellular Biology. 22:2463-2471. 2002
- Nuclear receptor-dependent transcription with chromatin: is it all about enzymes?. Eur. J. Biochem.. 269:2275-2283. 2002
- p300-mediated Tax transactivation from recombinant chromatin: histone tail deletion mimics coactivator function. Molecular and Cellular Biology. 22:127-137. 2002
- A role for coactivators and histone acetylation in estrogen receptor α-mediated transcription initiation. EMBO Journal. 20:6084-6094. 2001
- Nuclear receptors, coactivators and chromatin: new approaches, new insights. Trends Endocrin. Metab.. 12:191-197. 2001
- p300 forms a stable, template-committed complex with chromatin: a role for the bromodomain. Molecular and Cellular Biology. 21:3876-3887. 2001
- The phosphorylation status of a signal-dependent activator is modulated via a chromatin-dependent mechanism. Molecular and Cellular Biology. 20:1596-1603. 2000
- p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone. Genes Dev.. 14:1899-1907. 2000
- Biochemical analysis of distinct activation functions in p300 that enhance transcription initiation with chromatin templates. Molecular and Cellular Biology. 19:8123-8135. 1999
- Estrogen receptor regulation of the Na+/H+ exchanger regulatory factor. Endocrinology. 140:2976-2982. 1999
- Hormone induction of progesterone receptor (PR) messenger ribonucleic acid and activation of PR promoter regions in ovarian granulosa cells: evidence for a role of cyclic adenosine 3', 5'-monophospate but not estradiol. Molecular Endocrinology. 12:1201-1214. 1998
- p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation. Genes Dev.. 12:331-342. 1998
- Determinants for the repression of estrogen receptor transcriptional activity by ligand-occupied progestin receptors. J. Steroid Biochem. Molec. Biol.. 63:175-188. 1997
- Identification of a novel transferable cis element in the promoter of an estrogen-responsive gene that modulates sensitivity to hormone and antihormone. Molecular Endocrinology. 11:330-341. 1997
- Antiestrogens: mechanisms and actions in target cells. The Journal of Steroid Biochemistry and Molecular Biology. 53:387-393. 1995
- Inhibitory cross-talk between steroid hormone receptors: differential targeting of estrogen receptor in the repression of its transcriptional activity by agonist- and antagonist-occupied progestin receptors. Molecular and Cellular Biology. 15:1847-1857. 1995
- Ligand-dependent, transcriptionally productive association of the amino- and carboxyl-terminal regions of a steroid hormone nuclear receptor. Proceedings at the National Academy of Science USA. 92:12314-12318. 1995
- Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase and cAMP-regulated gene transcription. Proceedings at the National Academy of Science USA. 91:8517-8521. 1994
- Identification of multiple, widely spaced estrogen-responsive regions in the rat progesterone receptor gene. Molecular Endocrinology. 8:952-969. 1994
- Cloning of the rat progesterone receptor gene 5'-region and identification of two functionally distinct promoters. Molecular Endocrinology. 7:1603-1616. 1993
- Regulation of progesterone receptor gene expression in the rat uterus: modulation of estrogen actions by progesterone and sex steroid hormone antagonists. Endocrinology. 132:2371-2379. 1993
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booksection
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chapter
- Biochemical analyses of nuclear receptor-dependent transcription with chromatin templates. Regulatory Mechanisms in Transcriptional Signaling: Transcriptional and Physiologic Control by Nuclear Hormone Receptors. 137-192. 2009
- Regulation of chromatin structure and transcription by poly(ADP-ribose) polymerase-1: Possible targets for drug based therapies. Chromatin and Disease. Subcellular Biochemistry Series. 45-69. 2007
- Transcriptional activation by nuclear receptors. Essays in Biochemistry. 73-88. 2004
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conference paper
- Estrogen-receptor and antiestrogen-receptor complexes: cell- and promoter-specific effects and interactions with second messenger signaling pathways. Organ Selective Actions of Steroid Hormones. Ernst Schering Research Foundation Workshop 16. 1995
featured in archived article
Teaching
teaching overview
- My major goals for teaching at both the undergraduate and graduate levels are the following: (1) To develop and teach courses in modern biology that bring together ideas and concepts from a diverse array of subject areas. In my position at Cornell University, I have done this in an effort to provide breadth and integration to a curriculum largely comprised of highly focused, in-depth, and somewhat disconnected courses. I am particularly interested in highlighting cutting-edge research and knowledge at the forefront of research in the post-genomic era. (2) To develop and teach courses that will be of practical use to the students as they progress through their careers. (3) To be accessible to my students, creating an atmosphere that encourages them to express their ideas and to seek help when they need it. (4) To explore and develop new ways to increase student involvement and participation in the classes that I teach. This has been a challenge in the large (~80 students) lecture course that I teach at Cornell University, but I have developed some effective approaches. (5) To use current electronic and web-based methods for the presentation and dissemination of information to my students (including PowerPoint lecture presentations, real-time web-based exercises in class, course e-mail, a web-page with down-loadable lecture handouts and journal articles). (6) To continue to blend my research and teaching interests in the molecular basis of human disease.
Service
service to the profession
- America Society for Microbiology Member 2000 -
- The Endocrine Society Committee Member 1996 -
- American Association for the Advancement of Science Member 1994 -
- Annual Meeting Steering Committee of the Endocrine Society Conference-Related 2006 - 2009
- AI-SPER-0203DF692AB00010802 Program Organizer 2007 - 2008
Background
education and training
- Ph.D. in, University of Illinois, Urbana-Champaign 1994
- M.S. in, University of Illinois, Urbana-Champaign 1991
- B.S. in, Cornell University 1989
awards and honors
- Excellence in Mentoring Undergraduate Students in Independent Research Award, 2008
- Richard E. Weitzman Memorial Award, given to "an exceptionally promising young investigator", 2007
- Distinguished Alumni Award, 2006
- Young Faculty Teaching Excellence Award, 2004
- International Travel Grant, 2001
- Travel Award, Special Conference on the Steroid Receptor Superfamily, 1999
- Travel Award, 81st Annual Meeting, 1999
- California Division Postdoctoral Fellowship, 1998
- Career Award in the Biomedical Sciences (1998-2002), 1998
- NIH Postdoctoral Fellowship in Molecular Biology (1995-1998), 1995
- NIH Graduate Fellowship in Cell and Molecular Biology (1989-1992), 1989
Other
alternate name
- W. Lee Kraus
college
- CALS
research keyword
- NAD+
- cancer
- chromatin
- disease
- endocrinology
- estrogen
- poly(ADP-ribose) polymerase (PARP)
- signaling
- transcription
name prefix
- Dr.