Kraus Research Laboratory

The Kraus Lab is interested in the basic mechanisms of nuclear signaling and gene regulation by small molecules and how these signaling pathways relate to human physiology (e.g., reproduction, metabolism, cellular differentiation and development) and disease states (cancers, inflammation, stress).

We have focused our efforts on two distinct, but likely related, nuclear signaling pathways: one controlled by estrogens—a class of steroid hormones—and another controlled NAD —a metabolic cofactor whose signaling actions in the nucleus are only just beginning to be understood.

W. Lee Kraus, Ph.D., completed 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 completed his postdoctoral research on the mechanisms of transcriptional regulation with chromatin 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. Prior to joining the faculty at UT Southwestern, Dr. Kraus was a professor in the Department of Molecular Biology and Genetics at Cornell University in Ithaca, New York.  He also held a joint appointment in the Department of Pharmacology at the Weill Medical College of Cornell University in New York City.

Research Focus

The coordinated regulation of gene expression in response to intrinsic and extrinsic cellular signals is a fundamental process in biology. 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.

Research Images

Lab Overview

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NAD Signaling

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Estrogen Signaling

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Key Publications

View Dr. Kraus' complete PubMed listings.

Estrogen Signaling

  • Kraus W. L. and Kadonaga J. T. (1998) p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation.  Genes Dev. 12:331-342.
  • 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.
  • 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.
  • 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).
  • Kininis M., Isaacs G. D., Core L. J., Hah N., Kraus W. L. (2009) Post-recruitment regulation of RNA polymerase II directs rapid signaling responses at the promoters of estrogen target genes. Mol. Cell. Biol.  29:1123-1133.

Nuclear NAD Signaling and PARPs

  • 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. 
  • 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.
  • 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.
  • Zhang T., Berrocal J. G., Frizzell K. M., Gamble M. J., DuMond M. E., Krishnakumar R., Yang T., Sauve A. A., Kraus W. L. (2009) Enzymes in the NAD salvage pathway regulate SIRT1 activity at target gene promoters.  J. Biol. Chem. 284:20408-20417.
  • Frizzell K. M., Gamble M. J., Berrocal J. G., Zhang T., Krishnakumar R., Cen Y., Sauve A. A., Kraus W. L. (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.  J. Biol. Chem. 284:33926-33938.  (Faculty of 1000 recommended paper).
  • Gamble M. J., Frizzell K. M., Krishnakumar R., Kraus W. L. (2010) The histone variant macroH2A1 marks repressed autosomal chromatin, but protects target genes from silencing.  Genes Dev. 4:21-32.  (selected by Science as the editor’s molecular biology choice of the week).

Selected Reviews

  • Kraus W. L. and Lis, J. T. (2003) PARP goes transcription.  Cell  113:677-683.  (Review)
  • 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)
  • 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. (2009) New functions for an ancient domain.  Nat. Struct. Mol. Biol. 16:904-907
  • Zhang T., Kraus W. L. (2009) SIRT1-dependent regulation of chromatin and transcription: Linking NAD metabolism and signaling to the control of cellular functions.  Biochem. Biophys. Acta – Prot. Proteomics. (1804:1666-1675). (Review)
  • Ruhl D. D. and Kraus W. L. (2009) Biochemical analyses of nuclear receptor-dependent transcription with chromatin templates.  In: Chakravarti, D. (ed.) Regulatory Mechanisms in Transcriptional Signaling: Transcriptional and Physiologic Control by Nuclear Hormone Receptors.  (Series: Progress in Molecular Biology and Translational Science, vol. 87).  Elsevier.  pp. 137 - 192
  • Cheung E. and Kraus W. L. (2010) Genomic approaches to hormone signaling.  Ann. Rev. Physiol. 72:191-218.  (Review)
  • Gamble M. J., Kraus W. L. (2010) Multiple facets of the unique histone variant macroH2A: From genomics to cell biology. Cell Cycle 9: 2568 - 2574. (Review)
  • Krishnakumar R. and Kraus W. L. (2010) The PARP Side of the Nucleus: Molecular Actions, Physiological Outcomes, and Clinical Targets.  Molecular Cell (39:8-24). (Review)

Lab Members

At UT Southwestern Medical Center

Postdoctoral

Shrikanth Gadad   
sg678@cornell.edu
Research Interests: PARP-1 and chromatin structure

Christina Matulis (new)  
TBD

Graduate Students

Bryan Gibson
bag63@cornell.edu
Research Interests: PARP-1 structure-function analysis

Ziying Liu
zl254@cornell.edu
Research Interests: The role of PARPs in embryonic stem cell differentiation

Xin Luo
xl222@cornell.edu
Research Interests:  The role of PARPs in transcriptional regulation during adipogenesis  
Predoctoral Fellowship from the DOD Breast Cancer Research Program

Miao Sun
ms876@cornell.edu
Research Interests: Protein kinases in estrogen-dependent transcriptional regulation
Predoctoral Fellowship from the American Heart Association

Research Support

Jane Bowman
jane.bowman@utsouthwestern.edu

Deborah Miller  
Lab Manager
deborah.miller@utsouthwestern.edu

Fang Ye
fy44@cornell.edu
Research Interests: Role of PARPs in inflammatory responses in myometrial and cervical cells

At Cornell University

Postdoctoral

Charles Danko
dankoc@gmail.com
Research Interests: Evolutionary changes in the location of cis-regulatory elements
Postdoctoral Fellowship from the PhRMA Foundation

Graduate Students

Kristine Frizzell
kmf36@cornell.edu
Research Interests: Role of PARP-1 and PARG in the regulation of gene expression
Predoctoral Fellowship from the American Heart Association

Nasun Hah  
nh57@cornell.edu
Research Interests:Mechanisms and global analyses of estrogen-dependent transcription