Current Research
The emphasis of our research is on theoretical and medical problems related to the role of transcription factors (STAT5) that mediate cytokine action and histone methyltransferases (EZH1 and EZH2). Using traditional and cell-specific gene knock-out mice, researchers in LGP have discovered that STAT5 is essential for the development and function of several distinct cell types, including the mammary gland and liver.
Current research is aimed towards an understanding the genetic and epigenetic logic that controls cell specific functions of the transcription factor STAT5 and histone methyltransferases in mammary tissue and liver.
LGP scientists have discovered that cytokine-STAT5 signaling is essential for the establishment of mammary alveolar progenitor cells (Yamaji et al., 2009). Using large scale genomic and genome-wide transcription factor binding and gene expression profiling LGP scientists continue to explore the chromatin landscape of mammary stem and cells throughout mammary development (Yamaji et al., 2012). These studies will provide insight into mechanisms used by STAT5 to control lineage decision-making, cell proliferation and differentiation. These studies have also identified micro RNAs that are controlled during mammary development by STAT5. Mouse genetics and primary cell culture systems are being employed to further uncover physiological roles of these microRNAs
For more information contact Lothar Hennighausen.
Scientific Milestones:
1982 Isolation of mammary specific mRNAs
1984 Cloning of milk protein genes
1987 Discovery and characterization of transcription complexes on the HCMV-IE1 enhancer
1987 Development of the mammary gland bioreactor: first mouse to express a human pharmaceutical protein in its milk
1988 Discovery that hormonal regulation of milk protein gene expression is mediated by promoter elements
1992 First transgenic pig to express a foreign protein in its milk
1994 Establishment of the tetracycline regulated gene expression system in transgenic mice
1996 Verification of the multi hit theory during tumor progression
1997 Discovery that mammary development and function depends on the Stat5a transcription factor
1997 Targeting the Cre-lox recombination system to the mammary gland
1998 Discovering a role of C/EBPbeta signaling in the mammary development
1999 Deletion of the Brca1 gene from mammary epithelium using Cre-loxP recombination
2000 Bcl-x is required for the survival of fetal germ cells and mature erythrocytes, but not immature ones
2001 Bcl-x is required for controlled remodeling of mammary tissue
2001 Stat5 is required for the proliferation and differentiation of mammary epithelial cells (Miyoshi)
2002 Jak2 is required for pregnancy-mediated development of mammary epithelial cells
2002 Beta-catenin expression determines mammary epithelial cell identity
2002 Id2 is required for development of mammary epithelial cells at pregnancy
2002 Signaling via the IL6/gp130 pathway is important for mammary gland involution
2003 The characterization of protein markers for the analysis of mammary epithelial cell development
2004 Complete and cell-specific inactivation of the mouse Stat5 locus (Cui)
2006 Redefining the role of Stat5 in lymphoid development (Yao)
2006 Notch-RBPJ signaling defines cell lineages in mammary development (Buono)
2007 STAT5 controls muscle giber composition (Klover)
2010 STAT1 modulates mammary cancer (Klover)
2010 Cytokines modulate liver cancer through STAT5 and cell cycle proteins (Yu)
2012 Dissecting mechanisms underlying the progressive development of mammary tissue during pregnancy (Yamaji)
2013 Meta analysis of a transcription factor family (Kang)
Current Collaborators:
- John O’Shea (NIAMS)
- Warren Leonard (NHLBI)
- Simon Choi (Gwangju)
- Jee-Yeon Yoo (Pohang)
- Kyudong Han (Cheonan)
- Bernd Groner (Frankfurt)
- Bing Mei Zhu (Nanjing)