Areas of Interest
The Kerppola laboratory uses original experimental approaches to investigate molecular processes in living cells and to develop new therapies for cancers and cardiovascular diseases. Current areas of investigation in the laboratory include:
1. Molecular interactions in living cells and animals. We study interactions among proteins and other macromolecules in their normal cellular environments by visualizing the complexes they form in vivo. We have developed imaging tools, including bimolecular fluorescence complementation (BiFC) analysis, that enable us to detect interactions among different macromolecules under native conditions. (Deng, 2014) (Hu, 2002)
2. Nucleoprotein complex binding specificity and dynamics. We investigate the roles of transcription factor complexes in the control of gene expression. We use a wide range of experimental approaches ranging from fluorescence assays in vitro, in cells and in animals to studies of genome-wide chromatin occupancy. (Deng, 2014) (Burns, 2012)
3. Protein modifications in living cells. We investigate how post-translational modifications alter the functions of proteins in their normal environments by visualizing the modified conjugates in vivo. We have developed imaging tools, including ubiquitin-mediated fluorescence complementation (UbFC) analysis, that enable us to selectively detect specific modified proteins in cells. (Vincenz, 2008) (Fang, 2004)
4. Chromatin and epigenetic regulation. We investigate how chromatin binding proteins bind to specific genomic regions and how their occupancy is maintained over multiple cell generations. We have developed complementation approaches to visualize and purify specific chromatin-associated complexes by the isolation of BiFC-stabilized complexes (iBiSC). (Deng, 2014) (Cheng, 2014) (Ren, 2011) (Vincenz, 2008)
5. Transcription regulatory mechanisms. We investigate how DNA and chromatin-binding proteins act in concert to regulate transcription. We use high-throughput sequencing approaches to characterize the binding and regulatory specificities of combinations of interaction partners (Cheng, 2014) (Deng, 2013) (Burns, 2012) (Ren, 2011)
6. Diseases and development. Many of the studies in our laboratory focus on disease mechanisms and developmental programs. These studies seek to develop new therapeutic approaches and to identify new relationships between development and responses to drugs and environmental chemicals. (Burns, 2017) (Cheng, 2016) (Deng, 2013)
Published Articles or Reviews
Selected Publications
Keap1 moderates the transcription of virus induced genes through G9a-GLP and NFκB p50 recruitment.
Burns VE, Kerppola TK.
Immunology. 2022; 167: 105–21.
Virus Infection Induces Keap1 Binding to Cytokine Genes, Which Recruits NF-κB p50 and G9a-GLP and Represses Cytokine Transcription.
Burns VE, Kerppola TK.
J Immunol. 2021; 207: 1437–47.
ATR-101 inhibits cholesterol efflux and cortisol secretion by ATP-binding cassette transporters, causing cytotoxic cholesterol accumulation in adrenocortical carcinoma cells.
Burns VE, Kerppola TK.
Br J Pharmacol. 2017; 174: 3315–32.
ATR-101 disrupts mitochondrial functions in adrenocortical carcinoma cells and in vivo.
Cheng Y, Kerppola RE, Kerppola TK.
Endocr Relat Cancer. 2016; 23: 1–19.
Visualization of the Drosophila dKeap1-CncC interaction on chromatin illumines cooperative, xenobiotic-specific gene activation.
Deng H, Kerppola TK.
Development. 2014; 141: 3277–88.
KAP1 represses differentiation-inducible genes in embryonic stem cells through cooperative binding with PRC1 and derepresses pluripotency-associated genes.
Cheng B, Ren X, Kerppola TK.
Mol Cell Biol. 2014; 34: 2075–91.
Regulation of Drosophila metamorphosis by xenobiotic response regulators.
Deng H, Kerppola TK.
PLoS Genet. 2013; 9: e1003263.
Opposite orientations of a transcription factor heterodimer bind DNA cooperatively with interaction partners but have different effects on interferon-β gene transcription.
Burns V, Kerppola TK.
J Biol Chem. 2012; 287: 31833–44.
REST interacts with Cbx proteins and regulates polycomb repressive complex 1 occupancy at RE1 elements.
Ren X, Kerppola TK.
Mol Cell Biol. 2011; 31: 2100–10.
Different polycomb group CBX family proteins associate with distinct regions of chromatin using nonhomologous protein sequences.
Vincenz C, Kerppola TK.
Proc Natl Acad Sci USA. 2008; 105: 16572–7
Ubiquitin-mediated fluorescence complementation reveals that Jun ubiquitinated by Itch/AIP4 is localized to lysosomes.
Fang D, Kerppola TK.
Proc Natl Acad Sci USA. 2004; 101: 14782–7.
Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation.
Hu CD, Chinenov Y, Kerppola TK.
Mol Cell. 2002; 9: 789–98.
For a list of publications from PubMed, click HERE
