University of Colorado Denver
Department of Pharmacology
Mail Stop 8303, RC1-South
12801 East 17th Ave
Aurora CO 80045
My lab is interested in understanding the molecular basis of essential processes that regulate gene expression. We use biophysical, biochemical methods, and structural methods, including X-ray crystallography. Our insights into these fundamental mechanisms will contribute to a better understanding and ability to regulate gene expression processes involved in human diseases and will assist in drug development efforts.
Our studies focus on the following questions:
Modulation of chromatin structure
The eukaryotic genome is packaged by histones into nucleosomes that together with non-histone proteins form higher order structures known as chromatin. This chromatin structure must be dismantled for factors that carry out the processes of transcription, replication, DNA repair, and recombination to gain access to the DNA. Numerous protein-DNA interactions, protein-protein interactions, and covalent modifications actively regulate DNA accessibility, but the molecular mechanisms by which this dynamic remodeling of chromatin occurs are still not well understood. Therefore, we will need to understand chromatin assembly, disassembly, nucleosome remodeling and accessibility, and gene regulatory processes at the molecular level in order to achieve the ultimate goal of being able to modulate the activity of genes at will.
Nucleosome dynamics play an important role in activated gene expression. We are studying the histone chaperone Asf1, because of its central role in chromatin dynamics. Asf1 binds to a dimer of histones H3 and H4, carrying the histones for post-translational modifications and hand-off to other histone chaperones in the cell. Chromatin assembly and disassembly systems are essential and fundamental to all DNA-dependent cellular functions, and are also important in human cancer and aging processes.
HMGB proteins. The structure of chromatin is also modulated by abundant proteins that bind DNA non-sequence-specifically. The high mobility group (HMGB) proteins are among the most abundant of these ‘non-sequence-specific proteins’ with the exception of histones in the typical human cell. We study the HMGB proteins to understand how they recognize DNA, form higher order structures in chromatin, and facilitate transcriptional activation of target genes. HMGB proteins bend DNA dramatically and participate in nucleosome positioning and mobility.
|First Name||Last Name||Middle Initial||Degree||Position|
|First Name||Last Name||Middle Initial||Degree||Position|
|Pamela||David Gerecht||S.||PhD||Research Associate|
|Luke||Smith||BS||Senior Professional Research Assistant|
NIH-funded postdoctoral position available in the areas of structural biology in the Department of Pharmacology at the University of Colorado School of Medicine in Denver, Colorado.
The lab is available for a summer research opportunuty for students majoring in Biology, Biochemistry, Chemistry, or a related field. Please contact Dr. Mair Churchill directly if interested before the middle of April each year.
Congratulations Vishantie and Mair on the most recent publication in Biochimica et Biophysica Acta-Gene Regulatory Mechanisms entitled, “Cytosine methylation of mitochondrial DNA at CpG sequences impacts transcription factor A DNA binding and transcription“. 2/2019
Congratulations Ying-Chih Chi (aka Thomas). Thomas is leaving us to begin another phase in his career at Columbia in the cyro-EM facility. 1/2019
Congratulations Vishantie Dostal. Vishantie successfully defended her Ph.D. and will be leaving us to begin her post-doctoral studies. 11/2018
Congratulations Mair on the most recent publication in Mol Microbiol entitled, “Mechanism of agonism and antagonism of the Pseudomonas aeruginosa quorum sensing regulator QscR with non-native ligands”. 2/2018
We would like to welcome our newest graduate student Ruben to our lab. 7/2017
Welcome Ying-Chih Chi (aka Thomas). Thomas will be joining us as a postdoc in October. He received his PhD from UCDenver Anschutz in Changwei Liu Lab and also spent some time in Elan Eisenmeser Lab. Welcome Thomas! 10/2016
Best of luck Wallace Liu. Wallace is off to the University of Wisconsin-Madison to begin his postdoc studies. 10/2016
Congradulations Wallace Liu and Yeyun Zhou on the most recent publication in eLife entitled, "The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones”. 9/2016
Welcome Ruben Rosas-Ospina. Ruben is a Structural Biology rotation student for the fall of 2016. 8/2016
Welcome Joshua Abbott. Josh is a Structural Biology rotation student for the winter of 2015-2016. 11/2015 - 2/2016
Welcome Brett Dunn. Brett is a Pharmacology rotation student for the fall of 2015-2016. 8/2015 - 11/2015
Welcome Christal Davis. Christal is a Structural Biology rotation student for the fall of 2015-2016. 8/2015 - 11/2015
Congratulations to Chris Malarkey on his paper publication in Acta Crystallogr D Biol Crystallogr. 7/2015
Welcome Kenneth Felsenstein. Kenny is our first MSTP rotation student for the summer of 2015. 6/2015 - 8/2015
Welcome Yeyun Zhou. Yeyun will begin her postdoc in our lab in October. She received her PhD from Cornell University in the lab of Richard Cerione. 10/2014
Congratulations to Chrissy Wysoczynski on her paper publication in Cell Signal. 9/2014
Congratulations to Chris Malarkey on his paper publication in PNAS. 3/2014
Welcome Shravida Shetty. Shravida is our first Molecular Biology rotation student for fall of 2014. 8/2014 - 11/2014
Congratulations to Chris Malarkey. He will soon be leaving us to begin his new job as a faculty member at Regis University. 6/2014
Congratulations to Chrissy and Chris for our most recent publications in NAR and PNAS. 11/2014, 3/2014
We would like to welcome our newest graduate student Vishantie to our lab. 6/2013