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Department of Pharmacology

Department of Pharmacology
 

Mair Churchill, PhD

Professor


Contact Information:

University of Colorado Denver
Department of Pharmacology
Mail Stop 8303, RC1-South
12801 East 17th Ave
Aurora CO 80045

Phone: (303) 724-3670
Fax: (303) 724-3663
E-mail: mair.churchill@ucdenver.edu
curriculum vitae
View Our Crystal Structures

Affiliated Programs

 

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Research Interests

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 from cancer and heart disease to bacterial infections and will assist in drug development efforts.

Our studies focus on the following questions:

  1. How is chromatin structure modulated for DNA-dependent processes?
  2. How do transcription factors and pioneering factors activate gene expression?
  3. How are genes coordinately regulated by quorum sensing in bacterial pathogens?

Current projects

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. nucleosome dynamicsThis 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. HMGB proteinsThe 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.

Progesterone receptor-coregulator interactions.
progesterone receptorRegulation of gene expression through changes in chromatin structure is important in human hormone dependent malignancies mediated by steroid receptor transcription factors. The steroid hormone receptors, in particular, are affected by HMGB proteins and Jun dimerization protein 2 (JDP-2) binding through currently unknown mechanisms. We are determining the mechanisms by which these proteins coactivate gene expression of the progesterone receptor. Since these factors regulate the activity of the steroid hormone receptors, blocking these interactions may prove to be an effective way to decrease hormone activity in certain cancers.

Quorum sensing

quorum sensingAs we have entered the post-antibiotic era, it is more important now than ever before to understand the molecular and structural basis of bacterial pathogenicity. Opportunistic bacteria infect immune-compromised, cystic fibrosis and cancer chemotherapy patients, and cause serious complications in their treatment. A mechanism called quorum sensing regulates bacterial virulence by altering gene expression on a global scale. Quorum sensing is the ability of the bacteria to sense their local concentration, and in gram negative bacteria depends on a simple lipid mediator called acyl-homoserinelactone (AHL) that is synthesized by an AHL-synthase (LasI for example). The AHL is detected by a transcription factor, in this case LasR. We are studying the quorum sensing systems in several Gram negative species to understand the mechanistic basis for AHL synthesis and specificity as well as AHL detection. These studies provide the foundation for the development of pharmacological agents for treatment of persistent as well as multi-drug resistant forms of bacterial infection.

Churchill Lab 2013

Current Lab Members

 Results From Personnel : Selected site and subsites
First NameLast NameMiddle InitialDegreePosition
VishantieDostalK.BSGraduate Student
WallaceLiuH.BSGraduate Student
ChristopherMalarkeyS.PhDPostdoctoral Fellow
MichelleWilliams BSProfessional Research Assistant
ChristinaWysoczynskiL.BSGraduate Student

Previous Trainees

 Results From Personnel : Selected site and subsites
First NameLast NameMiddle InitialDegreePosition
PamelaDavid GerechtS.PhDResearch Associate
KimberlyDeckerJ.PhDPostdoctoral Fellow
DouglasDonhamC.BSGraduate Student
LeahFeeleyR.BSGraduate Student
ToddGanglehoff BSGraduate Student
TyGouldA.W.PhDGraduate Student
JacobHerman PhDPostdoctoral Fellow
KristaHillK.BSGraduate Student
SamuelMungalachettyP.PhDPostdoctoral Fellow
SarahRoemerC.PhDPostdoctoral Fellow
LukeSmith BSSenior Professional Research Assistant
PrinceTiekuM.MSGraduate Student
WilliamWatsonT.PhDGraduate Student
DonaldZapien PhDPostdoctoral Fellow

 



​Chris Malarkey

Postdoctoral Fellow, Department of Pharmacology
Ph.D. Loyola University of Chicago (Biochemistry)
B.S. Loyola University Chicago (Chemistry)
 
Research: Mitochondrial transcription
 


​Christina Wysoczynski

Ph.D. Student, Department of Pharmacology
B.S., University of West Georgia, Carrollton (Biology)
 
Research: Mechanism of Acyl-homoserine lactone synthesis in quorum sensing


​Wallace Liu

Ph.D. Student, Department of Pharmacology
B.S., University of California, San Diego (Biochemistry and Cell Biology)
 
Research: Chromatin assembly
 


Vishantie Dostal

Ph.D. Student, Structural Biology and Biochemistry
B.S., University of Rhode Island (Biological Science)
 
Research: Mitochondrial transcription

 

​Postdoctoral positions available

A Postdoctoral Associate position in structural and molecular biology in the Department of Pharmacology, University of Colorado School of Medicine, Full Time 100%

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 laboratory studies structural and mechanistic aspects of gene regulatory systems in eukaryotes and bacterial pathogenesis using biochemical, biophysical, and x-ray crystallographic methods.
 
Candidates are expected to have a Ph.D. in Structural Biology, Biochemistry, Chemistry, Pharmacology, or have investigated a closely related field for their Ph.D. research project. Experience with basic biochemical or computational methodology is required.  Evidence of a strong commitment to research from strong publications and letters of reference is required.
 
Interested applicants are invited to send a Curriculum vitae and the names and contact information to Mair Churchill, Ph.D., MS 8303, PO Box 6511, Aurora, CO 80045, or email.
 
The University of Colorado offers a full benefits package.  Information on University benefits programs, including eligibility, is located at the payroll and benefits site.
 
The University of Colorado is committed to diversity and equality in education and employment
 

Predoctoral Research Programs

The lab is available for predoctoral research to UCD Ph.D. students in the Pharmacology, BSP, Biochemistry, Molecular Biology, Microbial pathogenesis, and MSTP training programs. Students from other University of Colorado campuses and programs may also be eligible. Please contact Dr. Mair Churchill directly for more information if interested.
 

Summer Research Opportunities

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.

​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