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Lene Holland, PhD

Professor, Department of Medical Pharmacology and Physiology

 

Medical Pharmacology and Physiology
One Hospital Drive, M470A
Columbia, MO 65212
573-882-5373
HollandL@health.missouri.edu

 

Steroid hormones control the activity of target cells by modulating expression of specific genes. The hormones bind to receptor proteins that interact with DNA and, together with other DNA-binding proteins, stimulate or repress transcription of nearby genes. The steroid hormone receptors belong to a large family of proteins called nuclear receptors, which regulate a very wide variety of physiological processes throughout the body. The focus of research in Dr. Holland's laboratory is to analyze the molecular mechanisms underlying transcriptional regulation by the nuclear receptors. They use the liver of the frog Xenopus laevis as a model system. In the liver, synthesis of the three subunits of the critical blood-coagulation protein, fibrinogen, is controlled by adrenal steroids of the glucocorticoid class. Using several parallel approaches, including primary cell culture, introduction of purified genes into isolated liver cells, and analysis of DNA:protein binding interactions, the laboratory has identified the essential DNA sequences and protein factors required for hormone-induced expression of the fibrinogen genes. They are particularly interested in a DNA-binding protein, called Xenopus Glucocorticoid Receptor Accessory Factor (XGRAF) that is required, together with the hormone receptor, to simulate expression of the gamma fibrinogen subunit gene in response to glucocorticoids. The position of the XGRAF binding site in the gene upstream region is interesting, because it is directly adjacent to a sequence that binds a monomer of the glucocorticoid receptor (GR). They have shown that XGRAF and GR form a novel heterodimeric transcriptional regulatory complex. The long-term goal is to identify and purify XGRAF and to elucidate its unique role in glucocorticoid regulation of gene transcription. This knowledge will contribute to understanding, in general, the function of multiple protein factors acting on individual genes to elicit the appropriate overall physiological response to a steroid hormone signal.

 

More information on Dr. Holland and her lab can be found here.

Research Areas of Interest

Cancer
Cardiovascular biology/ research
Cell biology
Cellular signaling
DNA/RNA hybridization
Genetics
Genomic biology
Genomic library construction
Hormone action
Hormone assay
In vitro transcription
Molecular biology
Molecular genetics
PCR
Protein biology
Protein structure/function
Proteomics
Proteonomic analysis
Quantitative RNA/DNA analysis
Receptor biology
Signal transduction
Systems
Transfection systems