Biochemistry and Molecular Biology

University of Texas Medical Branch


Faculty

Cheryl S. Watson, Ph.D., Professor

Education:

  • BS and MS, Purdue University, 1972 and 1974
  • PhD in Cell Biology, Baylor College of Medicine, 1980
  • Postdoc at Nat’l Inst. Medical Research, London (Estrogen Action)
  • Postdoc at Population Council at Rockefeller Univ (Androgen Action)
  • ELAM (Executive Leadership in Academic Medicine) Fellow, 2004-5

Membership in Graduate Programs:

  • Biochemistry &Molecular Biology
  • Neurosciences
  • Cell Biology / Cancer Cell Biology
  • Toxicology

For 2nd Life Members – please visit me in my virtual office at UTMB Island Alpha (85, 115, 39)

Research Program

Rapid nongenomic actions of steroids are relevant to many different types of cellular functions and to actions on hormone-responsive cancer cells.  We investigate the actions of both physiological estrogens and estrogen mimetics (xenoestrogens such as environmental estrogens, phytoestrogens, and pharmaceutical estrogens) on the rapid nongenomic signaling cascades initiated by estrogens and other steroids.

We study novel membrane forms of estrogen receptors (mERα, mERß, and GPR30) that mediate nongenomic responses (as opposed to the nuclear versions of estrogen receptors that mediate their action by directly binding to DNA).  In pituitary tumor cells mERα mediates the rapid secretion of prolactin, in part via increases in intracellular calcium entering the cell through L-type calcium channels.  Actions through this membrane estrogen receptor also activate a series of kinases, culminating in activation of the MAP kinases called ERKs.  We have identified cell surface estrogen receptors by immunocytochemically (fluorescence, confocal, and digital image deconvolution microscopy), and via inhibitory antibody and antisense knockdowns of functional responses. The figure below illustrates another type of labeling, due to the binding of a so-called impeded ligand. In this case Estradiol (E2) was conjugated to peroxidase molecules, and the complex bound to the cell surface estrogen receptors on the cell. Then an antibody to peroxidase conjugated to the fluor Cy5 identified these molecules by fluorescence microscopy.(immunocytochemical labeling. A sub-population of GH3 pituitary tumor cells enriched for the membrane estrogen receptor has been selected via immunopanning and limiting dilution subcloning.  The level of membrane estrogen receptors has been correlated with the ability of these cells to rapidly secrete prolactin.

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Membrane estrogen receptors: Cy5 red fluorescent labeling of antibody to the perioxidase identifies peroxidase-E2 conjugates binding to the surface of a GH3/B6 pituitary tumor cells. This is a confocal slice through these cells. The receptor is punctuate and irregularly spaced on cells which are heterogenous for this binding. Hormone, cell density, cell cycle, and the presence of and serum can regulate the expression of this receptor.

 

A functional domain map of the intracellular estrogen receptor-α is shown in the cartoon below.

Functional Domain Map of Intracellular estrogen recepetor alpha
Functional domain map (according to the functions of intracellular ERα): These epitopes are also represented in the membrane estrogen receptor-shown by the symbols at the top of the diagram). The functions of the designated domains in membrane-associated receptors remain to be determined.

We have utilized the ability of these antibodies to recognize mERs to develop a 96-well plate assay to quantify receptors and study their regulation. Xenoestrogens(shown in comparison to 17ß-estradiol in the figure below) also are very potent signaling ligands through the nongenomic response pathway.  Most of them can activate ERK and cause cellular calcium influx via L type channels at picomolar-nanomolar concentrations in pituitary tumor cells.

Xenoestrogens Graphic Other cell types and membrane steroid receptors:

Breast cancer cells (MCF-7) also have membrane estrogen receptors.  In these cells the level of membrane estrogen receptors correlates with the ability of estrogens to activate several signaling cascades which initiate from the membrane and affect cell numbers. More recently we have participated in the demonstration that mast cells respond to both physiological and environmental estrogens via nongenomic signaling mechanisms (with the lab of Dr. Terumi Midoro-Houriuti). Neuronal type cells (PC-12) have all three membrane forms of ERα, ERß. and GPR30.  Xenoestrogens recognize and act via receptors for all these cell types. Collaboratively we have worked with Dr. Bahiru Gametchu on the membrane glucocorticoid receptor which is involved in glucocorticoid-induced therapeutic apoptosis of leukemia and lymphoma cells

Publications -- Current pubmed search

Also see:Watson, C.S.(editor) The Identities of Membrane Steroid Receptors. Kluwer Academic Publishing Co. 2003.

Dr. Watson in 2nd Life (virtual world) visiting the walk-in cell at the 2nd Nature Island
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Last updated: 12/9/2009