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Faculty Profile

First Name: 
Steven
Last Name: 
Collins
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Primary Institution: 
FHCRC
Department/Division: 
Human Biology
Department/Division: 
other
E-Mail: 
Mail/Box #: 

C2-023

Office Location: 

C2-159

Office Phone: 
(206) 667-4389
Research

Research Summary: 

Our laboratory studies the molecular pathogenesis of human myeloid leukemia. Our recent observations indicate that a particular calcium regulated enzyme- CaMKIIgamma- is a critical regulator of myeloid leukemia cell proliferation. We have found that this enzyme directly phosphorylates the retinoic acid receptor and inhibits its transcriptional activity. The activated (autophosphorylated) CaMKII is present in 100% of myeloid leukemia cell lines, and levels of the activated CaMKII are markedly diminished in leukemia cells undergoing terminal differentiation /apoptosis. Inhibiting CaMKII utilizing pharmacological agents, dominant negative constructs or shRNA vectors inhibits myeloid leukemia cell proliferation, and this is associated with the inactivation / downregulation of a number of important phosphoprotein signaling networks involving the MAP kinase, JAK/Stat and GSK3beta / beta-catenin pathways. Our current experimental efforts are focused on: (1) identifying the critical substrates of CaMKII in myeloid leukemia cells; (2) defining the molecular mechanisms that regulate the calcium-mediated CaMKII activation in myeloid leukemia with an emphasis on the role that plasma membrane calcium channels play in this activation; (3) determining the clinicopathological significance of activated CaMKII in primary human AML cells; and (4) identifying small molecule inhibitors of the Ca++ channels that potentially could be useful in the therapy of myeloid leukemia.

Short Research Description: 
calcium regulation of leukemia cell proliferation
Areas of Interest: 
Cancer Biology
Cell Signaling & Cell/Environment Interactions
Keywords: 
<p> nuclear hormone receptors, retinoic acid receptors, hematopoiesis, leukemia cell differentiation, Stat proteins, calcium signaling,calcium channels</p>
Publications


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