Research Description:
The Grunwald laboratory uses zebrafish to uncover and study the molecular basis of a variety of human diseases and congenital defects. Current 2010 summer research projects include:
1) Investigation of the role of calcium mobilization in the Hedgehog growth factor signaling pathway. Hedgehog (Hh) is a secreted growth factor involved in intercellular communication. It has major roles in regulating the patterning of the developing limb and spinal cord and in regulating the development of stem cells. Thus partial or complete loss of Hh function is associated with birth defects, including holoprosencephaly, and aberrant Hh function is associated with cancers, notably basal cell carcinoma and medulloblastoma. Our group has recently shown that controlled intracellular calcium release is required for a cell to respond to Hh. The project is aimed at understanding what role calcium plays in carrying out the Hh response and whether inhibition of calcium release can be used to manipulate Hh signaling in all cases.
2) Investigation of the role of Selenoproteins in heart development and function. Cardiac myopathy is a serious and prevalent health problem. Our recent studies indicated that Selenoproteins play a necessary role in the differentiation and function of skeletal muscle. Loss of Selenoprotein N causes congenital skeletal myopathies in humans. Our work in the zebrafish uncovered the function of Selenoprotein N, showing that it is a necessary co-factor of the skeletal muscle intracellular calcium release channel (RYR1) acting to sense redox signals and regulate calcium flow. As cardiac myopathy is linked to redox stress, we propose there are mechanisms for sensing and responding to redox signals in heart muscle. We hypothesize that the cardiac muscle intracellular calcium release channel (RYR2) is also associated with a selenoprotein that has an analogous function to that of Selenoprotein N. This study will use antisense methods to test the functions of a small number of sel
enoproteins expressed in the embryonic heart.
Does this research involve human subjects or animals? Yes
If yes, what is the protocol number? 08-01007
11/2009
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