Research Focus 1

The general research topic:
Blood cell development. An overview of blood cell development is given on the Research Focus Page 2

The major question we address: What molecular mechanisms determine the fate of developing blood cells? Why and how does a particular cell choose to become an erythrocyte, for example, rather than a granulocyte?

Our research approach: We have developed two strategies for analyzing the growth and differentiation of blood cells. One utilizes an in vitro cell system (shown below, left) composed of the myeloid progenitor cell line, FDC-P1, expressing the M-CSF receptor, Fms, from a retroviral vector. The FD-Fms cells simply reproduce without change in response to the growth factor IL3, but differentiate to macrophages in M-CSF. The second system we employ is the in vivo transgenic and knockout model in mice (below, right).

Recent results: We have written two recent reviews that each cover one of the main topics in signal transduction we currently study in the Fms pathway. The references are:
Bourette, R.P. and L. R. Rohrschneider. Early events in M-CSF Receptor Signaling. Growth Factors17:156-166, 2000.
Rohrschneider. L.R., Fuller, J.F., Wolf, I., Liu, Y., and Lucas, D.M., Structure, Function, and Biology of SHIP Proteins. Genes & Develop.14:505-520, 2000.

Future directions: Our future direction in research will continue to characterize and clone proteins in the Fms pathway. A few additional proteins have been identified and we hope to clone these. So far, mainly early events in signaling have been studied, but future work will focus more and more on later events within the nucleus. A major task then becomes understanding the assembled components and arranging these in understandable networks. Deep within this problem, we are optimistic that an understanding will emerge of how a blood cell functions in the regulation of growth and differentiation.

What is the expected significance from such studies?: I think the main significance (at least the one NIH would like to hear) is that these results will tell us how a normal blood cell functions, and why a cell can "forget or lose" its normal regulatory mechanisms causing so much anguish to the person that carries that cell. Cancer is perhaps the most prominent example, and blood cells at any stage of development can lose that balance between growth and differentiation and thus become a leukemia. A second aspect relates to the natural human curiosity for exploring our unknown, and life is perhaps one of the greatest unknowns we presently face.

The general research topic:	Blood cell development. An overview of blood cell development is given on the Research Focus Page 2
The major question we address:	What molecular mechanisms determine the fate of developing blood cells? Why and how does a particular cell choose to become an erythrocyte, for example, rather than a granulocyte?
Our research approach:	We have developed two strategies for analyzing the growth and differentiation of blood cells. One utilizes an in vitro cell system (shown below, left) composed of the myeloid progenitor cell line, FDC-P1, expressing the M-CSF receptor, Fms, from a retroviral vector. The FD-Fms cells simply reproduce without change in response to the growth factor IL3, but differentiate to macrophages in M-CSF. The second system we employ is the in vivo transgenic and knockout model in mice (below, right).
Recent results:	We have written two recent reviews that each cover one of the main topics in signal transduction we currently study in the Fms pathway. The references are: Bourette, R.P. and L. R. Rohrschneider. Early events in M-CSF Receptor Signaling. Growth Factors17:156-166, 2000. Rohrschneider. L.R., Fuller, J.F., Wolf, I., Liu, Y., and Lucas, D.M., Structure, Function, and Biology of SHIP Proteins. Genes & Develop.14:505-520, 2000.
Future directions:	Our future direction in research will continue to characterize and clone proteins in the Fms pathway. A few additional proteins have been identified and we hope to clone these. So far, mainly early events in signaling have been studied, but future work will focus more and more on later events within the nucleus. A major task then becomes understanding the assembled components and arranging these in understandable networks. Deep within this problem, we are optimistic that an understanding will emerge of how a blood cell functions in the regulation of growth and differentiation.
What is the expected significance from such studies?:	I think the main significance (at least the one NIH would like to hear) is that these results will tell us how a normal blood cell functions, and why a cell can "forget or lose" its normal regulatory mechanisms causing so much anguish to the person that carries that cell. Cancer is perhaps the most prominent example, and blood cells at any stage of development can lose that balance between growth and differentiation and thus become a leukemia. A second aspect relates to the natural human curiosity for exploring our unknown, and life is perhaps one of the greatest unknowns we presently face.