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HSCI Science Update: February 2009

February 3, 2009

  • New clues toward understanding chronic GVHD

    Graft-versus-host disease (GVHD) is a common complication of hematopoietic (blood forming) stem cell transplants in which immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. This complication can not only be serious and require lifelong medication but can also sometimes be fatal. HSCI Principal Faculty member Jerome Ritz and colleagues recently further investigated chronic GVHD pathogenesis. Previous experiments suggested a role for a specific type of immune cell, a B cell, in chronic GVHD. Ritz and colleagues pursued the role of B cells in chronic GVHD by characterizing them in patients after they have had hematopoietic stem cell transplants. They found that patients with chronic GVHD had much higher levels of a factor called B cell activating factor (BAFF) as well as of certain types of antibodies. The researchers were then able to delineate specific abnormalities in B cell homeostasis in patients with chronic GVHD. These novel insights into the immunological mechanisms involved in the pathogenesis of chronic GVHD will enable progress toward developing better therapeutics for both prevention and treatment.

    Sarantopoulos, S., Stevenson, K.E., Kim, H.T., Cutler, C.S., Bhuiya, N.S., Schowalter, M., Ho, V.T., Alyea, E.P., Koreth, J., Blazar, B.R., Soiffer, R.J., Antin, J.H., Ritz, J. (2009). Altered B cell homeostasis and excess BAFF in human chronic graft versus host disease. Blood. Jan 23. [Epub ahead of print]

  • Building a heart

    Several of our internal organs, including our heart, intestine, spleen, and liver are shaped asymmetrically and are located asymmetrically in our bodies. Previous studies exploring the left-right asymmetric shape of the heart have implicated the Nodal signaling pathway as being involved, but they have not explained how the pathway has been involved at the cellular level. HSCI Principal Faculty member Alex Schier and colleagues recently explored the role of this pathway in asymmetric heart development in greater detail. Using sophisticated imaging techniques, Schier and fellow researchers discovered that the Nodal pathway functions at a cellular level to drive left-right heart morphogenesis by influencing the speed and direction of cardiomyocytes, a type of heart muscle cell. These findings are significant because they elaborate our understanding of heart development at a detailed level. Understanding the factors that influence the process gives us clues to what may be going awry in the injured or diseased state. Additionally, this expanded knowledge of how the heart develops contributes to our growing toolbox for regenerative medicine approaches which aim to re-grow or replace damaged tissue.

    de Campos-Baptista, M.I., Holtzman, N.G., Yelon, D., Schier, A.F. (2008). Nodal signaling promotes the speed and directional movement of cardiomyocytes in zebrafish. Dev Dyn. 237, 3624-33.