UPENN SOM || Cultural Competency Medical Education Program || Eric Russell, MD

Eric Russell, MD

Eric Russell, MD, has a major research effort in the Russell laboratory is directed towards defining the properties of hemoglobins that incorporate embryonic globin subunits. The impetus for this activity is the possibility that these hemoglobins might subserve therapeutically valuable roles in adults with disorders of globin gene expression, such as thalassemias or sickle cell anemia. Using complex transgenic/knockout mice as bioreactors we have generated and purified each of these unusual human hemoglobins and established many of their basic properties. Ongoing experiments are designed to evaluate the anti-sickling properties of these hemoglobins, their important biochemical characteristics, and their physiological role in human development.

A second major research effort is directed towards understanding the molecular mechanisms that contribute to the developmental silencing of embryonic globin genes. We have found that full silencing of the z-globin gene in adults requires post-transcriptional events that regulate z-globin mRNA stability. In more recent work we have established important structural and functional links between the mechanisms that stabilize the a- and b-globin mRNAs. Our current investigations focus on the mechanisms through which the e-, g-, and b-like globin mRNAs are stabilized, as well as the possibility that these properties are actively regulated to optimize function of the mature erythrocyte. A thorough understanding of these mechanisms would permit the design of therapies intended to dysregulate globin gene expression through manipulation of mRNA stability.

In addition to studies relating to globin gene expression and function, we have initiated a series of pilot experiments focused on establishing the mechanism through which the prothrombin 3'UTR G20210A mutation effects hyperprothrombinemia. New investigators would be encouraged to participate in ongoing research, or to design new projects relating to our interests in the post-transcriptional control of globin gene expression or the function of embryonic globins.