Donald Branch,

• Signaling involving c-Src
• Signaling abnormalities in malignancies
• Signaling in HIV/AIDS pathogenesis and disease resistance
• Studies on mechanism of Rh immune prophylaxis and other IVIg prophylatic therapies
• Red cell senescence and hemolytic anemias

Dr. Branch investigates the biochemical signals that tell cells what to do- whether to grow, die or fight infection, and whether they can be infected by pathogens, such as viruses. He aims to understand the pathogenesis and functioning of cells in various diseases that require blood transfusion products. Understanding the molecular defects that may occur in certain diseases could lead to new treatments or cures and could help to alleviate some of the transfusion requirements for these patients. Dr. Branch's research on mononuclear phagocytes, includes studies to understand how these cells function in autoimmune diseases, to try to develop new strategies to treat these blood diseases.

Dr. Branch's lab has identified at least three new targets for HIV/ Acquired Immune Deficiency Syndrome (HIV/AIDS) therapy. His team is continuing these studies to determine the potential efficacy of animal and/or human studies to determine if these new targets can be successfully used for treatment modalities. The team has described a new approach to vaccine development that could eventually result in the provision of necessary immunity to the vast population of people exposed to HIV. Dr. Branch's research also involves the study of signal transduction. He is interested in the Src family of protein tyrosine kinases and the SHP-1 protein tyrosine phosphatase. His lab has recently identified c-Src protein expression in primary human B cells following activation to a proliferative state and has shown that c-Src expression correlates directly with this proliferation and may be required. His lab has shown that SHP-1 acts as a tumor suppressor protein in hematopoietic cells and that abnormal forms of this protein produced through alternative-splicing may be involved in breast and other epithelial cancers.

His lab has identified a neuroendocrine receptor family, known as VPAC, which has one member, VPAC1, that binds to HIV and signals to facilitate the infection and another, VPAC2, that can be externally activated to send an inhibitory signal to stop HIV infection.

Dr. Branch has identified a novel mechanism of action for IVIg, the induction of interleukin(IL)-11. This discovery has led to his proposing a unifying theory of IVIg-induced IL-11 to explain all clinical effects of IVIg treatment.

Selected Publications:

Wang, Q., Rajshankar, D., Branch DR, Abreu, M.T.H., Downey, G.P. and McCulloch, C.A.: Protein tyrosine phosphatase-a and Src functionally link focal adhesions to the endoplasmic reticulum to mediate IL-1 signaling. J. Biol. Chem. 2009; 284:20763-20772.

Cayer, M-P., Proulx, M., Ma, X-Z., Sakac, D., Giguere, J-F., Drouin, M., Neron, S., Branch DR, and Jung, D. c-Src tyrosine kinase co-associates with and phosphorylates STAT5b which mediates the proliferation of normal human B lymphocytes. Clin Exp Immunol 2009; 156:419-427.

Lund, N., Olsson, M.L., Ramkumar, S., Sakac, D., Yahalom, V., Levene C., Hellberg, Å., Ma, X-Z., Binnington, B., Jung, D., Lingwood, C.A. and Branch DR: The human Pk histo-blood group antigen provides protection against HIV-1 infection. Blood 2009; 113:4980-4991.

Kruspe, A., Katsman, Y., Sakac, D., Chagneau, C., Glistvain, A., Langler, R.E., and Branch DR: Reduction of disulfide bonds within anti-D results in enhanced Fc? receptor blockade. Transfusion 2009; 49:928-936.

Branch DR.: Gender-selective toxicity of thimerosal. Exp. Toxicol. Path. 2009; 61:133-136.

Ramkumar, S., Sakac, D., Binnington, B., Branch, D.R., and Lingwood, C.A: Induction of HIV-1 resistance: cell susceptibility to infection is an inverse function of globotriaosyl ceramide levels. Glycobiol. 2009; 19:76-82.