Integrins

Malaria is a severe global health problem that causes approximately 435,000 deaths per year. Any non-immune individual traveling to malaria endemic regions can be affected too, including humanitarian volunteers, travelers, and US troops.
Under physiological conditions, damaged or malaria-infected RBCs would be removed within the spleen, but Plasmodium falciparum infected RBCs (iRBCs) sequester to microvascular endothelial cells to avoid entering the spleen. Adhesion interactions and parasite sequestration to endothelial cells are mediated by Plasmodium falciparum erythrocyte membrane protein 1 family (PfEMP1) proteins expressed on the iRBC’s surface. The PfEMP1 proteins bind to existing endothelial cell surface receptors that already serve primary functions, including ICAM-1, integrin αVβ3, and CD36.
Traditionally, these receptors are explored in the context of endothelial cell sequestration, but this project examines the consequence of receptor::PfEMP1 interaction on immune cells, namely monocyte-like THP-1 cells.

Key to our understanding of growth regulation in Drosophila would be discovering a ligand that could regulate steroid synthesis. Activins are involved in regulating steroid hormone release in vertebrates. In invertebrates, they most likely function to keep ecdysone levels low to allow the larvae more time to achieve critical weight in order to initiate the metamorphic process. TGF-B(Transforming Growth Factor Beta) is a family of cytokine growth factors. We find that two members of the TGF-B signaling pathway Drosophila Activin (dACT) and Activin-like ligand Dawdle (DAW) signal through the type I receptor Baboon (BABO) and the type II receptor PUNT to primarily activate the transcription factor dSMAD2 and MAD to a lesser extent. One transcription factor brinker (brk) appears to be central to dACT signaling.

Tumor cells interact with basement membrane collagen at the site of extravasation through distinct cellular receptors, including the α2β1 and α3β1integrins. These receptors are known to be differentially expressed in metastatic tumors, relative to the normal cells, depending on tumor type and stage of progression. The binding sites within type IV collagen for the α2β1 andα3β1 integrins have been identified. Since both of the integinspecific sequences possess at least one glycosylated Hyl residue, we questioned whether glycosylation could modulate integrin binding. Triple-helical peptides with and without Lys substituted by glycosylated Hyl for Lys543 and Lys540 from the human a1(IV)531-543 gene sequence (α3β integrin-specific) and Lys393 from the human a1(IV)382-393 gene sequence (α2β1 integrin-specific) were synthesized and utilized in the present study.