The problem is that the peptides are derived from proteins expressed in normal skin cells. Using mice, whose immune systems have been humanized, Colella is trying to figure out if the T-cells can distinguish the peptide antigens on melanoma cells as foreign even though the proteins from which they are derived are normally expressed in the skin. She has discovered that the enzyme tyrosinase, essential for normal skin pigmentation, limits the immune response to the tyrosinase-derived melanoma antigen. Colella and her colleagues have found that when they remove tyrosinase from mice, the immune system responds much better to fighting the melanoma cells. They are now trying to decipher how tolerance to tyrosinase is maintained, and they are testing slightly modified versions of the tyrosinase peptide vaccine in mice that express tyrosinase to see if the immune system's tolerance can be overcome, so that the T-cells can be activated to destroy the melanoma cells.
Research can be frustrating, but it is also exciting.
She hopes to combine her interests in vaccine research and public health.