Discovery of Functional Protein Interactions in Human Diseases
Renata Pasqualini, Ph.D. and Wadih Arap, M.D., Ph.D.
As a matter of record, we have a long-standing collaboration and have led a joint laboratory since October 1999. Since our arrival at The University of Texas MD Anderson Cancer Center, we have jointly published more than 100 original peer-reviewed research manuscripts and, with very few exceptions, such publications are a team science effort. Our research group currently includes graduate or M.D./Ph.D. students, postdoctoral fellows, faculty (assistant and associate professors), research technicians, and administrative staff members.
The central working hypothesis in this program is that differential protein expression in the human vascular endothelium associated with normal or diseased tissues offers the potential for developing novel diagnostic, imaging and therapeutic strategies. In essence, combinatorial library selections (peptide- and antibody-based) are leveraged to discover, validate and exploit the vascular biochemical diversity of endothelial cell surfaces towards a new vascular-targeted pharmacology. Such targeting technologies may lead to the development of ligand-directed agents for application in the treatment of patients with cancer.
Translational applications, such as first-in-human clinical trials, have now began within the institution, as the Food and Drug Administration (FDA) has recently granted a “safe-to-proceed” status for the first vascular-targeted Investigational New Drug, which was discovered, developed and is being evaluated in patients at MD Anderson. Such trials will ultimately determine the value of this strategy. Two other drugs are in pre-IND stage and several others are in pre-clinical laboratory phase. Long term, the broader vision of the research is a large-scale mapping of receptors in human vasculature towards a new ligand-directed pharmacology.