The Development and Characterization of Monoclonal Antibodies for Integrins and TGF-b
Mentor: Tim Springer, Ph.D. (Boston Children's Hospital)
Integrins, of which are made up of both an a and a b subunit, comprise a group of 24 cellular adhesion receptors. This family of transmembrane receptors plays several key roles in regulating a variety of cellular functions, many of which are vital to the development and advancement of cancer. As such, integrins have been heavily investigated as potential immuno-oncology targets in research. In the Springer Lab, we will be focusing on characterizing integrin a and b subtype-specific antibodies. Such antibodies could be used to regulate and better understand the key functions of integrins, including the role they play in cancer progression and metastasis. Furthermore, we are also interested in the signaling between integrins and transforming growth factor b (TGF-b). TGF-b is a multifunctional cytokine that controls immune responses, suppresses anti-tumor immunity, and is strongly associated with a poor prognosis for cancer patients. A newly discovered molecule named leucine-rich repeat containing protein 33 (LRRC33) has been found to present TGF-b for activation by integrins avb6 and avb8. At the Springer Lab, we will be using interdisciplinary approaches, including molecular cloning, flow cytometry, and western blotting, to identify and select high-sensitivity and high-specificity monoclonal antibodies that can disrupt such cellular signaling pathways. Through this research project, we are aiming to develop anti-integrin and anti-TGF-b monoclonal antibodies, of which will be useful in understanding the complexity of these molecules are their roles in cancer.
The figure shown above reveals the structure and activation mechanism of the latent TGF-b1 procomplex. The image highlights how the latency associated peptide forms a ring that prevents the 110-residue growth factor from interacting with cellular receptors and participates in its activation through interactions with various integrins. Source: