By Leah Mann
Md. Jashim Uddin, research associate professor of biochemistry, has received a 2022 National Project Research Grant from Phi Beta Psi. Uddin was one of six recipients nationally and is the first-ever Vanderbilt faculty member to receive this award. The Phi Beta Psi Sorority is a national civic organization whose members are committed to charitable work and fighting against cancer.
Uddin’s funded project* seeks to advance diagnostic efforts, focusing on the use of a nanotechnology-based probe to enable early detection of colorectal cancer. The goal is to employ nanotechnology in the molecular endoscopic visualization of colon cancer, an aim that builds on recent research he published in ACS Chemical Biology.
That paper, published this summer, describes a new probe called fluorocoxib Q, or FQ, which Uddin developed along with fellow researchers in the laboratory of Lawrence Marnett, Mary Geddes Stahlman Professor of Cancer Research and University Distinguished Professor of Biochemistry and Chemistry. The new probe that can be used to distinguish pathological or diseased cells from other, healthy cells, was key to getting the Phi Beta Psi award.
COX-2, the enzyme targeted by the probe, is involved in the synthesis of prostaglandins, which facilitate inflammation. Accordingly, COX-2 is overexpressed in inflamed and neoplastic (abnormally growing) tissues while absent in normal tissues. Thanks to its role in pathogenesis, COX-2 is a promising molecular target for detecting pathological cells and strengthening diagnostic imaging.
Previous work suggests that COX-2 activity is associated with the production of reactive oxygen species, or ROS, which in turn increases the oxidation in the environment. Extending earlier work with COX-2-targeted radiological and optical imaging agents, Uddin and Marnett have now developed a “redox-activatable” imaging agent that specifically binds to COX-2 and is only detectable in the presence of ROS.
The team of Vanderbilt scientists evaluated the potential of FQ in both cultured cancer cells and a mouse model of inflammation and established that the use of FQ resulted in higher specificity and less background noise when visualizing pathogenesis compared to other agents.
This new probe is the focus of Uddin’s Phi Beta Psi award, which will allow him to evaluate the use of FQ—encapsulated in a variety of nanoparticles—to use endoscopic optical imaging to detect colonic adenomas, a type of pre-cancerous tumor of the colon. Moreover, he will use the funds to verify that FQ fluoresces specifically in the presence of COX-2 and ROS in colorectal carcinogenesis.
The development of FQ, as well as Uddin’s planned work with the nanoparticles, will create a framework for using the presence of COX-2 and ROS as biomarkers of neoplasia in the colon and will facilitate the development of the nanotechnology for the early detection, margin delineation, and surgical removal of colorectal cancer in patients.
*Uddin’s grant proposal was supported by Research Development and Support, which offers proposal development assistance for both private (foundations) and federally funded opportunities. Services include searches for new sponsors, coordination and team building for proposals of any size, content development, and draft review. RDS further supports faculty by building relationships with external sponsors, hosting workshops, and providing guides and language for common proposal requirements. RDS is in the Office of the Vice Provost for Research and Innovation. To learn more about RDS or request services, contact them at rds@vanderbilt.edu.
Go Deeper
The article by Uddin M. J. et al. “Discovery of a Redox-Activatable Chemical Probe for Detection of Cyclooxegenase-2 in Cells and Animals” was published in ACS Chemical Biology in July 2022.