Combinatorial chemical synthesis and biological screens are extremely important in therapeutic and diagnostic agent developments. We apply several types of combinatorial techniques; (A) to identify high affinity and high specific peptidomimetic compounds targeting cancer cell surface receptors, as well as (B) to study and develop better contrast agents.
|
|||||||||||||||
D. Gomika Udugamasooriya, Ph.D.
Research Overview
The development of early detection strategies, efficaous treatments, and reliable monitoring methods are major challenges
in oncology. Many of the conventional methods used to detect and treat cancer have only generated limited results due to
the complexity of the disease as well as un-optimized and non-specific activity of current diagnostic and therapeutic agents.
A meaningful impact on cancer screening, staging, and treatment is not likely to occur until the affinity and specificity
of these agents for cancer cells are increased significantly over that of normal cells. To overcome this problem, my lab
aims to develop and evaluate high affinity and specific multi-site binding peptidomimetic ligands for cancer cells via a
genome-wide target search as well as an unbiased selection approach. Identified ligands can later be used as therapeutic
agents as well as imaging agent carriers in the clinic. We also focus on developing better contrast agents through combinatorial
approaches.
The main approaches use in my lab achieving these goals are:
- Explore biologically amenable novel classes of peptidomimetics (in particular peptoids) and develop diverse set of chemical libraries with millions of permutations.
- Identify best candidates out of these combinatorial libraries. We have already developed an on-bead two-color cell screening
technology that allows direct identification of highly specific ligands. These novel compounds will be indentified through 2 basic approaches:
- Targeting known cancer cell surface receptors (selected using the genome-wide m-RNA/protein expression data base available on campus),
- Through unbiased selection (targeting both known and unknown biomarkers on cancer cell surface over normal cells).
- Further develop/optimize those lead compounds (multimerizations, minimum phramacophore identifications, further improvements via various structural modifications).
- Validate binding, therapeutic and imaging agent delivering potentials of those lead compounds.
- Apply combinatorial principles to study, identify and further optimize novel contrast agents for MRI and PET imaging applications.
This lead compound development process is compliant with many cancer types such as lung, breast, prostate etc., developing global set of tools to detect, monitor and treat cancer, leading to develop personalized medication systems in the future. Combinatorial and parallel solid phase synthesis, on-bead cell screen, cell binding and functional assays and targeted imaging are some of the main techniques used in my lab. Overall, these projects cover chemical synthesis to biological investigation and ultimately address both diagnostics and therapeutic aspects of cancer medicine. This offers students/ fellows a unique opportunity to learn the "development" as well as the "application" sides of lead compound evolution process in a true chemical biology environment.
Contact email: gomika.ugudama@utsouthwestern.edu
Research Interests
| Peptidomimetics (in particular peptoids) development | Combinatorial synthesis and cell screen |
| Cancer therapy-diagnostic tool development - “Theranostics” | Novel contrast agent development |
| Personalized medicine |
© The University of Texas at Dallas
