The main focus of Dr. Velu’s lab is drug discovery and development. Lab work force is mainly constituted of graduate students working towards their PhD degree, undergraduate students carrying out their senior / honors research, postdoctoral trainees and occasionally research assistants. The research projects are mainly directed towards the discovery of anti-cancer and anti-infective agents. The ongoing research projects are:
Small molecule inhibitors of cariogenic biofilms
Current methods to prevent dental caries use conventional oral hygiene practices, such as frequent tooth brushing and the use of oral mouth rinses. However, such treatments are ineffective because of the rapid re-colonization of bacteria and the biofilm nature of caries making the cariogenic bacteria resistant to traditional anti-microbial treatments. We target virulence factors of Streptococcus mutans, the major etiological agent for dental caries to discover specific biofilm inhibitors with potent anti-caries activity.
Marine Alkaloid Analogs for Breast Cancer Therapy
In spite of the recent advances in computational approaches for lead identification and drug discovery, natural products remain as an important source for novel anticancer agents. In addition, natural products provide drugs with unprecedented molecular structures and bioactivity that are often inaccessible by other methods, and provide templates for future drug design. Our laboratory has focused recent research on the development of novel marine natural products and their analogs for human breast cancer therapy.
Staphylococcus aureus Sortase A inhibitors
As bacterial pathogens develop resistance to conventional antibiotics, inhibition of bacterial surface protein display offers a novel strategy against S. aureus bacterial infections. By interrupting bacterial adherence, the initial step in the pathogenesis of bacterial infections, S. aureus will be poorly equipped to cause the disease and may be more effectively cleared by host innate immune defenses and/or by antibiotics. We hypothesize that the inhibitors of the surface enzyme, sortase will render S. aureus non-adherent and consequently less virulent.
Trypanosoma Cruzi DHFR inhibitors
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. Since the dihydrofolate reductase activity of T. cruzi (TcDHFR) is essential for the parasite, it represents a potential target for the rational drug design for Chagas disease. In order to design selective inhibitors of TcDHFR we have initiated a structure based drug design using the X-ray crystal structure of T. cruzi DHFR. Subtle differences in the active sites of TcDHFR and hDHFR are taken in to consideration for the design selective TcDHFR inhibitors.
Voltage Gated Sodium Channel Blockers
The ability to prevent or slow down metastasis would represent a major breakthrough in cancer therapy and dramatically improve life expectancies of cancer patients. Fortunately, our increasing understanding of the metastatic process has recently resulted in the discovery of new potential drug targets to prevent / slow metastasis. One such target is the voltage-Gated Sodium Channels (VGSC). This project is directed towards targeting VGSCs for developing drugs that prevent / slow down breast and prostate cancer metastasis.