As a recent awardee of the DC CFAR Microgrant Program, the crux of Dr. Amol Kulkarni’s research, which is both collaborative and multidisciplinary in nature, was to develop DNA-dependent protein kinase (DNA-PK) inhibitors specifically for antiretroviral activity. Because HIV transcription is made possible by way of DNA-PK’s interaction with the RNA polymerase II complex employed by the HIV long terminal repeats (LTRs), Dr. Kulkarni, who serves as an Associate Professor in the department of Pharmaceutical Sciences at Howard University, sought to develop DNA-PK inhibitors that are innately designed to suppress HIV gene expression, replication, and reactivation. This Microgrant opportunity presented an avenue to synthesize and characterize compounds that are liable to act as DNA-PK inhibitors while allowing Dr. Kulkarni and his co-investigators to look into interesting molecular targets that could serve as a piece of the HIV/AIDS cure effort.
Given the scope of this project at the time, Dr. Michael Bukrinsky, co-collaborator for this project and Interim Co-Director of the DC CFAR Basic Sciences Core, recommended that Dr. Kulkarni apply for the Microgrant to gather preliminary data. The award allowed Dr. Kulkarni to purchase chemicals and chromatographic supplies that were utilized in the synthesis of four analogs. Designed to provide funding of up to $2,500 to cover the costs of select DC CFAR core services for full investigators, Dr. Kulkarni noted a main benefit of the Microgrant Program is that it can aid in fostering great research ideas that can be strengthened by key experiments for proof of concept. Furthermore, by filling in those gaps, the Microgrant program is well-built and can engender additional NIH funding opportunities – an opportunity that Dr. Kulkarni has established as his next step following this preliminary research project. Dr. Kulkarni hopes to apply for either an R03 or R21 NIH grant, both of which are exploratory and developmental in nature. After garnering additional funding, which could lead to the development of more compounds, Dr. Kulkarni plans to communicate his findings by way of a publication on these HIV-suppressing DNA-PK inhibitors. In addition to developing novel molecules that could aid in the cure for HIV/AIDS, Dr. Kulkarni also hopes to tap into HIV co-morbidities, such as cardiovascular difficulties within HIV infection – to Dr. Kulkarni, it is critical to look beyond the disease itself and instead, delve into “the baggage that it carries”.
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