Research Projects

Tuberculosis (TB) continues to be the world’s deadliest infectious disease, annually causing over a million fatalities and affecting millions more, leaving devastating social and economic impacts on communities worldwide. The global fight against TB is complicated by the alarming rise of drug-resistant strains, particularly multidrug-resistant TB (MDR-TB), where Mycobacterium tuberculosis (Mtb) becomes resistant to key first-line drugs like isoniazid and rifampin. In recent years, extensively drug-resistant TB (XDR-TB) has emerged, posing even greater challenges as it shows resistance to additional drug classes, leading to treatment regimens that are complex, costly, and often less effective. Given the limited efficacy and side effects associated with existing TB therapies, there is an urgent need to discover novel anti-TB agents, particularly those that employ new mechanisms of action to outpace bacterial resistance. Addressing this critical gap, my research program will focus on identifying compounds that act on dual biological pathways within Mtb, targeting energy metabolism with a particular emphasis on oxidative phosphorylation. Oxidative phosphorylation, a central pathway in the bacterial energy production process, presents a promising target, as its inhibition can effectively disrupt Mtb survival. This approach has gained momentum in recent research, as inhibiting energy metabolism could significantly weaken the bacterium’s resistance mechanisms, making it more susceptible to therapeutic intervention. To achieve this, I propose an integrated approach leveraging drug synergism where two or more compounds work together to enhance their effects by combining drugs that target different essential pathways in Mtb. This strategy aims not only to inhibit bacterial growth but also to minimize the likelihood of resistance development, as it forces Mtb to counteract multiple mechanisms simultaneously. My expertise in organic synthesis, medicinal chemistry, and chemical biology will play a crucial role in designing and optimizing such compounds. The research program will benefit from a synergistic collaboration between academia and industry, pooling resources and expertise from synthetic and medicinal chemists. Recent studies have demonstrated the value of such collaborations in accelerating drug discovery and translating laboratory findings into clinical applications. By working across academic and industrial environments, we can enhance both the innovation and practical application of new anti-TB therapeutics, ultimately contributing to the global health landscape by offering effective treatment options with fewer side effects. This collaborative effort holds promise for advancing TB research and improving treatment outcomes for one of the world’s most pressing public health challenges.