Tuberculosis remains one of the leading causes of death worldwide. Although, WHO’s latest Global TB Report says that 2018 saw a reduction in the number of TB deaths-an estimated 36% of new TB cases remain undiagnosed or unreported, partly due to the limitations of current diagnostic tools used. Conventional diagnostic tests for microbiological confirmation rely on sputum samples, which can be difficult to obtain and have low diagnostic sensitivity in children, and patients with extrapulmonary TB (EPTB). A major component of the Mycobacterium tuberculosis cell envelope is lipoarabinomannan (LAM), non-covalently associated with the membrane and extends to the exterior of the cell wall. LAM from a culture is heterogeneous in size, branching pattern, acylation, and phosphorylation on the arabinan and mannan portions and has an average molecular weight of 15.4 kilodaltons. With bacterial replication and degradation in the lung, LAM is released, circulating in the blood, filtered across the glomerular basal membrane of the kidneys into urine. We and others have shown that urinary LAM is a viable biomarker for diagnosis of active TB. Many of the recent developments in the structure of LAM in urine, its antigenicity and availability in clinical specimens as a biomarker to develop affordable PoC tests will be presented.
1971-Visva Bharati University, India B.Sc Hons in Organic Chemistry
1973-Visva Bharati University, India M.Sc in Organic Chemistry
1980- University of London, UK, Ph.dCarbohydrate Chemistry, synthesis
1982- York University, Canada , Post Doctoral Fellow in plant polysaccharides
1985-Colorado State University, Post Doctoral Fellow in ID (Mycobacteria)
In the early years, my research had focused on glycomics, glycobiology, genetics and pathogenesis of major cell envelope antigens of M. tuberculosis. I was funded by the WHO and NIH for twenty years. A major portion of this work contributed to our present day understanding of role of lipoarabinomannan (LAM) in pathogenesis. This also provided the premise for investigating LAM as a biomarker for TB Diagnostics today. I have also worked on the metabolomics analysis of granuloma development in the lungs of animals infected with M. tuberculosis and showed for the first time that semi solid NMR i.e. High Resolution Magic Angle spinning (HRMAS) can be applied directly to infected granulomas. I have used Mass Spectrometry and have recently developed methods to analyze oligosaccharides without any use of derivatization. I have successfully administered research projects funded by the NIH, Philanthropic Organizations and Universities, (e.g. recruiting, staffing, research protections, budget), collaborated with other researchers, and produced peer-reviewed publications from each project. I am author or co-author of 130 research papers listed in PubMed. I have been the PI or Co-PI of several NIH research grants, a member of special or ad hoc NIH study sections, all of which dealt with bacterial diseases. Due to recent efforts in our laboratory, we have now developed methods where LAM could be released successfully from complexes in serum and urine, and then detected in subnanomolar concentrations.