I always wanted to become a scientist and discover new theories in Biomedical Sciences as suggested by my grand father who was a distinguished physician. For that purpose, I attended St. Lawrence's School and St. Joseph's College (Microbiology and Chemistry, first position) in Karachi, Pakistan. Then I went to the Karachi University and received a Masters degree in Chemistry (first position). I earned my Ph. D. degree (1975) in Physiological Chemistry (on Biosynthesis of cholesterol, purification and mechanisms of HMG-CoA reductase for the first time) from the University of Wisconsin, Madison, Medical School.
Since then I have worked at the University of Wisconsin (Bacteriology, teaching) and VA Hospital, Madison, WI, for almost 25 years on the mechanisms of drugs for Tuberculosis and bacterial toxins. I developed my project in the year 1980, on the structure of endotoxins from Salmonella and other bacteria. We were successful in getting the structures of the endotoxin and its lipid A components using novel purification techniques and mass spectrometry for the first time. We characterized mono-phosphoryl lipid A, which is one the best known adjuvants for vaccines and cancer. We also characterized lipid A's from several bacteria. We also worked on LPS antagonists.
Then I moved to the University of Missouri as an Associate Professor (Immunology), and Director of Molecular and Cellular Immunology at the Shock/Trauma Research Center in early 2001, where we studied the function of endotoxins and how these cause inflammation and death in the host. We found that endotoxins activate the proteasomes in the cells, causing degradation of several proteins, that affect gene expression and upregulate inflammation. Proteasome inhibitors can block this degradation of proteins and inflammation. Proteasomes are present in all cells and these are dysregulated during sepsis, cancer, diabetes and neurological disorders. We have identified several natural inhibitors and activators of the proteasomes.
We were very fortunate that almost all of our studies over the past 50 years were funded by the National Institutes of Health (NIH). We worked with medical and Ph.D. students, MD's, post-docs, technicians, 40 collaborators around the world, and published over 180 manuscripts in good journals. We have received several awards for our studies. We are grateful to NIH for supporting our biomedical research. I would like to thank NIH and all the co-workers that have worked on our projects and helped with my empowerment. Presently, I am working on publishing more manuscripts as Professor Emeritus at the University of Missouri, Kansas City, and as a consultant.
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