LAB IN THE NEWS
TP53 Genetic Variant Found in Individuals of African Descent is Linked to Iron Overload but May Improve Response to Malaria
Iron accumulation and defects in the antibacterial function of macrophages caused by the P47S variant result in a less severe inflammatory response.
Immuno-antibiotics: A New Frontier in the Fight Against Antimicrobial Resistance
Have you ever taken antibiotics for a sore throat and ended the treatment as soon as the symptoms disappeared and without finishing the course of medicine? This is a common mistake many of us have made and just one example of the many antibiotic misuses and over-uses that have led to the developm
The Dotiwala Laboratory
The Dotiwala laboratory uses cellular, molecular, biochemical and omics approaches, as well as sophisticated in vivo imaging, to dissect the mechanism by which cell-based immunity (neutrophils, macrophages and killer lymphocytes) is activated in the presence of different pathogenic bacteria, such as intra- and extracellular bacteria, fungi and protozoa. In particular, they investigate how killer immune cells use pore forming protein perforin, antimicrobial peptide granulysin, and immune protease granzyme B in synergy to destroy pathogens in host cells. The ultimate goal of this research is to adapt different immune proteases coupled with antimicrobial peptides as therapies for drug-resistant bacterial infections. The lab is also interested in delivering immune proteases to cancer cells to restrict their ability to develop resistance.
Sachin Singh, Ph.D.
Singh, K.S., Sharma, R., Narayana Reddy, P.A., Vonteddu, P., Good, M., Sundarrajan, A., Choi, H., Muthumani, K., Kossenkov, A., Goldman, A.R., Tang, H., Totrov, M., Cassel, J., Murphy, M., Somasundaram, R., Herlyn, M., Salvino, J.M., Dotiwala, F. "IspH inhibitors kill Gram-negative bacteria and mobilize immune clearance" Nature. 2020 Dec 23. doi: 10.1038/s41586-020-03074-x.
Sachin Singh, K., Leu, J., Barnoud, T., Vonteddu, P., Gnanapradeepan, K., Lin, C., Liu, Q., Barton, J., Kossenkov, A., George, D., Murphy, M., Dotiwala, F. "African-centric TP53 Variant Increases Iron Accumulation and Bacterial Pathogenesis but Improves Response to Malaria Toxin." Nat Commun. 2020 Jan 24;11(1):473. doi: 10.1038/s41467-019-14151-9.
Dotiwala, F., Sen Santara, S., Binker-Cosen, A.A., Li, B., Chandrasekaran, S., Lieberman, J. "Granzyme B Disrupts Central Metabolism and Protein Synthesis in Bacteria to Promote an Immune Cell Death Program." Cell. 2017 Nov 16;171(5):1125-1137.e11. doi: 10.1016/j.cell.2017.10.004. Epub 2017 Oct 26.
Basu, R., Whitlock, B.M., Husson, J., Le Floc'h, A., Jin, W., Oyler-Yaniv, A., Dotiwala, F., Giannone, G., Hivroz, C., Biais, N., et al. "Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing." Cell. 2016 Mar 24;165(1):100-110. doi: 10.1016/j.cell.2016.01.021. Epub 2016 Feb 25.
Dotiwala, F., Mulik, S., Polidoro, R.B., Ansara, J.A., Burleigh, B.A., Walch, M., Gazzinelli, R.T., Lieberman, J. "Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites." Nat Med. 2016 Feb;22(2):210-6. doi: 10.1038/nm.4023. Epub 2016 Jan 11.