LAB IN THE NEWS
Wistar Receives Support of More Than $5.5M from Private Foundations and Funding Agencies
In the first half of 2018, The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, received funds of more than $5.5 million in grants and awards from local foundations, and national and international funding agencies to support research, education and training at the Institute.
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.
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.
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.
Clayton, K.L., Collins, D.R., Lengieza, J., Ghebremichael, M., Dotiwala, F., Lieberman, J., Walker, B.D. "Resistance of HIV-infected macrophages to CD8+ T lymphocyte-mediated killing drives activation of the immune system." Nat Immunol. 2018 May;19(5):475-486. doi: 10.1038/s41590-018-0085-3. Epub 2018 Apr 18.
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.