Farokh Dotiwala, M.B.B.S., Ph.D.

Farokh Dotiwala, M.B.B.S., Ph.D.

Laboratory

The Dotiwala Laboratory

Contact

215-495-6897
fdotiwala@wistar.org

Assistant Professor, Vaccine & Immunotherapy Center

About the Scientist

Dotiwala studies the mechanisms by which cell-based innate and adaptive immunity destroy diverse non-viral pathogens, with the aim of applying these mechanistic insights to aid in designing better antimicrobial and anti-cancer therapies.

Dotiwala received an M.B.B.S. in Medicine from Grant Medical College, Mumbai, India, and a Ph.D. in Molecular and Cell Biology from Brandeis University. He was a postdoctoral research fellow at Harvard University and an Instructor in Pediatrics at Boston Children’s Hospital and Harvard Medical School, before joining Wistar as an assistant professor in 2017.

View Publications

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.

Staff

Postdoctoral Fellow

Sachin Singh, Ph.D.

Research Assistant

Prashanthi Vonteddu

Selected Publications

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., Lieberman, J., et al. "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., Lieberman, J., Kam, L.C., Huse, M. "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., Lieberman, J., et al. "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.

Walch, M., Dotiwala, F., Lieberman, J., et al. "Cytotoxic Cells Kill Intracellular Bacteria through Granulysin-Mediated Delivery of Granzymes." Cell. 2015 May 21;161(5):1229. doi: 10.1016/j.cell.2015.05.021. Epub 2015 May 21.

View Additional Publications