Bindra Lab (Yale University)
- E.D. Huseman, A. Lo, O. Fedorova, J.L. Elia, S.E. Gueble, K. Lin, R.K. Sundaram, J. Oh, J. Liu, F. Menges, M.G. Rees, M.M. Ronan, J.A. Roth, V.S. Batista, J.M. Crawford, A.M. Pyle, R.S. Bindra, S.B. Herzon. Mechanism of Action of KL-50, a Candidate Imidazotetrazine for the Treatment of Drug-Resistant Brain Cancers. Journal of the American Chemical Society. 30 May 2024.
- Over half of glioblastoma, a deadly brain cancer, do not express methylguanine methyltransferase (MGMT), an important DNA direct repair enzyme. Tumors lacking MGMT are more sensitive to specific kinds of DNA damage, however, resistance often arises by loss of mismatch repair (MMR), which senses this specific DNA damage and leads to cell death. The Bindra and Herzon Labs developed KL-50 as a novel DNA-damaging agent that is selectively toxic to MGMT-deficient cells regardless of MMR status (Lin and Gueble et al.). Here, we elucidate the mechanism of the molecule in detail and offer chemical explanations for its apparent superiority over a similar DNA-damaging agent, mitozolomide (MTZ). I acted as the cell biology lead on the project.
- Over half of glioblastoma, a deadly brain cancer, do not express methylguanine methyltransferase (MGMT), an important DNA direct repair enzyme. Tumors lacking MGMT are more sensitive to specific kinds of DNA damage, however, resistance often arises by loss of mismatch repair (MMR), which senses this specific DNA damage and leads to cell death. The Bindra and Herzon Labs developed KL-50 as a novel DNA-damaging agent that is selectively toxic to MGMT-deficient cells regardless of MMR status (Lin and Gueble et al.). Here, we elucidate the mechanism of the molecule in detail and offer chemical explanations for its apparent superiority over a similar DNA-damaging agent, mitozolomide (MTZ). I acted as the cell biology lead on the project.
- E.D. Huseman, A. Lo, O. Fedorova, J. Elia, S. Gueble, K. Lin, R. Sundaram, J. Oh, J. Liu, F. Menges, M. Rees, M. Ronan, J. Roth, V. Batista, J. Crawford, A. Pyle, R. Bindra, S. Herzon. Mechanism of Action of KL-50, a Novel Imidazotetrazine for the Treatment of Drug-Resistant Brain Cancers. ChemRxiv. 13 June 2023.
- Preprint. See above manuscript for final version and description.
Rotello Lab (UMass Amherst)
- D.C. Luther, R. Goswami, Y-W. Lee, T. Jeon, R. Huang, J.L. Elia, H. Nagaraj, J.J.E. Bijlsma, M. Piest, M.A. Langereis, V.M. Rotello*. Non-viral vaccination through cationic guanidium polymer-pDNA polyplex mediated gene transfer. Nanoscale. 30 May 2023.
- We used the PONI cationic homopolymer (described below) to deliver plasmid DNA directly to the cytosol, generating an immune response in vitro. Then, we used this system to successfully vaccinate chickens against Newcastle Disease, a lethal viral infection.
- We used the PONI cationic homopolymer (described below) to deliver plasmid DNA directly to the cytosol, generating an immune response in vitro. Then, we used this system to successfully vaccinate chickens against Newcastle Disease, a lethal viral infection.
- T. Jeon, D.C. Luther, R. Goswami, C. Bell, H, Nagaraj, Y.A. Cicek, R. Huang, J.A. Mas Rosario, J.L. Elia, J. Im, Y-W. Lee, Y. Liu, F. Scaletti, M.E. Farkas, J. Mager, V.M. Rotello*. Engineered Polymer-siRNA Polyplexes Provide Effective Treatment of Lung Inflammation. American Chemical Society Nano. 14 Feb 2023.
- D.C. Luther, Y. Lee, H. Nagaraj, V. Clark, T. Jeon, R. Goswami, S. Gopalakrishnan, S. Fedeli, W. Jerome, J.L. Elia, and V.M. Rotello*. Cytosolic Protein Delivery Using Modular Biotin–Streptavidin Assembly of Nanocomposites. American Chemical Society Nano. 18 Apr 2022.
- S. Fedeli/J. Im, S. Gopalakrishnan, J.L. Elia, A. Gupta, D. Kim, and V.M. Rotello*. Nanomaterial-based bioorthogonal catalysts in biological environment. Chemical Society Reviews. 15 Nov 2021.
- Y. Lee, D.C. Luther, R. Goswami, T. Jeon, V. Clark, J. Elia, S. Gopalakrishnan, V.M. Rotello*. Direct Cytosolic Delivery of Proteins through Coengineering of Proteins and Polymeric Delivery Vehicles. Journal of the American Chemical Society. 12 Feb 2020.