Research
Our earlier efforts focused on RNA- and DNA-mediated macromolecular recognition that impacted on siRNA- and piRNA-mediated RNA silencing, histone- and DNA-mediated epigenetic regulation, and the role of cGAMP in mediating the cGAS-STING pathway.
The recent focus has been on multi-subunit type III CRISPR systems that generate cyclic oligoadenylate second messengers that target CARF-effector complexes to provide bacterial defense through activation of nucleases, membrane depolarization and metabolite depletion (with Luciano Marraffini lab, Rockefeller). In parallel, efforts are underway to decipher the distinct mechanistic pathways Lamassu, Kiwa and Azaca bacterial systems utilize to defend themselves from phage invasion.
The efforts on SMC and SMC-like systems have focused on protein-DNA complexes mediating Smc5/6 (with Xiaolan Zhao lab, MSKCC). Mre11-Rad50 (with John Petrini lab, MSKCC) and Spo11 (with Scott Keeney, MSKCC) pathways to decipher mechanistic insights into these systems involved in the DNA damage recognition and response (Smc5/6 and Mre11-Rad50) and meiotic recombination (Spo11).
The Patel group is also addressing structure-function challenges in multi-subunit protein-nucleic acid complexes in the leukemia and lymphoma field by focusing on histone lysine methyltransferases of the MLL (with Robert Roeder, Rockefeller) and NSD (with Jonathan Licht, Florida) families, on SMC Cohesin (with Ari Melnick, Weill-Cornell) and on TRIM28 (with Yadira Soto-Feliciano, MIT), which when mutated cause hematological malignancies.
Ongoing efforts are also addressing the application of in silico computational approaches to identify and optimize small molecules that target RNA-dependent RNA polymerase (with Jingyue Ju, Columbia) and 7mGpppAOme capping machineries of corona (SARS-CoV-2), flavi (Dengue DENV) and alpha (Chikungubya CHIKV) viruses.
Current Projects:
- Structure-function studies of
- CRISPR-associated CARF-effector cassettes
- Bacterial antiphage defense
- Structural Maintenance of Chromosomes complexes
- Complexes impacting on leukemias and lymphomas
- Small molecule targeting of pathogenic viruses
Bio
Dinshaw was born in the Zorastrian community in Mumbai, India. He arrived in the US for graduate studies in Chemistry, receiving his PhD in photochemistry from New York University. He then undertook postdoctoral training in biochemistry and biophysics prior to spending 17 years at AT&T Bell Laboratories. He then joined the faculty of Columbia University-Health Sciences as Professor of Biochemistry and Biophysics and after 8 years moved to the Memorial Sloan-Kettering Cancer Center to set up a program in Structural Biology. His research is focused on macromolecular recognition of biological systems initially using NMR approaches and moving on to x-ray crystallography and cryo-EM microscopy approaches.
Distinctions:
- Member, National Academy of Sciences
- Member, American Academy of Arts and Sciences
- AT&T Bell Laboratories Distinguished Technical Staff Award
- Distinguished Alumnus Award, New York University
- Abby Rockefeller Chair in Experimental Therapeutics (MSKCC)
- FEZANA Jamshed and Shirin Guzdar Excellence in Profession Award
- Tan Jiazhen Life Sciences Collaboration Award
- Shitzhang Bei International Award
- Lifetime Achievement Award, American Association of Indian Scientists in Cancer Research