Arvin Dar, PhD
- ASSISTANT PROFESSOR | Oncological Sciences
- ASSISTANT PROFESSOR | Pharmacological Sciences
Research Topics:Cancer, Drug Design and Discovery, Enzymology, Genetics, Protein Complexes, Structural Biology
Multi-Disciplinary Training AreasBiophysics and Systems Pharmacology [BSP], Cancer Biology [CAB], Immunology [IMM]
BSc, University of Western Ontario
PhD, University of Toronto
Postdoctoral Training, University of California, San Francisco
Damon Runyon-Rachleff Innovation Award
Pew-Stewart Scholar for Cancer Research
NIH Director’s New Innovator Award
Dean's Postdoctoral Prize
Tisch Cancer Institute Developmental Fund Award
BCRP Multidisciplinary Postdoctoral Award
Canadian Graduate Scholarship
Pershing Square Sohn Prize for Young Investigators (PSSCRA)
Through the development and understanding of small molecules, our lab explores links between the regulation of drug targets and the system level properties of biological networks within cells and animals. Our goals are to create new tools to modulate and explore biomolecular function, with a long-term objective of developing innovative medicines for disease. Our work is highly interdisciplinary, employing methods from synthetic organic chemistry, X-ray crystallography, mass spectrometry, informatics, biochemistry and model organism genetics.
In one research area we are investigating one of the most frequently activated pathways in cancer biology: the Ras-Mitogen Activated Protein Kinase (MAPK) pathway. Oncogenic forms of Ras occur in over 20% of all cancers. These mutants have stifled direct pharmacological approaches and inhibitors for the direct effectors of Ras have shown limited or no efficacy in patients. We are exploring new targets or strategies to modulate the Ras pathway through the development of chemical tools. In particular, we are using target-based and systems pharmacology approaches to generate new classes of small molecule modulators for the Ras pathway.
Postdoctoral Fellows: Alex Scopton, Zaigham Khan, Jayasudhan Yerabolu
Current Students: Jia (Annie) Yu, Ryan Smith, Alexander Real, Arthur Chow
Research Assistant: Lisa Silber
Sonoshita M, Scopton AP, Ung PM, Murray MA, Silber L, Maldonado AY, Real A, Schlessinger A, Cagan RL, Dar AC. A whole-animal platform to advance a clinical kinase inhibitor into new disease space. Nature chemical biology 2018 Mar; 14(3).
Dhawan NS, Scopton AP, Dar AC. Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling. Nature 2016 09; 537(7618).
Dar AC, Das TK, Shokat KM, Cagan RL. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature 2012 Jun; 486(7401).
Dar AC, Shokat KM. The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling. Annual review of biochemistry 2011 Jun; 80.
Brennan DF, Dar AC, Hertz NT, Chao WC, Burlingame AL, Shokat KM, Barford D. A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK. Nature 2011 Apr; 472(7343).
Dar AC, Lopez MS, Shokat KM. Small molecule recognition of c-Src via the Imatinib-binding conformation. Chemistry & biology 2008 Oct; 15(10).
Dar AC, Dever TE, Sicheri F. Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR. Cell 2005 Sep; 122(6).