Isabelle Kwan’s NIH Fellowship Application

We wholeheartedly congratulate Isabelle Kwan on her outstanding research project proposal for the NIH Ruth L. Kirschstein National Research Service Award for Individual Predoctoral M.D./Ph.D. Fellowships (F30).

Isabelle’s grant proposal, “From Resistance to Innovation: Towards Countering Asciminib Resistance and Designing Next-Generation Allosteric Inhibitors against CML,”  received a 9th-percentile score. The project advances a multidisciplinary approach that integrates in silico modeling and simulations with biochemical in vitro and in cellulo studies, in collaboration with the Markus Seeliger Lab at Stony Brook University and the Neil Shah Lab at UCSF, to elucidate mechanisms of asciminib resistance and to inform the development of next-generation therapeutics targeting the oncodriver BCR::ABL1 kinase.  

Isabelle Kwan is currently an NIH T32 awardee pursuing her PhD studies in Chemistry under the mentorship of Professor Ivet Bahar at the Laufer Center, as part of the MSTP program of the School of Medicine. She is also a fellow of Stony Brook's Chemical Biology Training Program.

Clinically observed ABL1 mutation sites (spheres) in asciminib-treated patients distributed across SH2-kinase domain linker (gray), N-lobe (violet), ATP-binding cleft (teal), C-lobe (lime), and myristoyl-binding pocket (yellow). Residue labels correspond to wild-type amino acids with ABL1a numbering. Nilotinib and asciminib bind at orthosteric and allosteric sites, represented as teal and pink sticks, respectively (PDB: 5mo4). We, together with Seeliger and Shah groups, have previously reported asciminib resistance in ABL1 variant lacking exon 2 (cyan ribbon) (Leyte-Vidal, et al. Leukemia. 2024.).