Ian Outhwaite
Education:
B.A. Williams College (2017)
6th Year MSTP
4th Year Graduate Student
Advisor:
Markus Seeliger
Biochemistry & Structural Biology
I study how to selectively inhibit human kinase proteins and reduce off-target effects. I am also interested in how to circumvent on-target resistance to kinase inhibitors. The subject of my thesis work is defining which kinase inhibitors should be used to target specific MET kinase resistance mutations in the treatment of NSCLC and other human cancers. I am evaluating the mechanism of these resistance mutations and utilizing computational, structural, and biophysical approaches to define which inhibitors, or sets of inhibitors, should be used in these clinically relevant populations.
Additional Research Support:
2024 NIH-NCI NRSA F30 Research Fellowship (NIH 1F30CA281272-01A1)
2022 Chemical Biology Research Fellowship (NIH T32-GM136572)
Publications:
* co-equal contribution
# co-corresponding author
(2024) Leyte-Vidal A, DeFilippis R, Outhwaite IR, Kwan I, Lee JY, Leavitt C, Miller KB, Rea D, Rangwala AM, Lou K, Patel S, Alvarez A, Shokat KM, Bahar I, Seeliger MA, Shah NP. Absence of ABL1 exon 2-encoded SH3 residues in BCR::ABL1 destabilizes the autoinhibited kinase conformation and confers resistance to asciminib. Accepted at Leukemia, in publication.
(2024) Jennings RB*, Outhwaite IR*, Granek IA, Haq F. The effects of the physical and professional workplace environments on the well-being of nursing staff. Accepted at AJN, in publication.
(2024) Radin, DP, Shifman, S, Outhwaite, IR, Sharma, A, Bases, R, Seeliger, MA, Tsirka, SE. Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo. JPET. https://doi.org/10.1124/jpet.123.002021
(2023) Outhwaite IR, Singh S, Berger B.-T., Knapp S, Chodera JD, Seeliger MA. Death by a thousand cuts through kinase inhibitor combinations that maximize selectivity and enable rational multitargeting. eLife. doi: https://doi.org/10.7554/eLife.86189
(2023) Outhwaite IR, Seeliger MA. Kinase Activity: Probing conformational dynamics to understand kinase inhibition. eLife. doi: https://doi.org/10.7554/eLife.92753 [Insight article]
(2023) Mingione VR*, Paung Y*, Outhwaite IR*#, Seeliger MA. Allosteric regulation and inhibition of protein kinases. Biochem Soc Trans. 27 February 2023; 51 (1): 373–385. doi: https://doi.org/10.1042/BST20220940
(2022) Peterson AA, Rangwala AM, Thakur MK, Ward PS, Hung C, Outhwaite IR et al. Discovery and molecular basis of subtype-selective cyclophilin inhibitors. Nat Chem Biol. https://doi.org/10.1038/s41589-022-01116-1
(2022) Phillips HE, Jennings RB, Outhwaite IR et al. Motivation to Impact: Medical Student Volunteerism in the COVID 19 Pandemic. Med Sci Educ. doi: https://doi.org/10.1007/s40670-022-01639-1
(2020) Hou X*, Outhwaite IR*, Pedi L, Long SB. Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation. eLife. doi: https://doi.org/10.7554/eLife.62772
Selected Conference Posters / Presentations:
(2023) Death by a Thousand Cuts – Combining Kinase Inhibitors for Selective Target Inhibition and Rational Multitargeting. FASEB The Protein Phosphorylation Conference. Steamboat Springs, Colorado.
(2023) Death by a Thousand Cuts – Combining Kinase Inhibitors for Selective Target Inhibition and Rational Multitargeting. Frontiers at the Chemistry-Biology Interface Symposium. University of Maryland School of Pharmacy, Baltimore, Maryland.
(2022) Maximizing Selective Inhibition of Clinically Observed MET Mutants. Stony Brook University Institute of Chemical Biology and Drug Discovery 16th Annual Symposium. Stony Brook, New York.
(2021) Medical Student Volunteerism During the COVID-19 Pandemic. AAMC Virtual Group on Educational Affairs Joint Regional Conference. Virtual Meeting.
