Fields of Research
Protein kinases
A-kinase anchoring proteins
Molecular basis of disease
Protein structure
Research Summary
Biochemically characterising the fusion kinase DNAJ-PKAc and its role in the pathogenesis of fibrolamellar carcinoma (FLC).
Research Statement
More than 500 kinases constituting the human kinome regulate key processes in the human body, including cell growth, signal transduction and metabolism. Critically, one third of the kinome is currently uncharacterised. These dark kinases represent a potential untapped font for therapeutic intervention of a variety of diseases, including neurodegenerative disorders, inflammatory conditions, and cancer. Fibrolamellar carcinoma (FLC) is a rare type of adolescent liver cancer uniquely characterised by the presence of a de novo chimeric gene product – the fusion kinase DNAJ-PKAc. However, the precise mechanisms by which DNAJ-PKAc promotes tumorigenesis is poorly understood. Further, FLC tumours are resistant to conventional treatment modalities. My current work is focused on biochemically characterising a library of novel DNAJ-PKAc inhibitors to therapeutically treat FLC and to determine the structure of the DNAJ-PKAc:BAG2:Hsp70 oligomeric complex.
Awards and Honors
Posters: Biochemical Society, 88th Harden Conference: Beyond Catalysis: kinases and pseudokinases, 2022
Luke McAloon
Postdoctoral Scholar
Affiliations
Fibrolamellar Cancer Foundation (FCF)
Luke McAloon
Postdoctoral Scholar
Affiliations
Fibrolamellar Cancer Foundation (FCF)
Contact Information
- Building:
- K Wing
- Room:
- K-322
- Box:
- 357750
Lab
- Building:
- K Wing
- Room:
- K-322
- Box:
- 357750
Luke McAloon
Postdoctoral Scholar
Affiliations
Fibrolamellar Cancer Foundation (FCF)
Luke McAloon
Postdoctoral Scholar
Affiliations
Fibrolamellar Cancer Foundation (FCF)
Luke McAloon
Postdoctoral Scholar
Affiliations
Fibrolamellar Cancer Foundation (FCF)
Select Publications
McAloon LM, Muller AG, Nay K, Lu EL, Smeuninx B, Means AR, Febbraio MA, Scott JW. CaMKK2: bridging the gap between Ca2+ signaling and energy-sensing. Essays Biochem. 2024 Nov 18;68(3):309-320. doi: 10.1042/EBC20240011. PMID: 39268917; PMCID: PMC11576191.
Horne CR, Dite TA, Young SN, Mather LJ, Dagley LF, Johnson JL, Yaron-Barir TM, Huntsman EM, Daly LA, Byrne DP, Cadell AL, Ng BH, Yousef J, Multari DH, Shen L, McAloon LM, Manning G, Febbraio MA, Means AR, Cantley LC, Tanzer MC, Croucher DR, Eyers CE, Eyers PA, Scott JW, Murphy JM. PSKH1 kinase activity is differentially modulated via allosteric binding of Ca2+ sensor proteins. Proc Natl Acad Sci U S A. 2025 Feb 25;122(8):e2420961122. doi: 10.1073/pnas.2420961122. Epub 2025 Feb 18. PMID: 39964718; PMCID: PMC11873932.
Kaiser J, Nay K, Horne CR, McAloon LM, Fuller OK, Muller AG, Whyte DG, Means AR, Walder K, Berk M, Hannan AJ, Murphy JM, Febbraio MA, Gundlach AL, Scott JW. CaMKK2 as an emerging treatment target for bipolar disorder. Mol Psychiatry. 2023 Nov;28(11):4500-4511. doi: 10.1038/s41380-023-02260-3. Epub 2023 Sep 20. PMID: 37730845; PMCID: PMC10914626.
Nay K, Smiles WJ, Kaiser J, McAloon LM, Loh K, Galic S, Oakhill JS, Gundlach AL, Scott JW. Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders. Int J Mol Sci. 2021 Apr 14;22(8):4052. doi: 10.3390/ijms22084052. PMID: 33919972; PMCID: PMC8070923.
Langendorf CG, O’Brien MT, Ngoei KRW, McAloon LM, Dhagat U, Hoque A, Ling NXY, Dite TA, Galic S, Loh K, Parker MW, Oakhill JS, Kemp BE, Scott JW. CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins. J Biol Chem. 2020 Nov 27;295(48):16239-16250. doi: 10.1074/jbc.RA120.013756. Epub 2020 Sep 9. PMID: 32913128; PMCID: PMC7705300.
Publications
Luke McAloon
Postdoctoral Scholar
Affiliations
Fibrolamellar Cancer Foundation (FCF)