George M Burslem, PhD
422 Curie Blvd.
Philadelphia, PA 19104
MSci (Chemistry with Industrial Experience)
University of Bristol , 2011.
PhD (An Integrated Approach to the Discovery of Inhibitors of Protein-Protein Interactions)
University of Leeds, 2015.
Description of Research ExpertiseResearch Interests
Our research is focused on the development of novel chemical approaches to modulate lysine post-translational modifications. This includes both synthetic and protein engineering approaches to understand lysine modifications as well as chemical biology approaches to modulate them as a potential therapeutic approach.
Chemical Biology, Lysine, PTMs, Ubiquitin
Post-translational modifications (PTMs) are key modulators of protein function and are crucial for the successful function of a cell. They can act as methods for signal transduction, alter the localization of a protein or signal that a protein is no longer required, as well as many other functions. The most widely studied PTM is phosphorylation of serine, threonine and tyrosine residues but reversible covalent modifications of lysine residues can have equally important functions. For example, acetylation of lysine residues is the second most observed PTM, after phosphorylation.
The Burslem lab is interested in developing chemical tools to understand and modulate lysine post-translational modifications, specifically acetylation and ubiquitination. The laboratory is particularly interested in novel pharmacological approaches to modulate post-translational modifications which regulate gene expression and protein stability with a focus on understanding and treating haematological malignancies. We employ a multidisciplinary approach including synthetic chemistry, biochemistry, biophysics and cell biology to probe biological systems in cancer biology.
Various rotation projects are available - please contact George for details.
Currently seeking rotation students and post docs – contact George for details.
Selected PublicationsGeorge M Burslem, Craig M Crews: Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery. Cell Jan 2020.
Burslem George M, Schultz Anna Reister, Bondeson Daniel P, Eide Christopher A, Savage Stevens Samantha L, Druker Brian J, Crews Craig M: Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-mediated Targeted Protein Degradation. Cancer research Jul 2019.
Burslem George M, Song Jayoung, Chen Xin, Hines John, Crews Craig M: Enhancing Antiproliferative Activity and Selectivity of a FLT-3 Inhibitor by Proteolysis Targeting Chimera Conversion. Journal of the American Chemical Society 140(48): 16428-16432, Dec 2018.
Burslem George M, Smith Blake E, Lai Ashton C, Jaime-Figueroa Saul, McQuaid Daniel C, Bondeson Daniel P, Toure Momar, Dong Hanqing, Qian Yimin, Wang Jing, Crew Andrew P, Hines John, Crews Craig M: The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study. Cell chemical biology 25(1): 67-77.e3, 01 2018.
Bondeson Daniel P, Smith Blake E, Burslem George M, Buhimschi Alexandru D, Hines John, Jaime-Figueroa Saul, Wang Jing, Hamman Brian D, Ishchenko Alexey, Crews Craig M: Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead. Cell chemical biology 25(1): 78-87.e5, 01 2018.
Burslem George M, Ottis Philipp, Jaime-Figueroa Saul, Morgan Alicia, Cromm Philipp M, Toure Momar, Crews Craig M: Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure-Degradation Relationships. ChemMedChem 13(15): 1508-1512, 08 2018.
Hellerschmied Doris, Serebrenik Yevgeniy V, Shao Lin, Burslem George M, Crews Craig M: Protein folding state-dependent sorting at the Golgi apparatus. Molecular biology of the cell 30(17): 2296-2308, Aug 2019.
Burslem George M, Kyle Hannah F, Nelson Adam, Edwards Thomas A, Wilson Andrew J: Hypoxia inducible factor (HIF) as a model for studying inhibition of protein-protein interactions. Chemical science 8(6): 4188-4202, Jun 2017.
Grison Claire M, Burslem George M, Miles Jennifer A, Pilsl Ludwig K A, Yeo David J, Imani Zeynab, Warriner Stuart L, Webb Michael E, Wilson Andrew J: Double quick, double click reversible peptide "stapling". Chemical science 8(7): 5166-5171, Jul 2017.
Burslem George M, Crews Craig M: Small-Molecule Modulation of Protein Homeostasis. Chemical reviews 117(17): 11269-11301, Sep 2017.
Burslem George M, Kyle Hannah F, Breeze Alexander L, Edwards Thomas A, Nelson Adam, Warriner Stuart L, Wilson Andrew J: Small-molecule proteomimetic inhibitors of the HIF-1α-p300 protein-protein interaction. Chembiochem : a European journal of chemical biology 15(8): 1083-7, May 2014.