Danton Ivanochko

PHD candidate

Epigenetic signalling directs our development from a single fertilized cell to an adult made from tens of trillions of cells. Cancers frequently hijack specific epigenetic machinery to drive unrestrained growth. As researchers discover how cancers exploit epigenetic mechanisms, we are finding new ways to battle cancer with targeted therapeutics.

My research focuses on a group of epigenetic proteins known as the PRDMs. I used methods from structural biology to understand how PRDMs regulate histone methylation and gene expression. My PhD project covers the following areas:

  • • Structurally describing the first chemical probe for PRDM9.
  • • Characterizing the protein-protein interactions of the NuRD complex with PRDM3 and PRDM16.
  • • Assessing enzyme cofactor binding in the PRDM family.















Publications

 Ivanochko D, Halabelian L, Henderson E, Savitsky P, Jain H, Marcon E, Duan S, Hutchinson A, Seitova A, Barsyte-Lovejoy D, Filippakopoulos P, Greenblatt, Lima-Fernandes, Arrowsmith CH. (2019) Direct interaction between the PRDM3 and PRDM16 tumor suppressors and the NuRD chromatin remodeling complex. Nucleic Acids Res 47: 1225-1238.

Allali-Hassani A, Szewczyk MM, Ivanochko D, Organ SL, Bok J, Ho JSY, Gay FPH, Li F, Blazer L, Eram MS, Halabelian L, Dilworth D, Luciani GM, Lima-Fernandes E, Wu Q, Loppnau P, Palmer N, Talib SZA, Brown PJ, Schapira M, Kaldis P, O'Hagan RC, Guccione E, Barsyte-Lovejoy D, Arrowsmith CH, Sanders JM, Kattar SD, Bennett DJ, Nicholson B, Vedadi M. (2019) Discovery of a chemical probe for PRDM9. Nat Commun 10: 5759.

Houliston RS, Lemak A, Iqbal A, Ivanochko D, Duan S, Kaustov L, Ong MS, Fan L, Senisterra G, Brown PJ, Wang YX, Arrowsmith CH. (2017) Conformational dynamics of the TTD-PHD histone reader module of the UHRF1 epigenetic regulator reveals multiple histone-binding states, allosteric regulation, and druggability. J Biol Chem 292: 20947-20959.



Protein Structures
6MN4
SAM-bound PRDM9 in complex
with MRK-740 inhibitor		 6BW3
RBBP4 in complex with PRDM3 N-terminal peptide
6BW4
RBBP4 in complex with PRDM16 N-terminal peptide 		6WNX
FBXW11-SKP1 in complex with a pSer33/pSer37
Beta-Catenin peptide