Mentor: Catherine A. Musselman, PhD

Year Entered Into Program: 2014

Terminal Degree(s) Received and year: PhD 2020

Affiliations: 

Biochemistry

Research Description

The synthesis of compounds aimed at Boron Neutron Capture Therapy for cancer (BNCT) during undergraduate education. Nuclear Magnetic Resonance was used for characterization purposes.

The SWI/SNF complex contains at its ATPase subunit (BRG1) a bromodomain that is thought to aid in the targeting of SWI/SNF to chromatin. Despite the known ability of bromodomains (BD) to bind acetylated lysines, the measured affinities for acetylated histone tails in vitro are weak. We recently discovered a DNA binding ability of this BD, a property that was uncharacterized until now. We are currently exploring the binding of the BRG1 BD along with an adjacent AT-hook (ATBD construct) for DNA in the context of linear DNA and nucleosomal DNA. We aim at understanding the mechanisms by which the ATBD contribute in the targeting of SWI/SNF for chromatin.

Awards

• Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2015-2017

Publications

1. Sanchez, J.C., Zhang, L., Evoli, S., Schnicker, N.J., Nunez-Hernandez, M., Yu, L., Wereszczynski, J., Pufall, M.A., Musselman, C.A.: The molecular basis of selective DNA binding by the BRG1 AT-hook and bromodomain. Biochim Biophys Acta Gene Regul Mech 1863(8):194566, 2020. PMCID: PMC7350285
2. Morrison, E.A., Sanchez, J.C., Ronan, J.L., Farrell, D.P., Varzavand, K., Johnson, J.K., Gu, B.X., Crabtree, G.R., Musselman, C.A.:  DNA binding drives the association of BRG1/hBRM bromodomains with nucleosomes. Nat Commun 8:16080, 2017.  PMCID: PMC5519978