Gibney, Brian R.

Academic Appointments:

Professor, Chemistry Department, Brooklyn College, The City University of New York
Faculty, Chemistry and Biochemistry PhD Programs, The Graduate Center, The City University of New York

Degree(s) and awards

E. Ann Nalley Regional Award for Volunteer Service to the American Chemical Society, 2020
Outstanding Chemistry Teacher Award, New York Local Section of the ACS, 2019
American Chemical Society Fellow, 2018
Camille Dreyfus Teacher-Scholar, 2005-2010
Ph.D. (Chemistry) The University of Michigan, 1994

Research Focus:

The Gibney laboratory is focused on developing the nascent field of de novo metalloprotein design as a constructive methodology to delineate the fundamental engineering of metalloproteins, and to utilize their distinct chemistry for therapeutic use.  Currently, we are delineating the role(s) of zinc ions in controlling gene expression in human cancer via the zinc finger proteins (ZFPs).  Our investigative tools center on measuring the thermodynamics of metal-peptide and metal-protein equilibria.  Our near-term goal is to provide the basis for improvements in the computational design of metalloproteins toward his long-term goal of designing synthetic metalloproteins of therapeutic value. Our studies reveal biochemical design principles that have advanced the field to the point where multi-cofactor metalloproteins like those involved in human cancer can be rationally designed and structurally characterized.

Zinc finger proteins are the largest class of metalloproteins in the human genome and their gene regulation function is fundamental to numerous human cancers.  ZFPs exhibit metal-induced protein folding events, where the ZFP is unfolded in the absence of zinc and folds into its biologically active form upon zinc ion binding.  The coupled nature of metal-ion binding and protein folding obscured the thermodynamics of each since their discovery in the 1980’s.  Using a simple designed peptide with the classic ZFP coordination motifs, the Gibney laboratory was able to decouple the thermodynamics and show that the cost of protein folding free energy (+0-5 kcal/mol) is minimal compared to the free energy of Zn(II) binding, -15 kcal/mol.  Current work is focused on the interaction of zinc with human transcription factor IIB and the Wilms Tumor Suppressor.

 

Selected Publications:

  • Aussignargues, C.; Pandelia, M.-E.; Sutter, M.; Plegaria, J.S.; Zarzycki, J.; Turmo, A.; Huang, J.; Ducat, D.C.; Hegg, E.L.; Gibney, B.R.; Kerfeld, C.A. “Structure and Function of a Baterial Microcompartment Shell Protein Engineered to bind a [4Fe-4S] Cluster”, Am. Chem. Soc. 2016, 138, 5262-5270.
  • Reddi, A.R.; Pawlowska, M.; Gibney, B.R.; “Evaluation of the Intrinsic Zn(II) Affinity of a Cys3His1 Site in the Absence of Protein Folding Effects”, Chem., 2015, 54, 5942-5948.
  • Chan, K.L.; Bakman, I.; Marts, A.R.; Batir, Y.; Dowd. T.L.; Tierney, D.L.; Gibney, B.R.; “Characterization of the Zn(II) Binding Properties of the Wilms’ Tumor Suppressor Protein C-terminal Zinc Finger Peptide”, Inorganic Chemistry, 2014, 53, 6309-6320.
  • Reddi, A.R.; Guzman, T.; Breece, R.M.; Tierney, D.L.; Gibney, B.R. ” Deducing the Energetic Cost of Protein Folding in Zinc Finger Proteins Using Designed Metallopeptides”, Am. Chem. Soc., 2007, 129, 12815-12827.
  • Reddi, A.R.; Gibney, B.R. ” The Role of Protons in the Thermodynamic Contribution of a Zn(II)-Cys4Site Toward Protein Stability”, Biochemistry, 2007, 46, 3745-3758.

 

Patents: None

Grants over the last 5 years: No federal grant