Brian C. Freeman
Office: (217) 244-2662
Lab: (217) 244-1065
Mail to: Dept. of Cell & Developmental Biology
University of Illinois
601 S. Goodwin Avenue
Urbana, IL 61801
Professor of Cell and Developmental Biology
Alexander von Humboldt Scholar
Chromatin Structure, Genome Organization, Genomics, Protein Homeostasis, Proteomics, Regulation of Gene Expression
Disease Research Interests
Aging Related Diseases, Cancer, Metabolic Disorders/Diabetes
B.S., University of Michigan (Microbiology)
Ph.D., Northwestern University (Biochemistry and Biophysics)
Postdoctorate, University of California-San Francisco
Molecular Chaperones; Transcription; Chromatin Remodeling; Genome Organization
Physiological balance is maintained, in part, through the rapid and well-timed assembly and disassembly of biological complexes. The dynamic interplay between select factors, including but not limited to proteins and nucleic acids, facilitates an efficient and functional cell environment. In general, pathways are driven forward through cooperative interactions thereby providing important features—rapid and robust action with limited energy input. However, within multi-step pathways cooperative stable assemblies have drawbacks since each complex is recalcitrant to dissociation. Hence, transitions between functional complexes or termination of action would be slow unless catalyzed. Despite the commonality of this problem, the possible cellular mechanisms promoting disassembly-events are not well understood. The primary focus of our laboratory is to identify and characterize the machinery driving a dynamic protein environment.
The Freeman research team exploits three central nuclear processes, transcription, chromatin remodeling, and genome reorganization, as molecular paradigms for understanding how the action of any single system can impact homeostasis, as dysfunction of these pathways can lead to cell death or uncontrolled growth (i.e., cancer). Since these processes employ a number of factors with common binding specificities, a decline in pathway efficiency is highly plausible due to the misassembly of individual complexes or an impairment in the disassembly of the utilized structures. The fundamental properties of molecular chaperones (abundant proteins with promiscuous but weak binding activities) allow biological factors to avoid these challenges by cultivating a self-organizing environment that fosters rapid action. In essence, the ability of molecular chaperones to promote protein dynamics parallels the more established chaperone roles in protein folding in which a chaperone does not dictate the final folded structure (path direction) but rather helps the nascent chain (system) avoid off-pathway energy barriers that commonly occur in protein folding (multi-step) energy landscapes. Our end goal is to understand the mechanisms by which molecular chaperones foster a dynamic nuclear environment thereby ensuring cell and organismal homeostasis.
TUM Ambassador, Technische Universität München, 2015.
Friedrich Wilhelm Bessel Research Award, Alexander von Humboldt Foundation, 2010.
Honorary Hans Fischer Senior Fellow, TUM-IAS, 2010.
Educator of the year. Alumni Association, University of Illinois, 2009.
American Heart Association Fellow, 2000-2002.
Leukemia and Lymphoma Society Fellow, 1997-2000.
Leukemia Research Foundation Fellow, 1996-1997.
Wang, A., J.A. Kolhe, N. Gioacchini, I. Baade, W.M. Brieher, C.L. Peterson and B.C. Freeman (2020) Mechanism of Long-Range Chromosome Motion Triggered by Gene Activation. Dev. Cell, 52, 309-320. (ABSTRACT)
Gvozdenov, Z., L. Bendix, J. Kolhe and B.C. Freeman (2019) The Hsp90 Molecular Chaperone Regulates the Transcription Factor Network Controlling Chromatin Accessibility. J. Mol. Biol., 431, 4993-5003. (ABSTRACT)
Gvozdenov, Z., J. Kolhe and B.C. Freeman (2019) The Nuclear and DNA-Associated Molecular Chaperone Network. Cold Spring Harb Perspect Biol, 11, pii:a034009. (ABSTRACT)
Echtenkamp, F.J., Z. Gvozdenov, N.L. Adkins, Y. Zhang, M.A. Day-Lynch, S. Watanabe, C.L. Peterson and B.C. Freeman (2016) Hsp90 and p23 chaperones control chromatin architecture by maintaining the functional pool of the RSC remodeler. Mol. Cell, 64, 888-899. (ABSTRACT)
Zelin, E. and B.C. Freeman (2015) Lysine deacetylases regulate the heat shock response including the age-associated impairment of HSF1. J. Mol. Biol., 427, 1644-1654. (ABSTRACT)
Echtenkamp, F.J. and B.C. Freeman (2014) Molecular Chaperone-Mediated Nuclear Protein Dynamics. Curr. Prot. Pept. Sci., 15, 216-224. (ABSTRACT)
Zelin, E., Y. Zhang, O.A. Toogun, S. Zhong and B.C. Freeman (2012) The p23 Molecular Chaperone and GCN5 Acetylase Jointly Modulate Protein-DNA Dynamics and Open Chromatin Status. Mol. Cell, 48, 459-470. (ABSTRACT)
Echtenkamp, F.J., E. Zelin, E. Oxelmark, J.I. Woo, B.J. Andrews, M.J. Garabedian and B.C. Freeman (2011) Global Functional Map of the p23 Molecular Chaperone Reveals an Extensive Cellular Network. Mol. Cell, 43, 229-241. (ABSTRACT)