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Gerald M. Wilson

Gerald M. Wilson Ph.D.

Academic Title: Associate Professor
Primary Appointment: Biochemistry and Molecular Biology
Additional Title(s): Director, Graduate Program in Biochemistry and Molecular Biology
Location: 108NG, 239
Phone: 410-706-8904

Personal History:

Dr. Wilson earned his B.Sc. and Ph.D. degrees in Biochemistry from Queen’s University in Kingston, Canada. He then completed post-doctoral training at Wake Forest University and the University of Medicine and Dentistry of New Jersey. In 2002 he joined the faculty of the University of Maryland School of Medicine as an Assistant Professor of Biochemistry and Molecular Biology and was promoted to Associate Professor with tenure in 2009.

Dr. Wilson is also a member of the Molecular and Structural Biology Program within the University of Maryland Marlene and Stewart Greenebaum Cancer Center Program in Oncology, and collaborates with both basic and clinical research investigators to identify and characterize post-transcriptional gene regulatory mechanisms the contribute to oncogenesis and tumor development. His research program has been supported by the National Institutes of Health, the American Cancer Society, and the American Heart Association.

Research Interests:

The Wilson lab studies cellular mechanisms that regulate the production of many important gene products, including oncoproteins, inflammatory mediators, and lipoprotein receptors. In particular, they focus on protein factors that regulate cytoplasmic mRNA turnover rates, and the signaling systems that may transiently modulate the activity of these factors. Experimental approaches vary from cell and molecular biology (cultured cell systems, transfection, RNA interference) to biochemical (gel mobility shift, protein-protein and protein-RNA cross-linking) and biophysical systems (fluorescence anisotropy, resonance energy transfer). Some current foci of interest include:

Trans-acting factors that regulate decay of oncoprotein and inflammatory mediator mRNAs

Many mRNAs encoding oncoproteins and inflammatory mediators contain AU-rich mRNA-destabilizing elements (AREs) in their 3’-untranslated regions. AREs regulate mRNA decay by interacting with cellular ARE-binding factors. For example, tristetraprolin (TTP) or selected AUF1 isoforms induce decay of some ARE-containing mRNAs, while other proteins, like HuR, protect these transcripts from degradation. Recent data also show that microRNAs (miRNAs) and associated proteins can influence ARE-directed mRNA decay. In humans, over 4000 different transcripts contain AREs, yet these sequences share few common features. However, AREs from homologous mRNAs are highly conserved, indicating that the unique sequence composition of each ARE serves one or more essential functions. The Wilson lab’s long-term objective is to determine how the size and sequence diversity of AREs directs post-transcriptional regulation at the gene-specific level.

The role of post-transcriptional gene regulatory circuits in tumor development

In 2009, the Wilson lab discovered that expression of the mRNA-destabilizing protein tristetraprolin (TTP) was significantly repressed in most human cancers, including aggressive tumors of the breast and prostate. Furthermore, analyses of gene array datasets revealed that suppression of TTP is a negative prognostic indicator in breast cancer, since patients with low TTP expression in breast tumors prior to surgical excision were more likely to present: (i) increased pathological tumor grade, (ii) increased expression of the pro-angiogenic factor VEGF, and (iii) increased risk of death from recurrent breast cancer. Subsequently, they showed that restoring TTP expression in a cultured cancer cell line suppressed three key tumorigenic phenotypes: (i) cell proliferation, (ii) resistance to pro-apoptotic stimuli, and (iii) expression of VEGF mRNA. These findings are consistent with a model whereby cancer cells that lower TTP production develop more aggressive characteristics, likely as a result of increased expression of mRNAs that would otherwise be suppressed by TTP. Ongoing studies in the lab on this project are asking: (i) what TTP-targeted mRNAs are responsible for enhancing tumorigenic phenotypes? and (ii) what cellular mechanisms are suppressing TTP expression in aggressive tumors?

mRNA stability as a novel mechanism to enhance hepatic LDL receptor expression

Hepatic low density lipoprotein (LDL) receptors are essential for efflux of cholesterol-rich LDL particles from the circulation and subsequent cholesterol excretion via bile acid formation. High circulating LDL levels are a prime risk factor for the development of atherosclerotic plaques, contributing to myocardial infarction and related mortality. As such, hepatic regulatory systems that control LDL receptor production are promising targets for the development of novel, aggressive therapies to lower plasma LDL concentrations. The Wilson lab has found that activation of the protein kinase C system stabilizes LDL receptor mRNA in cultured liver cell models, leading to enhanced production of LDL receptor protein and cellular LDL binding. This mRNA stabilization event requires the JNK kinase cascade, but does not appear to involve any known mRNA stability determinants. Ongoing work in the lab is focused on identifying specific LDL receptor mRNA sequences required for JNK-dependent stabilization, and trans-acting factors that functionally interact with this element.

Laboratory Personnel:

  • Elizabeth White, Ph.D., lab manager
  • Christina Ross, B.S., graduate student


Yoon, J., De, S., Srikantan, S., Abdelmohsen, K., Grammatikakis, I., Kim, J., Kim, K.M., Noh, J.H., White, E.J.F., Martindale, J.L., Yang, X., Kang, M., Wood 3rd, W.H., Hooten, N.N., Evans, M.K., Becker, K.G., Tripathi, V., Prasanth, K.V., Wilson, G.M., Tuschl, T., Ingolia, N.T., Hafner, M., and Gorospe, M. (2014) PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. Nat. Commun. 5, 5248.

Zucconi, B.E. and Wilson, G.M. (2013) Assembly of functional ribonucleoprotein complexes by AU-rich element RNA-binding protein 1 (AUF1) requires base-dependent and -independent RNA contacts. J. Biol. Chem. 288, 17759-17768.

Kishor, A., Tandukar, B., Ly, Y.V., Toth, E.A., Suarez, Y., Brewer, G., and Wilson, G.M. (2013) Hsp70 is a novel posttranscriptional regulator of gene expression that binds and stabilizes selected mRNAs containing AU-rich elements. Mol. Cell. Biol. 33, 71-84.

White, E.J.F., Brewer, G., and Wilson, G.M. (2013) Post-transcriptional control of gene expression by AUF1: Mechanisms, physiological targets, and regulation. Biochim. Biophys. Acta 1829, 680-688.

Mahat, D.B., Brennan-Laun, S.E., Fialcowitz-White, E.J., Kishor, A., Ross, C.R., Pozharskaya, T., Rawn, J.D., Blackshear, P.J., Hassel, B.A., and Wilson, G.M. (2012) Coordinated expression of tristetraprolin post-transcriptionally attenuates mitogenic induction of the oncogenic Ser/Thr kinase Pim-1. PLoS One 7, e33194.

Ross, C.R., Brennan-Laun, S.E., and Wilson, G.M. (2012) Tristetraprolin: roles in cancer and senescence. Ageing Res. Rev. 11, 473-484.

Zucconi, B.E. and Wilson, G.M. (2011) Modulation of neoplastic gene regulatory pathways by the RNA-binding factor AUF1. Front. Biosci. 16, 2307-2325.

Zucconi, B.E., Ballin, J.D., Brewer, B.Y., Ross, C.R., Huang, J., Toth, E.A., and Wilson, G.M. (2010) Alternatively expressed domains of AU-rich element RNA-binding protein 1 (AUF1) regulate RNA-binding affinity, RNA-induced protein oligomerization, and the local conformation of bound RNA ligands. J. Biol. Chem. 285, 39127-39139.

Brennan, S.E., Kuwano, Y., Alkharouf, N., Blackshear, P.J., Gorospe, M., and Wilson, G.M. (2009) The mRNA-destabilizing protein tristetraprolin is suppressed in many cancers, altering tumorigenic phenotypes and patient prognosis. Cancer Res. 69, 5168-5176.

Vargas, N.V., Brewer, B.Y., Rogers, T.B., and Wilson, G.M. (2009) Protein kinase C activation stabilizes LDL receptor mRNA via the JNK pathway in HepG2 cells. J. Lipid Res. 50, 386-397.

Ballin, J.D., Prevas, J.P., Bharill, S., Gryczynski, I., Gryczynski, Z., and Wilson, G.M. (2008) Local RNA conformational dynamics revealed by 2-aminopurine solvent accessibility. Biochemistry 47, 7043-7052.

Ballin, J.D., Bharill, S., Fialcowitz-White, E.J., Gryczynski, I., Gryczynski, Z., and Wilson, G.M. (2007) Site-specific variations in RNA folding thermodynamics visualized by 2-aminopurine fluorescence. Biochemistry 46, 13948-13960.

Fialcowitz-White, E.J., Brewer, B.Y., Ballin, J.D., Willis, C.D., Toth, E.A., and Wilson, G.M. (2007) Specific protein domains mediate cooperative assembly of HuR oligomers on AU-rich mRNA-destabilizing sequences. J. Biol. Chem. 282, 20948-20959.

Brewer, B.Y., Ballin, J.D., Fialcowitz-White, E.J., Blackshear, P.J., and Wilson, G.M. (2006) Substrate dependence of conformational changes in the RNA-binding domain of tristetraprolin assessed by fluorescence spectroscopy of tryptophan mutants. Biochemistry 45, 13807-13817.

Fialcowitz, E.J., Brewer, B.Y., Keenan, B., and Wilson, G.M. (2005) A hairpin-like structure within an AU-rich mRNA-destabilizing element regulates trans-factor binding selectivity and mRNA decay kinetics. J. Biol. Chem. 280, 22406-22417.

Brewer, B. Y., Malicka, J., Blackshear, P.J., and Wilson, G. M. (2004) RNA sequence elements required for high affinity binding by the zinc finger domain of tristetraprolin: Conformational changes coupled to the bipartite nature of AU-rich mRNA-destabilizing motifs. J. Biol. Chem., 279, 27870-27877.