Professor Richard C Nicholson B.Sc. (Simon Fraser) Ph.D (Toronto) Post-Doctoral Fellow (IGBMC, Strasbourg)
  Academic Appointments:
  Professor, School of Basic Medical Sciences, Second Military Medical University, Shanghai
  Senior Lecturer, School of Medicine & Public Health, University of Newcastle

Contact Details
 
 

Senior Hospital Scientist Head of Molecular Biology Mothers and Babies Research Centre  Hunter Medical Research Institute The University of Newcastle    Postal Address:  John Hunter Hospital,  Locked Bag 1,  Hunter Region Mail Centre,  Newcastle, Australia, 2310

.........61 (0) 249 214371 .......61 (0) 249 214394    Rick.Nicholson@hnehealth.nsw.gov.au

Memberships:

Research Interests:

A major aim of the research in the Molecular Biology Group is to ultimately determine the molecular mechanisms which control the onset of parturition (labour). Indeed, much of our recent focus has been on studying the role of corticotropin releasing hormone (CRH) in pre-term labour.

My research is funded by the grants from National Health & Medical Research Council, the Hunter Children's Research Foundation, the John Hunter Charitable Foundation and the University of Newcastle. We also have funding with the NIH and the March of Dimes through collaborations with researchers based in the USA.

Corticotropin-releasing hormone (CRH), a neuropeptide, is also expressed in the placenta. There is a progressive increase in the production of placental CRH as gestation progresses, with a peak corresponding to labour. Thus, it has been proposed that placental CRH production may be an important component of a clock to time the onset of human labour. The mechanisms controlling the production of CRH during pregnancy are still poorly understood and, therefore, the molecular mechanisms regulating CRH gene expression are of great interest.

Our research on regulation of the CRH gene promoter has recently focused on understanding the mechanisms of regulation by glucocorticoid steroid hormones and cAMP, and include studies in the mouse anterior pituitary tumour cell line AtT20 and in primary cultures of human placental cells. In addition to the identification of a cAMP Regulatory Element (CRE) as the primary site responsible for both cAMP and glucocorticoid induction, these studies have identified three other regulatory elements within the human CRH promoter which seem to be involved in placenta specific transcriptional regulation.

We have also discovered that the CRE is an essential regulatory site for inhibiting CRH gene expression in the placenta by other steroid hormones including estrogen and progesterone. Studies are ongoing to determine the molecular mechanisms and protein interactions through which these hormones and their nuclear receptors regulate the CRH promoter.

We are currently using several approaches including a yeast based protein-DNA hybrid assay system to identify the proteins which bind to these newly identified elements or to the CRE in placental cells, and isolate their genes. A second major focus of our research has come from our cloning from placenta a novel multifunction protein that functions (1) as a DNA binding transcription factor through the CRE, and (2) as an RNA binding splicing factor. Studies to characterise the structure and function of this protein is a current priority in our group.

Another unexpected discovery during these studies was the identification of a short DNA sequence within the human CRH promoter which may be a transcriptional silencer element. Mutation of this sequence results in an increase in the level of gene expression of the CRH gene in human placental cells. The yeast hybrid technologies are being utilised to identify the protein that binds to this silencer element in placental cells, and to isolate the gene which encodes this protein.

Other areas of research interest include the role of dietary or metabolic changes in fats, and in particular fatty acids, and their link with the nuclear receptor superfamilies, such as the PPAR receptors, in placental development, pre-eclampsia and parturition. In addition, we are currently exploring the epigenetic changes that control CRH gene expression.

  Interested in doing a research degree with us? Check-out some of the projects available here.

 

Publications:

Tang X, Zhu X, Liu S, Nicholson RC, Ni X (2008). "Phytoestrogens induce differential estrogen receptor beta-mediated responses in transfected MG-63 cells." Endocrine. Oct 21. [Epub ahead of print].

Uh A, Nicholson RC, Gonzalez GV, Simmons CF, Gombart A, Smith R & Equils O. (2008). "Lipopolysaccharide stimulation of trophoblasts induces corticotropin-releasing hormone expression through MyD88." American Journal of Obstetrics & Gynecology 199, 317.e1-317.e6.

Hou Y, Tang X, Nicholson RC and Ni X. (2008). "Phorbol Ester Stimulates Corticotropin-Releasing Hormone Gene Promoter Activity through a cAMP Regulatory Element in Primary Placental Cells." Reproductive Sciences 15, 33-9.

Smith R, van Helden D, Hirst J, Zakar T, Read M, Chan EC, Palliser H, Grammatopoulos, D, Nicholson RC, Parkington H. (2007). "Pathological Interactions with the Timing of Birth and Uterine Activation." Australian and New Zealand Journal of Obstetrics and Gynaecology 47, 430-437.

Smith R, Nicholson RC (2007) "Corticotrophin-Releasing Hormone And The Timing Of Birth." Frontiers in Bioscience 12, 912-918.

King BR, Nicholson RC (2007) "Advances in understanding Corticotrophin-Releasing Hormone gene expression." Frontiers in Bioscience 12, 581-590.

Shipman KL, Robinson PJ, King BR, Smith R, Nicholson RC. (2006) "Identification of a Family of DNA-Binding Proteins with Homology to RNA Splicing Factors." Biochemistry & Cell Biology, 84: 9-19.

Ni X, Nicholson RC (2006) "Steroid hormone mediated regulation of Corticotrophin-Releasing Hormone gene expression." Frontiers in Bioscience 11, 2909-2917.

Smith R, Mesiano S, Nicholson R, Clifton V, Zakar T, Chan E-C, Bisits A, Giles W (2005) "The Regulation of Human Parturition". in Birth, stress and disease: Placental-brain interactions. Eds Michael Power & Jay Schulkin. Cambridge University Press, Cambridge UK. pp 74-87

Ni X, Hou Y, Yang R, Tang X, Smith R, Nicholson RC (2004). "Progesterone Receptors A and B Differentially Modulate Corticotropin-Releasing Hormone Gene Expression Through a cAMP Regulatory Element". Cellular & Molecular Life Sciences, 61:1114-1122.

Ni, X., Hou, Y., King, B.R., Tang, X., Read, M.A., Smith, R., Nicholson, R.C. (2004) "Estrogen Receptor Mediated Down-regulation of CRH Gene Expression is Dependent on a cAMP Regulatory Element in Human Placental Syncytiotrophoblast Cells." J Clinical Endocrinology & Metabolism, 89:2312-2318.

Nicholson RC, Ni X, Hou Y, Yang R, Tang X, Smith R (2004). "Progesterone Receptors A and B Differentially Modulate Placental Expression of the CRH Gene Through a CRE". Proceedings of the International Congress of Endocrinology, Medimond srl, Bologna, Italy. p 541-546

Nicholson, R.C., King, B.R., Smith, R. (2004). "Complex regulatory interactions control CRH gene expression". Frontiers in Bioscience, 9:32-39.

Nicholson, R.C. (2004). "Peptide Hormones, Regulation and Gene Expression". In: The Encyclopedia of Endocrine Diseases.
Academic Press, San Diego USA, pp566-572.

Smith R, Mesiano S, Nicholson R, Zakar T, Chan E-C, Bisits A, Clifton V, Giles W (2004) "Control of the Length of Gestation-Lessons from Women." Pre-term Birth Study Group. Eds. Bennet and Thornton. Publisher: Royal College Obstetrics Gynecology.

Smith, R., Mesiano, S., Clifton, V., Chan, E-C., Zakar, T., Nicholson, R., Giles, W., Bisits, A. (2003) "The Pathway To Human Birth." In Cuadernos de Medicina Reproductiva, Ed. Carlos Simón, Editorial Médica Panamericana Volume 9, Number 2

Nicholson, R.C. (2003) "Mechanisms by which steroid hormones regulate the CRH gene". Recent Developments in Endocrinology and Metabolism 1:115-127.

King, B.R., Smith, R., Nicholson, RC. (2002). "Novel glucocorticoid and cAMP interactions on the CRH gene promoter". Molecular and Cellular Endocrinology 194:19-28.

Ni, X., Nicholson, R.C., King, B.R., Chan, E-C., Read, M.A., Smith, R. (2002). "Estrogen Represses Whereas the Estrogen-Antagonist ICI 182780 Stimulates Placental Corticotropin-Releasing Hormone Gene Expression". J. Clinical Endocrinology & Metabolism 87: 3774-3778.

Nicholson, R.C., King, B.R. (2001). “Regulation of CRH gene expression in the placenta.” Frontiers of Hormone Research 27: 246-257.

King, B.R., Smith, R., Nicholson, R.C. (2001). “The regulation of human corticotropin-releasing hormone gene expression in the placenta”. Peptides 22:1941-7.

King, B.R., Nicholson, R., Smith, R. (2001).  “Placental Corticotrophin-Releasing Hormone, local effects and fetomaturnal endocrinology”.  Stress, 4: 219-233.

Cheng, Y-H.., Nicholson, R.C., King, B., Chan, E-C., Fitter, J.T., Smith, R. (2000). “Glucocorticoid stimulation of corticotropin-releasing hormone gene expression requires a 3’,5’-cyclic AMP regulatory element in human primary placental cytotrophoblast cells”. J. Clinical Endocrinology & Metabolism 85: 1937-1945.

Cheng, Y-H.., Nicholson, R.C., King, B., Chan, E-C., Fitter, J.T., Smith, R. (2000). “CRH gene expression in primary placental cells is modulated by cAMP”.  J. Clinical Endocrinology & Metabolism 85: 1239-1244.

Smith, R., Chan, E-C., Mesiano, S., Nicholson, R.C., Cheng, Y-H., Bowman, M., Clifton, V., Madsen, G., Fitter, J.T., Giles, W., Bisits, A. (1999). “Regulation of Parturition: The Role of CRH.” (Chapter 24) Hormones and Women’s Health: The Reproductive Years. Gordon and Breach Science Publishers.

Bootcov, M. R., Bauskin, A., Valenzuela, S.M., Moore, A.G., Bansal., M., He, X.Y., Zhang, H.P., Donnellan, M., Mahler, S., Pryor, K., Walsh, B., Nicholson, R.C., Fairlie, W.D., Por, S.B., Robbins, J.M., Breit, S.N. (1997). "MIC-1, a novel macrophage inhibitory cytokine, is the first member of a new family within the TGF-b superfamily cluster." Proceedings of the National Academy of Sciences (USA) 94: 11514-11519.

He, X.Y., Smith, G.J., Enno, A., Nicholson, R.C. (1994). "Short term DEN-induced oval cell responses in three strains of mice". Pathology 26: 154-160.

Polly, P., Nicholson, R.C. (1994). "High levels of c-myc gene expression precede point mutational activation of K-ras in mouse lung cancer." Cancer Letters 76: 87-92.

Polly, P., Nicholson, R.C. (1993). "Sequence of the mouse fibronectin-encoding gene promoter region".
Gene 137: 353-354.

Wasylyk, C., Gutman, A., Nicholson, R., Wasylyk, B. (1991). "The c-Ets oncoprotein activates the stromelysin promoter through the same elements as several non-nuclear oncoproteins". EMBO Journal 10: 1127-1134.

Nicholson, R.C., Mader, S., Nagpal, S., Leid, M., Rochette-Egly, C., Chambon, P. (1990). "Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an API binding site". EMBO Journal 9: 4443-4454.

Nicholson, R.C., Williams, D.B., Moran, L.A. (1990). "An essential member of the HSP70 gene family of Saccharomyces cerevisiae is homologous to immunoglobulin heavy chain binding protein."
Proceedings of the National Academy of Sciences (USA) 86: 1159-1163.

Nicholson, R., Murphy, G., Breathnach, R. (1989). "Human and rat malignant-tumor associated mRNAs encode stromelysin-like metalloproteinases". Biochemistry 28: 5195-5203.

Sanchez-Lopez, R., Nicholson, R., Gesnel, M-C., Matrisian, L., Breathnach, R. (1988). "Structure-function relationships in the collagenase family member, transin." Journal of Biological Chemistry 263: 11893-11899.

Nicholson, R.C., Moran, L.A. (1984). " Expression of a Drosophila heat-shock gene in cells of the yeast Saccharomyces cerevisiae." Bioscience Reports 4: 963-972.

Moran, L.A., Chauvin, M., Kennedy, M.E., Korri, M., Lowe, D.G.,
Nicholson, R.C., Perry, M.D. (1983). "The major heat-shock protein (hsp70) gene family: related sequences in mouse, Drosophila, and yeast." Biochemistry and Cell Biology 61: 488-499.

Smith, M.J., Nicholson, R., Stuerzl, M., Lui, A. (1982). "Single copy DNA homology in sea stars".
Journal of Molecular Evolution 18: 92-101.
 

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