HOD Department of Molecular and Cell Biology, Faculty of Science, UCT; and Member, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, UCT.
Prof Hapgood's field is broadly in intracellular molecular mechanisms of action of steroid receptors, in particular the glucocorticoid receptor (GR). Research is focussed on ligand-selectivity, regulation of gene expression as well as cross talk between steroid receptors and other signalling pathways, which allows functional integration between stress, reproduction and immune function. This research is conducted in the broad context of reproduction, inflammation, contraception and infectious disease, in particular HIV-1. Different progestins are used in contraception. MPA, widely used as an injectable contraceptive in Sub-Saharan Africa, has been reported in observational clinical studies to increase HIV-1 acquisition, unlike another injectable contraceptive NET-EN. The Hapgood lab is investigating the molecular basis for this difference. Broadly, the lab is investigating the mechanisms and effects on immune function and HIV-1 pathogenesis of different progestin contraceptives via the GR, as well as cross talk between the GR and other receptors, and the role of the unliganded GR. The effects of different progestins via different steroid receptors, as well as their metabolism, is also being investigated. Reciprocal modulation of progestins and ARVs is another area of interest, with a view to choice of combination therapies to inhibit both HIV-1 acquisition and pregnancy. The work on HIV and contraceptives is highly relevant to women’s choice of contraception in areas of high risk of HIV-1 infection in Sub-Saharan Africa and South Africa in particular.
KEY EXPERTISE: Intracellular molecular mechanisms of action of steroid receptors; the glucocorticoid receptor, in the broad context of reproduction, inflammation, contraception and infectious disease, in particular HIV-1.
Hapgood JP, Avenant C, Moliki JM. Glucocorticoid-independent modulation of GR activity: implications for immunotherapy. Pharmacology and Therapeutics (2016)165:93-113.
Nicolette J. D. Verhoog, Andrea Kotitschke, Chanel Avenant and Janet P. Hapgood. Glucocorticoid-independent repression of TNFα-stimulated IL-6 expression by the glucocorticoid receptor: a potential mechanism for protection against an excessive inflammatory response. Journal of Biological Chemistry (2011) 286:19297-19310
Stanczyk FZ, Hapgood JP, Winer S, Mishell DR Jr. Progestogens Used in Postmenopausal Hormone Therapy: Differences in Their Pharmacological Properties, Intracellular Actions, and Clinical Effects. Endocrine Reviews (2013) 34(2):171-208
Wehmeyer, L., Du Toit, A., Lang, D.M. and Hapgood, J.P. Lipid raft- and protein-kinase C-mediated synergism between the glucocorticoid and GnRH receptor signalling pathways results in repression of proliferation via SGK-1 upregulation. Journal of Biological Chemistry (2014) 289(14):10235-51
Room 208, Level 2
Dept of Molecular and Cell Biology, Faculty of Science, Upper Campus
University of Cape Town