Department of Molecular and Cell Biology, Faculty of Science, UCT; and Member, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, UCT.
Professor 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 J. (2020). Is the injectable contraceptive Depo-medroxyprogesterone acetate (DMPA-IM) associated with an increased risk for HIV acquisition? The jury is still out. AIDS Res.Hum. Retroviruses. 36(5), 357-366.
Dlamini, S., Kuipa, M., Enfield, K., Skosana, S., Woodland, J.G., Moliki, J.M., Bick, A.J., van der Spuy, Z., Maritz, M.F., Avenant, C. and Hapgood, J.P. (2019). Reciprocal modulation of antiretroviral drug and steroid receptor function in vitro. Antimicrob. Agents Chemother. 64(1), e01890-01819
Skosana, S. B., Woodland, J. G., Cartwright, M., Enfield, K., Komane, M., Louw-du Toit, R., van der Spuy, Z., Avenant, C., Africander, D., Storbeck, K. H. and Hapgood, J. P. (2019). Differential metabolism of clinically-relevant progestogens in cell lines and tissue: Implications for biological mechanisms. J. Steroid Biochem. Mol. Biol. 189,145-153.
Ray, R. M., Maritz, M. F., Avenant, C., Tomasicchio, M., Dlamini, S., van der Spuy, Z.., and Hapgood, J. P. (2019). The contraceptive medroxyprogesterone acetate, unlike norethisterone, directly increases R5 HIV-1 infection in human cervical explant tissue at physiologically relevant concentrations. Sci. Rep. 9, 4334.
Heffrom, R., Achilles, S.L., Dorflinger, L.J., Hapgood, J.P., Kiarie, J., Polis, C.B., Steyn, P.S. (2019). Pharmacokinetic, biologic, and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women. Contraception. 99, 199-204.
Maritz, M. F., Ray, R. M., Bick, A. J., Tomasicchio, M., Woodland, J. G., Govender, Y., Avenant, C., and Hapgood, J. P. (2018). Medroxyprogesterone acetate, unlike norethisterone, increases HIV-1 replication in human peripheral blood mononuclear cells and an indicator cell line, via mechanisms involving the glucocorticoid receptor, increased CD4/CD8 ratios and CCR5 levels. PLoS One. 13, e0196043.
Hapgood J. P., Kaushic, C., and Hel, Z. (2018). Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms. Endocr Rev. 39, 36-78.
Polis C. B., Achilles, S. L., Hel, Z., and Hapgood, J. P. (2018). Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women's risk of HIV? Contraception, 97, 191-197.
Hapgood J. P., Avenant, C., and Moliki, J. M. (2016). Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy. Pharmacol. Ther. 165, 93-113.
Africander D. J., Storbeck, K., and Hapgood. J. P. (2014). A comparative study of the androgenic properties of progesterone and the progestins, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A). J. Steroid Biochem. Mol. Biol. 143, 404-415
Room 428, Level 4
Dept of Molecular and Cell Biology, Faculty of Science, Upper Campus
University of Cape Town