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.
- Louw-du Toit, R., Hapgood, J.P. and Africander, D. (2020). A direct comparison of the transcriptional activities of progestins used in contraception and menopausal hormone therapy via the mineralocorticoid receptor. Biochem. Biophys. Res. Commun., doi: 10.1016/j.bbrc.2020.03.100. [Epub ahead of print].
- 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., doi: 10.1089/aid.2019.0228. [Epub ahead of print].
- 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
- Heffron, R., Achilles, S.L., Dorflinger, L.J., Hapgood, J.P., Kiarie, J., Polis, C.B., Steyn, P.S. (2018). 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, 199, 199-204.
- Tomasicchio, M., Davids, M., Pooran, A., Theron, G., Smith, L., Semple, L., Meldau, R., Hapgood, J., Dheda, K. (2018). The injectable contraceptive medroxyprogesterone acetate attenuates Mycobacterium tuberculosis-specific host immunity through the glucocorticoid receptor. J. Infect. Dis., 219,1329-1337.
- Bick A.J., Hapgood J.P. (2018). HIV-1 Latency Is Maintained by the Estrogen Receptor. Trends Microbiol. 26, 891-892
- 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 JP, Kaushic C, Hel Z. (2017). Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms. Endocr Rev. 39, 36-78
- Polis CB, Achilles SL, Hel Z & Hapgood JP. (2017). Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women’s risk of HIV? Contraception. 97, 191-197
- Louw-du Toit, R., Perkins, M. S., Hapgood, J. P., & Africander, D. (2017). Comparing the androgenic and estrogenic properties of progestins used in contraception and hormone therapy. Biochem Biophys Res Commun. 491, 140-146
- Hapgood, J. P., Avenant, C., & Moliki, J. M. (2016). Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy. Pharmacol Ther. 165, 93-113.
A/Prof Donita J. Africander (Dept Biochemistry, Stellenbosch University)
Dr Charles Morrison (FHI 360, North Carolina, USA)
Dr Pai-Lien Chen (FHI 360, North Carolina, USA)
Dr Karl Storbeck (Dept Biochemistry, Stellenbosch University)
Dr Léanie Kleynhans (Department of Biomedical Sciences, Stellenbosch University)
Dr Mandisa Singata-Madliki (Co-director Effective Care Research Unit, University of the Witwatersrand)
Prof Zephne van der Spuy (Dept Obstetrics and Gynaecology, Groote Schuur Hospital)
Dr Michele Tomasicchio (Centre for Lung Infection & Immunity, Division of Pulmonology and UCT Lung Institute, Dept of Medicine, UCT)
Prof Hennie Botha (Dept of Obstetrics and Gynaecology and Unit for Gynaecological Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University)
Prof Justus Hofmeyr (Dept of Obstetrics and Gynaecology, Frere and Cecilia Makiwane Hospitals; Effective Care Research Unit, University of the Witwatersrand)
A/Prof Jenni Smit (MatCH Research Unit, Dept of Obstetrics and Gynaecology, University of the Witwatersrand)
Dr Mags Beksinska (MatCH Research Unit, Dept of Obstetrics and Gynaecology, University of the Witwatersrand)