Janet Hapgood | Molecular and Cell Biology

Publications | Collaborations | Lab members | News

janet.hapgood@uct.ac.za | Telephone +27 21 650 5976 | Facsimile +27 21 650 1861

Research

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, are 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.

Selected publications

Komane, M., Avenant, C., Louw-du Toit, R., Africander, D.J. and Hapgood, J.P. (2022). Differential off-target glucocorticoid activity of progestins used in endocrine therapy. Steroids. 182, 108998. doi: 10.1016/j.steroids.2022.108998
Bick, A. J., Louw-du Toit, R., Skosana, S. B., Africander, D. and Hapgood, J. P. (2021). Pharmacokinetics, metabolism and serum concentrations of progestins used in contraception. Pharmacol. Ther. 222, 107789
Enfield, K., Dlamini, S., Avenant, C., Kuipa, M., and Hapgood, J.P. (2020). Maraviroc, tenofovir disoproxil fumarate and dapivirine, activate progesterone receptor B in the absence of progestogens. Biochem. Biophys. Res. Commun. 533, 1027-1033
Enfield, K., Cartwright, M., Louw-du Toit, R., Avenant, C., Africander, D. and Hapgood, J.P. (2020). Characterisation of progestins used in hormonal contraception and progesterone via the progesterone receptor. Biochem. Biophys. Res. Commun. 533, 879-885
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. 526(2), 466-471
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
Hapgood, J.P. (2020). ECHO: context and limitations. The Lancet 395(10222), e22
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. (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
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. 2018 Nov 19. doi: 10.1093/infdis/jiy657. [Epub ahead of print]
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, 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

Collaborations

A/Prof Donita J. Africander (Dept of Biochemistry, Stellenbosch University)
Dr Charles Morrison (FHI 360, North Carolina, USA)
Dr Pai-Lien Chen (FHI 360, North Carolina, USA)
Dr Karl Storbeck (Dept of Biochemistry, Stellenbosch University)
Dr Léanie Kleynhans (Dept 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 of 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 Justus Hofmeyr (Dept of Obstetrics and Gynaecology, Frere and Cecilia Makiwane Hospitals; Effective Care Research Unit, University of the Witwatersrand; Dept of Obstetrics and Gynaecology, University of Botswana)
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)

Lab members