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Janet Hapgood | Head of Department

Research | Publications | Collaborations | Lab members | News


Professor Janet Hapgood
janet.hapgood@uct.ac.za | Telephone +27 21 650 3270 | 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, 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. 

Selected publications
  1. 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 
  2. 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
  3. 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. 2018 Dec 18. doi:10.1016/j.contraception.2018.12.001. [Epub ahead of print]
  4. 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]
  5. Bick A.J., Hapgood J.P. (2018). HIV-1 Latency Is Maintained by the Estrogen Receptor. Trends Microbiol. 26, 891-892
  6. 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
  7. Hapgood JP, Kaushic C, Hel Z. (2017). Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms. Endocr Rev. 39, 36-78
  8. 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 
  9. 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
  10. Hapgood, J. P., Avenant, C., & Moliki, J. M. (2016). Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy. Pharmacol Ther. 165, 93-113
  11. Africander, D. J., Storbeck, K., and Hapgood. J. P. (2014). A comparative study of the androgenic properties of progesterone and the synthetic progestins, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A). J Steroid Biochem Mol Biol. 143, 404-415
  12. Louw-du Toit, R., Hapgood, J. P., and Africander, D. (2014). Medroxyprogesterone acetate differentially regulates IL-12 and IL-10 gene expression in a human ectocervical epithelial cell line in a GR-dependent manner. J Biol Chem. 289, 31136-31149
  13. Verhoog, N., Allie-Reid, F., Vanden Berghe, W., Smith, C., Haegeman, G., Hapgood, J., and Louw, A. (2014). Inhibition of Corticosteroid binding globulin (CBG) gene expression by glucocorticoids involves C/EBP. PLoS One. 9, e110702
  14. Govender, Y., C. Avenant, N. J. Verhoog, R. M. Ray, N. J. Grantham, D. Africander and J. P. Hapgood (2014). The injectable-only contraceptive medroxyprogesterone acetate, unlike norethisterone acetate and progesterone, regulates inflammatory genes in endocervical cells via the glucocorticoid receptor. PLoS One. 9(5): e96497
  15. Wehmeyer, L., Du Toit, A., Lang, D.M. and Hapgood, J.P. (2014). 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. J Biol Chem. 289, 10235-10251
  16. Hapgood, J. P., Ray, R. M., Govender, Y., Avenant, C., and Tomasicchio, M. (2014). Differential glucocorticoid receptor-mediated effects on immunomodulatory gene expression by progestin contraceptives: implications for HIV-1 pathogenesis. Am J Reprod Immunol. 71, 505-512
  17. Hapgood, J. P., Africander, D., Louw, R., Ray, R. M., & Rohwer, J. M. (2014). Potency of progestogens used in hormonal therapy: toward understanding differential actions. J Steroid Biochem Mol Biol. 142, 39-47
  18. Robertson, S., Rohwer, J., Hapgood, J. P., and Louw, A. (2013). Impact of Glucocorticoid Receptor Density on Cooperative Ligand-binding, Ligand-independent Dimerization and Basal Priming of Transactivation: A cell culture model. PLoS One. e64831
  19. Tomasicchio, M., Avenant, C., Du Toit, A., Ray, R. M., and Hapgood, J.P. (2013). The progestin-only contraceptive medroxyprogesterone acetate, but not norethisterone acetate, enhances HIV-1 Vpr-mediated apoptosis in human CD4+ T cells through the glucocorticoid receptor. PLoS One. 8, e62895
  20. Africander, D., Louw, R., and Hapgood, J. P. (2013). Investigating the anti-mineralocorticoid properties of synthetic progestins used in hormone replacement therapy.  Biochem. Biophys Res Commun. 433, 305-310 
  21. Hapgood, J. P. (2013) Immunosuppressive biological mechanisms support reassessment of use of the injectable contraceptive medroxyprogesterone acetate. Endocrinology. 154, 985-988 
  22. Robertson, S., Hapgood, J. P., and Louw, A. (2013). Glucocorticoid receptor concentration and the ability to dimerize influence nuclear translocation and distribution. Steroids. 78, 182-194 
  23. Stanczyk, F. Z., Hapgood, J. P., Winer, S., Mishell, D. R. Jr. (2013). Progestogens Used in Postmenopausal Hormone Therapy: Differences in Their Pharmacological Properties, Intracellular Actions, and Clinical Effects. Endocr Rev. 34, 171-208
Collaborations

A/Prof Donita J. Africander (Dept Biochemistry, University of Stellenbosch) 
Dr Karl Storbeck (Dept Biochemistry, University of Stellenbosch)
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, University of Stellenbosch)
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)

Lab members

Dr Chanel Avenant - Research Officer
Dr Alexis Bick - Postdoctoral Fellow
Dr Johnson Mosoko Moliki - Postdoctoral Fellow
Sigcinile Dlamini - Junior Research Fellow (MSc)
Calvin Kemp - PhD
Maleshigo Komane - PhD
Kim Enfield - PhD
Salndave Skosana - PhD
Michael Kuipa - MSc
Karen van der Merwe - Research Administrative Assistant

Also see Prof. Hapgood's IDM site
News: archived article