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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. Hapgood JP, Kaushic C, Hel Z. (2017). Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms. Endocr Rev. Accepted
  2. Chelsea B. Polis, Sharon L. Achilles, Zdenek Hel & Janet P. Hapgood. (2017). Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women’s risk of HIV? Contraception. Accepted
  3. 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
  4. Hapgood, J. P., Avenant, C., & Moliki, J. M. (2016). Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy. Pharmacol Ther. 165, 93-113
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. Hapgood, J. P. (2013) Immunosuppressive biological mechanisms support reassessment of use of the injectable contraceptive medroxyprogesterone acetate. Endocrinology. 154, 985-988
  16. 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
  17. 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

Dr Donita Africander (Dept Biochemistry, University of Stellenbosch)
Dr Karl Storbeck (Dept Biochemistry, University of Stellenbosch)
Prof Zephne van der Spuy (Department of Obstetrics and Gynaecology, University of Cape Town, Groote Schuur Hospital)
Dr Zdenek Hel (University Alabama at Birmingham, USA)

Lab members

Dr Chanel Avenant  - Research Officer | Involved in all aspects of Prof Hapgood's research, with a specific focus on investigating how different progestins and hormones, acting via Steroid Receptors, influence systemic immunity and HIV-1 pathogenesis.

Sigcinile Dlamini - Scientific Officer (MSc) | Investigating the molecular mechanisms involved in the interactions of hormonal contraceptives and anti-retroviral drugs in the female genital tract and how these influence HIV and other immune functions.

Dr John Woodland - Postdoctoral fellow |  Are hormonal contraceptives, which act via intracellular steroid receptors, implicated in HIV acquisition and, if so, how? As a chemist, I hope to bring a small-molecule approach to this question. Areas of expertise include tissue culture in BSLII and BSLII+ facilities, metabolite profiling via LC-MS and in silico molecular docking.

Calvin Kemp - PhD | EGF-mediated activation of the unliganded glucocorticoid receptor: characterization of cellular mechanisms and physiological role in immune function and anti-inflammatory actions.

Alexis Bick - PhD | Cross talk between the glucocorticoid receptor and the progesterone receptor in modulation of progestin responses and HIV-1 infection.

Mosoko Johnson - PhD | The Role of Pro-Inflammatory Cytokines and Peptide Hormones in Modulation of HIV Pathogenesis in the Female Genital Tract

Kim Enfield - PhD | The progesterone receptors (PR) are involved in regulating mammary gland development, uterine function as well as the maintenance of pregnancy while, the glucocorticoid receptor (GR) plays a pivotal role in regulating immune function. This project aims to investigate the regulation of PR activity by antiretroviral drugs, progestins and the GR. 

Maleshigo Komane - PhD | Investigating biocharacter and mechanisms of progestins used in contraception via the glucocorticoid receptor: Implications for choice of contraceptive and HIV infection. 

Salndave Skosana - PhD | Progestin concentrations, metabolism and ARV interactions: implications for choice of combination therapies in cells and tissues of the female reproductive tract.  

Tawanda Nhundu - MSc | Mechanisms of Glucocorticoid Pro-Inflammatory Effects: Crosstalk and Synergy.   

Michael Kuipa - MSc | Cross talk between anti HIV-1 retroviral drugs, contraceptives and the glucocorticoid receptor.

Karen van der Merwe - Research Administrative Assistant | My duties include helping with fund and lab management, research and general administration, and providing research specific support. 

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