Research at the Stephen Hough Basic Research Laboratory
The Department of Medicine at the Faculty of Medicine and Health Sciences, Stellenbosch University has extensive labs for conducting research using techniques in biochemistry, molecular and cellular biology. These labs are named after Prof Stephen Hough, who was previously director of the labs and head of the Department of Medicine. Currently basic research in the labs is integrated into the clinical Division of Endocrinology and concentrates on the role of stem cells in the pathology associated with obesity, osteoporosis and diabetes.
Although linked to the Division of Endocrinology, the Stephen Hough Basic Science Lab also participates in research emanating from any of the thirteen divisions within the Department of Medicine. This may entail the use of facilities, advice on basic science, to hosting students for post-graduate degrees in research. Techniques regularly used within the labs include cell culture, cellular differentiation, proliferation assays, the measurement of gene and protein expression, flow cytometry, gene array studies, cytokine measurement, apoptosis assays, immunocytochemistry and cell signalling.
Research in the Stephen Hough labs is focused on the normal function and disease-associated pathological dysfunction of mesenchymal stem cells (MSCs), in particular concentrating on the differences between MSC derived from different tissues or depots.
Obesity and its associated comorbidity type 2 diabetes, are associated with MSC dysfunction. Reduced MSC proliferation and/or differentiation within adipose depots may lead to a reduced pool of mature adipocytes which become hypertrophic when excess energy must be stored. These cells may then become insulin resistant and secrete inflammatory cytokines that systemically and locally propagate insulin resistance and ultimately lead to diabetes. As visceral adiposity has been found to be associated with a greater burden of disease compared to subcutaneous adiposity at any specific BMI above 30, we examine and compare the proliferation and differentiation of MSCs from both visceral- and subcutaneous adipose depots. We are interested in elucidating how therapies for diabetes and HIV, such as TZD and specific ARV treatments, differentially affect MSCs in these visceral and subcutaneous adipose depots and consequently change adipose tissue expansion and insulin resistance. Furthermore, under obesogenic conditions, adipose-resident MSCs and hypertrophic adipocytes may recruit and activate inflammatory macrophages, which can accentuate insulin resistance both locally and systemically. Normally macrophages aid wound healing, but in diabetes pro-inflammatory macrophages recruited to adipose tissue have altered functionality and an impaired capacity for wound healing. As dysfunctional macrophages secrete inflammatory cytokines, which are known to modulate the MSC function, there is a tight relationship between macrophage and MSC functionality, which we are investigating.
We have previously investigated how glucocorticoids (GCs) decrease bone MSC proliferation and differentiation, which decreases the number of mature osteoblasts in bone and consequentially skews normal bone turnover to become catabolic. This can result in osteopenia and osteoporosis. We have found that the insulin-mimetic vanadate can inhibit secondary osteoporosis caused by GCs in rats. Currently we are conducting in vitro studies examining how GCs affect the cellular fate and function of primary MSCs derived from cortical bone, marrow and the proximal end of the femur and how vanadate can modulate these effects. We are also investigating how ARVs and TZDs skew MSC differentiation away from an osteoblastogenesis towards adipogenesis, resulting in pathological lipid accumulation within bone, low bone density and increased rate of fragility fractures.
Prof William Ferris: Director of the Stephen Hough Laboratory
Dr Hanel Sadie-Van Gijsen: Senior Lecturer
Dr Mari van de Vyver: Research Scientist
Dr Ellen Andrag: Post-doctoral research Fellow
Mr Alex Jacobs: PhD Student
Ms Cara-Lesley Bartlett: PhD student
Ms Ascentia Seboko: MSc student
Prof Nigel Crowther, Department of Chemical Pathology, NHLS, University of Witwatersrand Medical School, 7 York Rd., Parktown, Johannesburg 2193, South Africa
Dr Carola Niesler, Department of Biochemistry, University of KwaZulu-Natal, Private Bag X01, Scottsville, Petermaritzburg, 3209, South Africa
Prof Kathy Myburgh, Department of Physiological Sciences, Stellenbosch University, Stellenbosch
Dr Johan Louw, Diabetes Discovery Platform, Medical Research Council, Tygerberg, South Africa
Publications (Since 2010):
van de Vyver M, Niesler C, Myburgh KH, Ferris WF. Delayed wound healing and dysregulation of IL6/STAT3 signalling in MSCs derived from pre-diabetic obese mice. Mol Cell Endocrinol. 2016 May 5;426:1-10.
Sanderson M, Sadie-Van Gijsen H, Hough S, Ferris WF. The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts. PLoS One. 2015 Aug 11;10(8):e0135358. doi: 10.1371/journal.pone.0135358. eCollection 2015. (Awarded the SEMDSA prize for the best paper in Endocrinology 2015-2016)
van de Vyver, M., Engelbrecht, L., Smith, C., Myburgh, K.H., 2015. Neutrophil and monocyte responses to downhill running: Intracellular contents of MPO, IL-6, IL-10, pstat3, and SOCS3. Scand J Med Sci Sports. doi:10.1111/sms.12497
Durcan PJ, Conradie JD, van de Vyver M, Myburgh KH. Identification of novel Kirrel3 gene splice variants in adult human skeletal muscle. BMC Physiology 2014, 14:11 doi:10.1186/s12899-014-0011-3.
van de Vyver M.*, Andrag E.*, Cockburn I. and Ferris W.F. Thiazolidinedione induced lipid droplet formation during osteogenic differentiation. Journal of Endocrinology, 223(2): 119–132, 2014
Aus T Ali, William F Ferris, Clement B Penny, Maria-Teresa van der Merwe, Barry F Jacobson, Janice E Paiker, Nigel J Crowther. Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots. JEMDSA 2013; 18(1): 58-64.
Sadie-Van Gijsen H, Smith W, du Toit EF, Michie J, Hough FS, Ferris WF. Depot-specific and hypercaloric diet-induced effects on the osteoblast and adipocyte differentiation potential of adipose-derived stromal cells. Mol Cell Endocrinol. 2012 Jan 2;348(1):55-66. (Awarded the Sanofi – Aventis Osteoporosis Award for the best original article published in the field of osteoporosis during 2011, and the SEMDSA Endocrinology Award for the best original publication in the field of Endocrinology during 2011)
Conradie MM, Cato AC, Ferris WF, de Wet H, Horsch K, Hough S. MKP-1 knockout does not prevent glucocorticoid-induced bone disease in mice. Calcif Tissue Int. 2011 Sep;89(3):221-7.
Ferris W.F, Marriott C.E, Ali T, Landy C, Campbell S.C and Macfarlane W.M. The Tumour suppressor Pdcd4 is major transcript that is upregulated during in vivo pancreatic islet neogenesis and is expressed in both beta cell and ductal cell lines. Pancreas. 2011 Jan;40(1):61-6. (Awarded the SEMDSA prize for the best basic science research article published on diabetes during 2011)
Ali AT, Ferris WF, Naran NH, Crowther NJ. Insulin resistance in the control of body fat distribution: a new hypothesis. Horm Metab Res. 2011; 43: 77-80
N. J. Crowther, W F Ferris. The impact of insulin resistance, gender, genes, glucocorticoids and ethnicity on body fat distribution. JEMDSA. 2010; 15 (3): 115-120
H. Sadie-Van Gijsen, N.J. Crowther, F.S. Hough, W.F. Ferris. Depot-specific differences in the insulin response of adipose-derived stromal cells. Mol Cell Endocrinol. 2010 Oct 26; 328 (1-2):22-7. (awarded the SEMDSA prize for the best basic science research article in Endocrinology
- Cockburn, IL., Ferris, WF., 2015 Pancreatic islet regeneration: Therapeutic potential, unknowns and controversy. S Afr J Sci; 111(7/8), http://dx.doi.org/10.17159/sajs.2015/20140369
- Sadie-Van Gijsen, H., Crowther, N.J., Hough, F.S., Ferris, W.F., 2013a. The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity. Cell. Mol. Life Sci. 70, 2331–2349. doi:10.1007/s00018-012-1211-2
- Sadie-Van Gijsen, H., Hough, F.S., Ferris, W.F., 2013b. Determinants of bone marrow adiposity: the modulation of peroxisome proliferator-activated receptor-γ2 activity as a central mechanism. Bone 56, 255–265. doi:10.1016/j.bone.2013.06.016
- Ferris, W.F., Crowther, N.J., 2011. Once fat was fat and that was that: our changing perspectives on adipose tissue. Cardiovasc J Afr 22, 147–154.