​​

CRG.jpg

Group leader: 

Prof Anna-Mart Engelbrecht

Prof AME.jpg

Biographical details:

Anna-Mart Engelbrecht is currently professor in the Department of Physiological Sciences at Stellenbosch University. She was born in Pretoria, grew up in the Western Cape and matriculated in DF Malan High School in Bellville. She completed a BSc (Hons) in Physiology at Stellenbosch University, a MMedSc (cum laude) at the University of the Free State and received her PhD in 2005 at Stellenbosch University. She received several prestigious awards which include the Dean’s and Senate’s Medals as well as the Gencor Bronze Medal from the University of the Free State, the Marie Curie Scholarship of the European Union and the Rector’s award for excellence in research from Stellenbosch University. Twelve MSc and four PhD students completed the degrees under her supervision; she currently serves as promotor and co-promotor for 10 PhD students. She serves on the editorial board of the International Journal of Biomedical Sciences and referees regularly for international journals which include Molecular and Cellular Biochemistry, Pharmacological Research, Apoptosis, Cancer Letter, European Journal of Clinical Investigation and Physiological Research. She has published 82 peer reviewed, research articles and presented invited lectures at national and international conferences. She established the Disease Signaling Group, which later evolved into the Cancer Research Group (CRG) where they investigate metabolic pathways in cancer cells and mechanisms in chemotherapy-induced damage to the heart and skeletal muscle.

Research Focus: 

Cancer does not distinguish between race, gender, age or socioeconomic position; it is merciful to no-one and despite the political will driving a concerted global effort, only marginal progress has been made in the War against Cancer. One aspect which contributes to the poor progress in the management of cancer relates to the severe collateral damage associated with the current treatment strategies. Although anthracyclines such as doxorubicin has proven to be of the most successful approaches to cancer treatment, it induces various side effects such as nausea, vomiting, hematopoietic suppression and cumulative, dose-dependent cardiac toxicity. However, this is not the only challenge that researchers and clinicians are faced with; cancer cells are becoming increasingly resistant to chemotherapy-induced cell death. The specific focus of our research is to explore new avenues of chemotherapy and adjuvant treatments that would favour the use of lower chemotherapy concentrations with less side-effect to normal healthy cells, while maintaining satisfactory levels of cancer cell death.

Current Student​s and Proj​ects:

PhD students: 

Serum amyloid A and Inflammasome activation: A link to cancer progression?

 Carla Fourie.jpg 

Carla Fourie: PhD student, email: 18341683@sun.ac.za

Breast cancer research has been my main focus area since my honour's year in the CRG group. I am mostly interested in signaling mechanisms and pathways that influence breast cancer growth and development. The aim for my PhD is to determine the role of Serum amyloid A (SAA) and inflammasome activation in breast cancer progression as well as understanding the interaction between cancer cells and other cell types in the tumour microenvironment.

The effects of serum-amyloid A on autophagy and autophagy-dependent epithelial-mesenchymal transition in breast cancer cells

 Manisha du Plessis.jpg 

Manisha du Plessis, PhD student, email: 18971040@sun.ac.za

My primary area of interest is the signaling mechanisms involved in tumor initiation and cancer progression. The goal for my PhD is to determine which role Serum amyloid A (SAA) plays in autophagy induction or inhibition in breast cancer cells, and how the modulation of autophagy by SAA regulates metastasis.  Cytokines, growth factors and acute phase proteins present in the tumour microenvironment regulate inflammatory responses and alter crosstalk between various signalling pathways involved in the progression of cancer. Serum amyloid A (SAA) is a key acute phase protein secreted by the liver during the acute phase response (APR) following infection or injury. However, cancer and cancer-associated cells produce SAA, which when present in high levels in the tumour microenvironment contributes to cancer initiation, progression and metastasis. SAA can activate several signalling pathways which are also known modulators of the intracellular degradation process, autophagy. Dysregulation of autophagy can induce malignant transformation through oxidative stress, endoplasmic reticulum (ER) stress and DNA damage. On the other hand, autophagy can promote cancer survival during metabolic stress, hypoxia and senescence. I am investigating the effects of SAA on autophagy in breast cancer cells and the downstream effects on metastasis.

Investigating the anti-cancer effects of silver/gold nanoparticles stabilised by phosphine ligands in an in vitro and in vivo breast cancer model

 Claudia Christowitz.jpg

Claudia Christowitz, PhD student, email: claudiac@sun.ac.za

I have chosen to be in CRG because of my interest in cancer biology research, especially focusing on how tumours respond to or resist treatment.

 

An Investigation into the role of Serum Amyloid A in breast cancer

Niel Olivier.jpg

Niel Olivier, PhD student, email: dwo@sun.ac.za

I have always found it heart-breaking how diseases can reshape a person and those around them, many times not for the better. As such, from an early age, I wanted to understand the underlying mechanisms of disease, leading me to pursue studies in Biochemistry and Physiology, with cancer among the subjects hitting closest to home. My PhD focused on the role of a small, immensely important serum protein, called Serum Amyloid A (SAA), in the pathogenesis of breast cancer. Under physiological conditions, this protein is important in many inflammatory processes necessary for the maintenance of homeostasis following tissue damage or infection. However, from the literature, its presence in the blood of cancer patients seemed to indicate a pathological contribution, a hypothesis my project confirmed towards the end of 2020. This follows from data on tumor-bearing mice lacking systemic SAA, showing an increase in DNA repair within the tumor, in addition to lower levels of tumor necrosis – a process unequivocally associated with a worse prognosis. I hope this data will eventually lead to medical intervention and the saving of lives.

MSc students: 

The Tumour Microenvironment: The impact of breast cancer on the endothelium

Atarah Rass.jpg 

Atarah Rass, MSc student, email: 19142609@sun.ac.za

The tumour microenvironment is formed as a result of the interactions between cancer cells and their surrounding stroma, and ultimately promotes cancer progression and drug resistance. The tumour microenvironment is comprised of several types of cells with pro-tumour phenotypes contributing to and promoting conditions which favour cancer growth and metastasis. Endothelial cells are the cells that comprise the blood vessel walls. They are therefore central to every organ within the body and furthermore serve as key members of the stroma and thus the tumour microenvironment. Within the tumour microenvironment endothelial cells are altered to adopt a tumour endothelial cell phenotype. As a result of this phenotypical change, they are equipped to promote cancer growth, metastasis and drug resistance. Cancer-related research largely focuses on the influence of the endothelium on cancer and in breast cancer studies, the tumour endothelial phenotype has been poorly under-researched. Broadening the current understanding of the above provides insight into new treatment avenues and therapeutic strategies. This project aims to investigate how breast cancer impacts the endothelium, and to elucidate the tumour endothelial cell phenotype in breast cancer.

 

The functional implications of the novel variant, c.1018A>G p.N340D in breast cancer

Michelle van der Merwe.png 

Michelle van der Merwe, MSc student, email: 20331193@sun.ac.za

Cancer cells are the rebel cells of our body. I have always been interested in why these cells turn against us. Being in the CRG enables me to explore just that. We are constantly trying to understand cancer cells better and thinking of new ways to trick them.


​A comparison of bio-identical and non bio-identical hormones used for hormone replacement therapy (HRP) in the risk of developing breast cancer.

Kamano Mochoele.jpg

Kamano Mochoele, MSc student, e-mail: 18973248@sun.ac.za

Menopausal hormone therapy or replacement therapy (MHT) has been used for the relief of menopausal symptoms. Since the results of the 2001 Woman's Health initiation (WHI) study, there has been a decline in the long-term use of MHT to alleviate postmenopausal symptoms. There is a misconception about the use of MHT and its role in the increased risk of developing cancer. The study showed that a certain combination; conjugated equine estrogen (CEE) + medroxyprogesterone (MPA), increase cancer risk, however there is a misconception that all MHT's increase cancer risk. Bioidentical hormones (BH's) are considered natural and safe because they are molecularly identical to endogenous hormones, unlike synthetic hormones which have different chemical structures. Evidence shows that bioidentical hormone therapy (BHT) decreases menopausal symptoms and improves quality of life, however there is no definitive research that concludes their safety in relation to the risk of developing cancer. The aim of her study is to determine if the use of bioidentical hormone therapy decrease the risk of cancer in menopausal women?

Recent student publications:

  • Christowitz, C., Davis, T., Isaacs, A., Van Niekerk, G., Hattingh, S., Engelbrecht, AM., 2019. Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model. BMC Cancer;19(1): 757.doi: 10.1186/s12885-019-5939-z.
  • Du Plessis, M., Davis, T., Loos, B., De Villliers, JS., Pretorius, E & Engelbrecht, AM., 2021. Molecular regulation of autophagy in a pro-inflammatory tumour microenvironment: New insight into the role of serum amyloid A. Cytokine and Growth factors Reviews. doi.org/10.1016/j.cytogfr.2021.01.007
  • Fourie, C., Davis, T., Kriel, J & Engelbrecht, A-M., 2018. The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells. Experimental cell Research: 15; 381(2):280-287.
  • Fourie, C., Davis, T., Shridas, P., De Villiers, WJS & Engelbrecht, A-M., 2020. Serum amyloid A and inflammasome activation: a link to breast cancer progression? Cytokine and Growth factor reviews: https://doi.org/10.1016/j.cytogfr.2020.10.006.
  • ​Van der Merwe, M., Van Niekerk, G., Botha, Alf & Engelbrecht, AM, 2021. The onco-immunological implications of Fusobacterium nucleatum in breast cancer. Immunology Letters:232;60-66.