Research Teams and Expertise

Cancer modelling, dormancy and proliferation

 Prof Werner Cordier
(Research Leader)
Prof Duncan Cromarty Prof Vanessa Steenkamp

Collaboration with: Dr Iman van den Bout (Physiology, UP)

 

Development of molecules that display anticancer compounds have typically been tested in a traditional culturing system, where cells are grown as monolayer cultures. Unfortunately, these culture methods fail to replicate the complex structure of cancer in vivo, including the ability of some to enter dormant phases and become resistant to drug treatment. Through the use of three-dimensional culturing techniques, particularly the liquid overlay method, cancerous cells are grown as a spheroid structure, where cells attach to one another instead of the culture surface. In doing so, these spheroids display characteristics that are more representative of the in vivo environment, including reduced drug susceptibility and the ability to enter dormancy. The research team focuses on establishing spheroidal models of cancer (primarily triple-negative breast carcinoma), and assessing their differential responses to anticancer molecules through investigating cytotoxicity, proliferation and proteomic changes.

Students: Mr KN Ncube (PhD); Ms Cara de Moura (MSc).

Drug discovery and development

Prof Werner Cordier
(Research Leader)
Prof Duncan Cromarty
(Research Leader)
Prof Vanessa Steenkamp
(Research Leader)

Drug discovery platforms are available within the department, focusing on evaluating the biologies activities of samples from various sources, including natural, synthetic and in silico-designed. This platform bleeds into the various disease states under investigation by the department, and thus is led by different individuals.

Health professions education


    

Collaborations with:

  • Prof Pieter du Toit (Humanities Education, UP)
  • Prof Dianne Manning (Health Sciences, UP)
  • Dr Irene Lubbe (Education Innovation, UP)
  • Ms Clarisa Sutherland (Anatomy, UP)
  • Ms Josephine Najjuma (Mbarara University of Science of Technology, Uganda)
Prof Werner Cordier

Health professions education concerns itself with providing Students with the competencies and attributes required to function with the various health professions disciplines. Literature is rife with the potential implications of education on the quality of the health sector, making it an important area to place focus on so that patients may one day receive high quality treatment. Given the different ways in which health professionals are trained, the research team focuses on investigating the implications of curricular choices on the way competencies are gained, interpreted or benefited from. Aspects such as curriculum design, constructive alignment and innovative androgogy (including game-based learning and debating) are currently being evaluated within the parameters of pharmacology modules.

Hepatotoxicity

Collaborations with:
Dr Tracey Hurrell (Karolinksa Institutet)
Prof Duncan Cromarty
(Research Leader)
 

The main emphasis of Prof Duncan Cromarty's research for the next two to three years would specifically address proteomic challenges associated with hepatotoxicity assessment in both in vitro and in vivo situations. The main outcome is to develop a reliable model for early detection of hepatotoxic effects that include intrinsic toxicity, metabolic activated drug toxicity and secondary effect toxicity where the initial hepatic damage results in relatively slow but irreversible toxicity effects. Such aspects are addressed by cell culture, flow cytometry and mass spectrometry to assess drug efficacy and toxicity, and proteomic analysis to identify possible drug targets and effects of lead compound treatment. The research area collaborates widely locally and internationally with research teams.

Students: Mr A Ellero (PhD); Mr C Mashaba (MSc).

Medical pharmacology

Prof Kim Outhoff
(Research Leader)

Dr Morné Strydom

The MPharmMed students conduct clinical research in diverse therapeutics areas including diseases, rheumatology, infectious disease, endocrinology, cardiovascular disorders, mental health and gynaecology.

Nanoparticles within drug discovery and delivery


 

Collaboration with:

  • Prof Mary Gulumian (NIOH/WITS)
  • Dr Charlene Andraos (NIOH/WITS)
  • Dr Melissa Vetten (NIOH/WITS)
Prof Werner Cordier
(Research Leader)
Prof Vanessa Steenkamp  

Nanoparticles, or particles that fall within the nanometer scale, are used for various purposes in medicine. Many functionalised or non-functionalised nanoparticles have properties that make them useful in direct therapy, or potentially assist with the delivery of other molecules within physiological systems. The research team focuses on determining the potential bioactivities within cellular models, particularly those that are cultured within three-dimensional environments. Bioactivity evaluated comprise the various ways in which cytotoxicity may be incurred (either in a cancerous or non-cancerous state), as well as the mechanisms by which such nanoparticles are taken up into cells.

Students: Ms M Petzer (MSc).

Neurodegeneration and neuroprotection

 


 

Collaboration with:

  • Dr Jenny-Lee Panayides (CSIR)
  • Dr Darren Riley (Chemistry, UP)
Prof Vanessa Steenkamp
(Research Leader)
Prof Werner Cordier  

Life expectency has steadily been increasing over the past few decades, and as such, more and more neurological decline has been noted within our population. Diseases, such as Alzheimer's disease and Parkinson's Disaese, is increasing within the South Africa population, and as there is currently no cure, these have become prominent focus areas for the Department of Pharmacology. The research team places emphasis on researching the models used to evaluate neurodegeneration, trying to increase their representation of the true molecular milieu in such diseases. Furthermore, these platforms are being used to evaluate the potential neuroprotective abilities of samples from various sources, including herbal remedies, as well as synthetic and in silico-designed molecules.

StudentsMr N de Beer (PhD); Ms L Maboko (PhD).

Phytopharmacology

 


 

 

Collaboration with:

  • Prof Paul Steenkamp (UJ)
  • Dr Sechaba Bareetseng (CSIR)
Prof Vanessa Steenkamp
 
Prof Werner Cordier Dr Marissa Balmith Dr Brian Flepisi

Phytopharmacology, or plant-based medicine, is a research area that is of specific relevance in a country such as South Africa. It has been estimated that approximately 80% of the African population in developing countries rely on complementary and alternative medicines, including herbal remedies, as primary health care. Dating back generations, plants have been used to treat various ailments and are a rich source of phytochemicals, which has led to the discovery of approximately 30% of drugs currently on the market. The team is focused on the determination of biological activities and toxicities of traditional herbal remedies related to their ethnomedicinal use, and to contribute to the understanding of the mechanistic action of these remedies in the treatment of disease. Another focus of this team is to identify, isolate and test phytochemicals from bioactive plants for a wide platform of diseases with no cure, ranging from cancer, neurodegenerative diseases, and wounds.

Students: Ms N Nzama (MSc); Ms C Van Ballegooyen (MSc).

Wound healing


 

Prof Duncan Cromarty
(Research Leader)
Prof Vanessa Steenkamp

Wound healing is a dynamic, complex process consisting of distinct, sequential, but overlapping phases. In an acute wound, healing proceeds in a predictable fashion, but can be hindered by external factors and patient conditions, resulting in the formation of a chronic wound. Chronic wounds have a negative impact on a patient's quality of life, which is estimated to be comparable with that of other chronic diseases. Consequently, wounds require immediate and effective treatment to prevent morbidity and mortality. Current pharmacotherapy of wounds is aimed at circumventing the effects of factors such as oxidative damage and microbial infections in wounds; these may hinder the progression of the healing process, compounding the formation of a chronic wound. These treatments are accompanied by numerous side effects and increased resistance, which is evident in the lack of a true gold standard for wound healing. The wound healing research group, headed by Prof Duncan Cromarty, is focused around the characterisation of chronic wounds and the development of emerging therapies, which rely on the stimulation of natural wound healing processes. This is achieved through the use of in vitro and in vivo studies which are coupled to cutting edge proteomic, metabolomic and lipidomic techniques.

StudentsMs S Mlambo (PhD); Ms H Parkar (PhD); Ms TM Lebepe (MSc), Mr J Snyman (MSc).  

Infectious diseases

 
Prof Natalie Schellack  

Her research interests are centred on the broad area of clinical pharmacy as related to paediatrics, ototoxicity and infectious diseases (e.g. TB and HIV). More specifically interested in quantifying antimicrobial utilisation data, pharmacokinetic and dynamic levels of antibiotics in blood levels. More recently her research area has been more focused on finding innovative ways of measuring antimicrobial utilisation using health technology. 

Prof N Schellack is a NRF rated researcher (C2).

Her publications can be accessed at Google Scholar  https://scholar.google.co.za/citations?hl=en&user=TC_vFwcAAAAJ&view_op=list_works&gmla=AJsN-F5OL67Zbd0GlNYxeQ1O4qqEUt7lLKQP2Inbk-s71hWV-klRnx1uSa4En5aEU2hkR8XrSxJgPRifSkCo0TKtqP735nq8RsG2P9Na6Qz2IUbI7OA6nxg

Research gate score is 33.45 and the information can be obtained at https://www.researchgate.net/profile/Natalie_Schellack?ev=prf_highl

She collaborates both nationally and internationally based on the respective project.

In silico studies

 

 

Dr Marissa  Balmith Dr Brian Flepisi  

Our research scope covers a wide range of computational and molecular modelling research areas with main focus on biological systems and drug design approaches. The main interest of our research is related to the design and study of biologically and therapeutically oriented targets by employing the applications of computational methods to the study of problems of chemical and biochemical reactivity. This includes mechanistic pathways, design of enzyme inhibitors and exploring the binding and catalytic theme of the designed targets and adopting sophisticated computational approaches to understand protein structures and functions.

Cancer Metastasis

 

 

 
Dr Marissa  Balmith Dr Brian Flepisi  

To understand how cancer develops and progresses, researchers first need to investigate the biological differences between normal cells and cancer cells. Our research focuses on the mechanisms that underlie fundamental processes such as cell growth, the transformation of normal cells to cancer cells, and the spread (metastasis) of cancer cells by i) characterising the components of the tumor microenvironment and determine their individual and collective influences on tumor progression and regression, ii) understanding the mechanisms by which cancer cells communicate with surrounding normal cells and interact with them to promote tumor growth, and iii) understanding how cells and tissues in other parts of the body interact with cancer cells to prevent or promote metastasis. Metastasis remains a challenge in terms of treatment and is usually the primary cause of morbidity and mortality in cancer patients, accounting for 90% of cancer deaths. Thus there is an urgent need for new drugs for treatment and or prevention of cancer metastasis. Our research focuses on alleviating the cancer-disease burden through the identification of molecules mediating metastasis, elucidating their expression levels, and to determine the cytotoxicity of inhibitors against these target molecules by selecting inhibitors of those functions.

Neuropharmacology

 
 
 
Dr Marissa  Balmith Dr Brian Flepisi  

The blood brain barrier (BBB) is a collection of anatomical barriers and transport systems within the endothelium of cerebral vasculature. It is the tightest endothelial barrier in the human body, with high transendothelial electrical resistance and low permeability, owing to the properties of the endothelial cells lining the cerebral vasculature. It confers strict, selective control over the transport of substances into and out of the brain parenchyma. The BBB is responsible for preventing the entry of neurotoxins, metabolic waste, cells and pathogens present in the peripheral circulation into the central nervous system (CNS). The BBB is subject to disruptions, which may lead to dysfunction. Loss of BBB integrity is a feature of a multitude of neurological diseases and results in increased permeability, however, the mechanism in which this is accomplished is highly elusive. Cancer metastasis to the CNS functionally and structurally alters the BBB. As a result, BBB permeability increases, thus, allowing the entry of potentially harmful substances into the nervous system. Our research group aims to investigate the relationship between metastatic cancer cells and the BBB.

Snakebite envenoming

 

Dr Morné Strydom

(Research Leader)                                                                  

Snakebite envenoming has been classified by the World Health Organization (WHO) as a neglected tropical disease that is responsible for tremendous suffering, disability and mortality around the globe. The typical encounter between human and snake is usually unpleasant and frightening for both parties, which may end in devastation for both, driven by mutual fear. Humans often sustain a snakebite by accidently stepping on it in the field, or by threating it by trying to corner and catch it. Due to the lack of fast and reliable snake identification at hospital level, most cases of snakebite appropriate clinical management require reliable identification of a distinctive clinical syndrome based on epidemiological, clinical and laboratory data. It is interesting to note that all venomous snakebites will affect blood coagulation to some or other degree, implicating a haemotoxic profile for all venomous snakes at various grades of intensities. This gives us the opportunity for a more in-depth investigation of this common ground phenomenon, which may give us better insights into possible species specific differences by assessing their effects on human blood. This has the potential to bring us closer to snake identification on a biochemical level.

Our research team study the effects of snake venom on blood cell ultrastructure and coagulation in humans, with special reference to diagnostic markers and toxicology, by incorporating various techniques including haematology analysers, thromboelastography (TEG), global thrombosis test (GTT), turbidimetry, microscopy (light, confocal and scanning electron), proteomics and metabolomics. The aim of our research is to investigate the effects of venom from various Southern African snake species which are known to deliver a clinical significant bite and envenomation, to profile and compare its effects on blood cell ultrastructure and coagulation, in order to access whether the results could be of diagnostic value to confirm envenomation and potentially snake identification in future.

Collaboration with:

  • Dr Janette Bester (Department of Physiology, Faculty of Health Sciences, University of Pretoria, South Africa)
  • Prof Resia Pretorius (Physiological Sciences Department, Faculty of Science, Stellenbosch University, South Africa)

Publication:

Strydom MA. et al. The effect of physiological levels of South African puff adder (Bitis arietans) snake venom on blood cells: an in vitro model. Sci Rep 6, 35988 (2016). https://doi.org/10.1038/srep35988

Quantification of drug molecules in human breast milk

 
 
 
Dr Sarel Brand Prof Duncan Cromarty  
Breast milk represents the most important resource in promoting early childhood health, and exclusive breastfeeding for infants is encouraged. Mothers of premature babies or who do not produce enough milk often make use of donated breastmilk where possible. Considering the scarcity of donated breastmilk, it would be ideal to accept and distribute milk from as many donors as possible. However, the safety of donated milk for consumption by developing infants sourced from donors undergoing drug therapy needs to be ensured. Our research is focused on developing and validating LC-MS/MS methods to quantify numerous common drugs, specially neuroactive drugs, and their active metabolites in donor breastmilk samples. By doing this, we aim to determine pharmacokinetic parameters to allow modelling to determine whether breastmilk from donors undergoing various drug therapies may be considered safe for premature baby and infant feeding. 
 
 

 

 

Published by Magdalena Swart

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