Group head
Name	Prof Michael Pepper
E-mail:	[email protected]
Telephone:	012 319 2190

 

A brief description of research activities

Cell-based therapy

Our research addresses diseases that contribute to South Africa’s disease burden including HIV, obesity, birth asphyxia and cancer. All of our work has a translational element. Our major focus is on adult stem cells, namely hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). With regard to HSCs, one of our main objectives is to use these cells to generate an HIV-resistant immune system. We have established a productive collaboration with Prof Roberto Speck (University of Zurich) and Prof Karl-Heinz Krause (University of Geneva) in Switzerland. Our initial objective has been to use a lentiviral-based approach to knock down CCR5, one of the two HIV co-receptors. We are also identifying other host targets that might be relevant. Our objective is to use this project to initiate a gene therapy platform, from which gene therapy projects for other diseases will follow. The HIV gene therapy project has several additional facets. These include the identification of primitive HSC populations, determination of the infectability of primitive HSCs by HIV, expansion techniques for HSCs, possible use of G-CSF-mobilized peripheral blood HSCs in addition to cord blood HSCs for gene therapy purposes, improvement in transduction efficiency, pre-and post-transplantation selection techniques, and the study of HLA diversity in southern African populations.

Gene therapy approaches will initially make use of autologous cell therapy products, meaning HSCs will be harvested from the patient living with HIV, followed by genetic manipulation and transfusion back to the patient (donor). HIV-infected patients will only be considered for receiving genetically-modified HSCs if their plasma viral load is undetectable and the HIV infection is well controlled using combination antiretroviral treatment (cART). However, it is important to understand the interactions between HSCs and HIV and how these interactions impact on HSC function. Thus another focus area in the group in to investigate the impact of HIV on haematopoiesis, included HSC/HIV interactions in people living with HIV, to study the mechanisms involved contributing to HIV-associated cytopenias in these patients (using both in vitro and experimental animal approaches) and to understand to what extent successful cART restores HSC function. A better understanding of these aspects may lead to improved strategies to ensure successful HSC transplants.

With regard to MSCs, our goal is to establish a clean room facility in order to provide cell therapy products for MSC clinical trials. A great deal still remains to be understood about MSC heterogeneity, differentiation capacity in vivo, homing properties, and optimal growth conditions in vitro including the elimination of xenogeneic products. With regard to heterogeneity, we are using single-cell transcriptomics in an attempt to understand the molecular basis of this heterogeneity. With regard to differentiation, our focus is on adipogenesis. To this end we have established multiparameter assays of adipogenesis which allow us to identify cells at various stages of differentiation and through a detailed assessment of the transcriptome, to understand the molecular basis of this process. The possible effect of MSCs on tumour growth is also being studied.

 

Genetics/genomics

Our second major area of interest is the human genome. Several projects are underway in these areas including identification of novel variants in monogenic disorder causative genes like CFTR in cystic fibrosis, identification of novel variants and validation of molecular diagnostic tools for cancer and several projects in the pharmacogenomics field.

In addition, we have initiated a multi-institutional programme on birth asphyxia, which includes the identification of novel biomarkers. This project will evolve over the next few years to become one of the major focus areas of the group.

 

Regulatory environment

Finally, a major component of our work will continue to address the ethical, legal and social implications/consequences of the work we are doing on stem cells and the human genome.

 

Current group members:

Name	Position	Qualification(s)	e-mail address
Prof MS Pepper	Group Head	MBChB, PhD, MD	[email protected]
Staff
Dr Melvin Ambele	Senior scientist	PhD	[email protected]
Dr Chrisna Durandt	Senior researcher	PhD	[email protected]
Ms Jeanne van Rensburg	Project Manager	MSc	[email protected]
Mrs Martie Madgwick	Senior Manager Assistant	Senior Certificate in typing and shorthand	[email protected]
Mrs Rita Swanepoel	Finance Officer	Senior Certificate Courses:  IP; Contract & Project Management	[email protected]
Mrs Candice Murdoch	Lab manager	MSc	[email protected]
PhD students
Juanita Mellet	PhD (Immunology)	MSc	[email protected]
Karlien Kallmeyer	PhD (Immunology)	MSc	[email protected]
Elize Wolmarans	PhD (Immunology)	MSc	[email protected]
Mqondisi Tshabalala	PhD (Immunology)	MSc	[email protected]
Nicolette du Plessis	PhD (Paediatrics)
Rosemary Kabahuma	PhD (Immunology)
Bukola Agbedare	PhD (Immunology)		[email protected]
Marcel Nel	PhD (Physiology)
Sulette Nel	PhD (Immunology)
MSc students
Catherine Wickham	MSc (Immunology)	BSc Honours	[email protected]
Candice Herd	MSc (Immunology)	BSc Honours	[email protected]
Carina da Silva	MSc (Immunology)	BSc Honours	[email protected]
Anastasios Athanasiadis	MSc (Immunology)	BSc honours
Aurona Gerber	MSc (Immunology)	BSc Honours
Simone Grobbelaar	MSc (Physiology)	BSc Honours
Co-supervision
PhD students
Johan Viljoen	PhD (Engineering)
Ahmad Haeri Mazanderani	PhD (Immunology)	MBChB	[email protected]
Victoria Damerell	PhD
Camille Castelyn	PhD
Nare Sekoba	PhD (Physiology)
MSc students
Karel de Bruin	MSc (Engineering)
Nomvuselelo Nyathi	MSc (Physiology)

 

Post-graduate students graduated in the past 5 years:

Name	Degree	Date of qualification
Ladislaus Adam	MSc (Immunology)
Chantel Gouveia	MSc (Reproductive Biology)
Carlo Jackson	PhD	April 2017
Carla Dessels	MSc	April 2017
Danielle de Villiers	MSc	April 2016
Jeanne van Rensburg	MSc	April 2016
Juanita Mellet	MSc	April 2015
Fiona van Vollenstee	MSc	April 2015
Antoinette Colic	Hons	April 2015
Karlien Kallmeyer	MSc (Immunology)	April 2015
Co-supervision
Melanie Skeen	MSc	April 2015
Renier Myburgh	PhD	Jan 2015
Dominique Levigne	PhD	Oct 2014

 

Collaborations within the ICMM

Name	Affiliation	Project
Prof Ronnie Anderson	Immunology	MSC immunomodulation
Prof Pieter de Villiers	Data Fusion Group	Cystic fibrosis, cell biology
Prof Andrew Leisewitz	Companion Animal Studies	Babesiosis
Prof Theresa Rossouw	Immunology	HIV gene therapy
Prof Willie van Heerden	Oral Pathology	Head and Neck Cancers
Prof Roger Pool	Haematology	HIV-associated cytopenias

 

National and international collaborations

National collaborations

Name	Affiliation	Project
Prof Michele Ramsay	Wits	SAHGP
Prof Melodie Slabbert	Unisa	ELSI
Prof Ames Dhai	Wits	ELSI
Prof Himla Soodyall	Wits	San genome
Dr Marco Zampoli	UCT	Cystic fibrosis

 

International collaborations

Name	Affiliation	Project
Prof Roberto Speck	University of Zurich, Switzerland	HIV-resistant immune system
Prof Karl-Heinz Krause	University of Geneva, Switzerland	HIV-resistant immune system
Prof Brigitte Pittet	University of Geneva, Switzerland
Dr Ali Modaressi	University of Geneva, Switzerland

 

Visiting guests during 2018

Dr Farhad Imam (Gates Foundation)

 

Updated 2019/03/06