PHARMACOGENOMICS AND DRUG METABOLISM RESEARCH GROUP
Executive Summary

The Pharmacogenomics and Drug Metabolism Group (PharmGx), in the Division of Human Genetics, Department of Pathology & Institute of infectious diseases and molecular medicine (IDM), in the Faculty of Health Sciences, University of Cape Town is dedicated to addressing the global gap in precision medicine by leveraging the unparalleled African genetic diversity, the deepest source of human variation, to understand, predict, and ultimately optimize therapeutic drug response. PharmGx also hosts the UCT/SAMRC Platform for Pharmacogenomics Research and Translation Unit. The research, led by Professor Collet Dandara, meticulously investigates how inherited genetic variation in genes coding for critical enzymes involved in drug metabolism (e.g., cytochrome P450 enzymes), drug transport, including epigenetic factors, and microbial profiles, dictates patient outcomes in the face of complex treatments required by the quadruple burden of disease in Africa, including HIV/AIDS, hypertension, cardiovascular diseases (e.g., dyslipidaemia),and the pharmacogenomics of herbal medicines. PharmGx is also involved in researching the genetics of chronic kidney diseases (CKD) including rare diseases. Aligned with the SAMRC’s mandate for technology transfer and the University of Cape Town's mission of using outstanding research and scholarship to advance a more equitable and sustainable social order, PharmGx is committed to bench-to-bedside translation, moving findings into actionable clinical tools that secure precision dosing and dramatically reduce adverse drug reactions. Crucially, PharmGx underpins this translational work through robust capacity building, including the supervision of future scientific leaders (Hons/MSc/PhD students, postdoctoral fellows) and flagship training initiatives aimed at strengthening research and training capacity across the African continent. Our definitive goal is the establishment of routine, pre-emptive pharmacogenomic testing across the continent, ensuring safe and effective tailored therapies for all.

 

  1. Introduction: The Global Pharmacogenomic Gap and the African Imperative

The effective administration of therapeutic drugs hinges upon understanding how an individual’s genetic makeup influences the efficacy and safety profile of a compound including herbal medicine. While pharmacogenomics (PGx) has gained prominence in global medicine, a significant scientific deficit exists regarding data derived from African populations. The PharmGx group at UCT was established to rigorously address this disparity, framing it not merely as a local problem but as a critical global scientific opportunity.  

 

1.1 Establishment of Institutional Authority and Mandate

The Pharmacogenomics and Drug Metabolism Group is positioned strategically within the Division of Human Genetics, operating under the institutional umbrella of the Institute of Infectious Disease and Molecular Medicine (IDM) at the University of Cape Town (UCT). This institutional placement immediately links the unit's highly specialized genetic research to the major infectious and non-communicable disease burdens prevalent across Africa. 

 

Crucially, the group’s activities are co-recognized by the Medical Research Council of South Africa (SAMRC), signifying its national strategic importance as seen from the awarding of the “UCT/SAMRC Pharmacogenomics Research and Translation unit”. The SAMRC mandate explicitly requires the institution to improve the health and quality of life for South Africans through "research, development, and technology transfer". This aligns perfectly with UCT's broader academic mission, which commits the university to engaging with the key issues of our natural and social worlds through outstanding teaching, research and scholarship. Therefore, the group's research output is designed not just for academic pursuit but to advance a more equitable and sustainable social order by translating findings into the health system. This authoritative backing by both UCT and the SAMRC must be conveyed in all public messaging to establish immediate credibility and gravitas.

 

2. The Scientific Imperative: Unmatched Genetic Diversity

The foundation of the group’s work rests on the recognition that African populations possess the most profound genetic diversity worldwide. This diversity is the source of unique human genetic variation, presenting a monumental challenge to standard drug regimens that are often optimized based on less diverse genomic pools, particularly of European and Asian ancestry. When drug protocols are developed outside the African genomic context, the high intrinsic variability among African patients leads to unpredictable therapeutic responses, elevated rates of adverse drug reactions (ADRs), and increased treatment failure.

 

This variability, however, is not simply a challenge; it is the fundamental engine of discovery. The genetic landscape of Africa harbours novel genetic variants that are likely to provide critical "clues to genetic variants that make certain individuals more susceptible to disease/infection than others". Therefore, the unit's existence is propelled by a strategic ambition: converting the clinical risk associated with high genetic variation into an unparalleled scientific opportunity to identify and characterize novel pharmacogenes, susceptibility genes, leading to globally transformative health insights. Without focused research addressing this immense genetic reservoir, global pharmacogenomic knowledge remains incomplete, and healthcare delivery in Africa remains sub-optimal.

2. PharmGx Core Focus: Science, Scope, and Leadership

The scientific agenda of PharmGx is meticulously constructed to address the most clinically consequential aspects genetic variation as it pertains to both disease predisposition and drug response among African patients. The approach combines fundamental genetic studies with a pragmatic consideration of the real-world healthcare context.

Addressing Africa’s Complex Disease and Treatment Profile

The research scope of PharmGx is acutely relevant to the unique public health context of Africa. The continent is characterized by a "quadruple burden of disease", encompassing communicable diseases (like HIV/AIDS and Tuberculosis), non-communicable diseases (NCDs), trauma, and socio-economic conditions. This complexity necessitates the frequent use of combination therapy, the co-administration of multiple drugs (e.g., highly active antiretroviral therapy (HAART) alongside NCD medications or anti-tuberculosis regimens). This combination therapy environment significantly amplifies the risk of adverse outcomes because of complex drug-drug and gene-drug interactions. Furthermore, the group takes a pragmatic approach to healthcare realities by including research into the pharmacogenomics implications of using herbal medicinal plants. Traditional herbal medicines are frequently used concurrently with conventional pharmaceuticals. These herbal components often contain compounds that can induce or inhibit the same key metabolic enzymes, further complicating drug metabolism and potentially altering the efficacy or toxicity of prescribed drugs. Including this aspect ensures that the group’s research output is relevant to the entirety of patient health practices in Africa.

The Multi-Omics Approach to Therapeutic Response

To develop truly predictive models of drug response, the PharmGx unit adopts a comprehensive systems-biology approach that extends beyond inherited genetic variation. The unit’s mandate includes identifying not only inherited genetic variations, but also epigenetic changes and microbial profiles associated with interindividual differences in treatment response. This multi-omics focus is critical. Epigenetic changes, such as DNA methylation, can regulate the expression levels of drug-metabolizing enzymes without altering the underlying DNA sequence. Similarly, the composition and function of the gut microbiome (the microbial profile) can directly influence drug efficacy and toxicity, as microbes themselves can metabolize drugs. By incorporating these environmental and biological modifiers alongside genomics, the group is transitioning towards a holistic patient profiling methodology, which is essential for achieving the ambitious goal of genuinely predictive and preventative personalized medicine in a population where environmental factors and disease co-morbidities are prevalent

  1. The Vision of Pre-emptive Pharmacogenomic Testing and Capacity Building 

The visionary goal of the PharmGx Group represents a fundamental shift in clinical practice: leveraging pharmacogenomics to tailor medications specifically for defined populations, culminating in the establishment of "pre-emptive, one-off testing becoming routine among patients". This shift from reactive drug adjustment (e.g., changing a prescription after an adverse reaction occurs) to proactive risk management (preventing the adverse reaction before the first dose is administered) is the definitive measure of the group’s long-term success. Routine pre-emptive testing would dramatically reduce the chances of severe adverse drug reactions to prescribed medications, saving lives and vastly improving health outcomes, particularly within the quadruple disease burden context where treatment complexity is high. However, realizing this ambitious clinical vision requires acknowledging the immediate operational reality, which heavily relies on capacity building and the systematic characterization of "many more pharmacogenes in African populations". Professor Dandara has been recognized for his work in Human Capacity Development and has successfully supervised numerous MSc/PhD students. Furthermore, the unit runs flagship training initiatives, such as short courses, to commit to strengthening research and training capacity within institutions and regions across Africa. This dual focus, scientific discovery and educational development, establishes a clear link between the immediate task and the long-term clinical objective (systemic implementation). 

 

Summary of Current Projects
  • Pharmacogenomics of Anti-retroviral therapy
  • Pharmacogenomics of coumarins
  • Pharmacogenomics of statins
  • Pharmacogenomics of hypertension and preeclampsia
  • Schizophrenia pharmacogenomics
  • Discovery of HIV latency activators (Natural products)
  • Pharmacomicrobiomics
  • Genetic susceptibility to breast, and oesophageal cancer
  • Genetic susceptibility to cytomegalovirus (CMV) acquisition and transmission
  • Chemotherapeutic drugs and herbal compounds and their effects on gene expression profiles of drug metabolizing enzymes
  • HIV and HPV co-infection in cervical cancer patients
TEAM
Principal Investigator
MEMBERS
PhD Students

MSc Students

 

Associate Members/Collaborators
  • A/Prof Phumla Sinxadi - Associate Professor in the Division of Clinical Pharmacology, Department of Medicine, University of Cape Town
  • A/Prof Erika Jones - Associate Professor in the Division of Nephrology and Hypertension, University of Cape Town and Groote Schuur Hospital
  • A/Prof Dirk Blom - Head of the Division of Lipidology, University of Cape Town and Lipid Clinic at Groote Schuur Hospital.
  • A/Prof Sipho Dlamini - Associate professor in the division of Infectious Diseases & HIV Medicine, Groote Schuur Hospital.
  • A/Prof Bianca Davidson - Associate Professor at university of Cape Town and Consultant Nephrologist Groote Schuur Hospital
  • Prof Brian Rayner - Head and Director of Research of the Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town
  • Prof Mpiko Ntsheke - Helen and Morris Mauerberger Professor and Chair of Cardiology, University of Cape Town.
  • Dr More Stuart - Head of the Division of Nuclear Medicine, Groote Schuur Hospital and the University of Cape Town
  • Dr Michelle Skelton – Program manager, H3Africa Bionet
  • Dr Elizabeth Kampira – Lecturer, Malawi College of Health Sciences
  • Dr Kudakwashe Mhandire – Lecturer, University of Zimbabwe
  • Dr Nyarai Desiree Soko – Senior lecturer, Harare institute of technology
  • Dr Kevin Dzobo – Senior Research Scientist, ICGEB
  • Dr Victoria Nembaware – Project Manager, SADaCC, University of Cape Town
  • Sarudzai Muyambo (BSc, MSc)- PhD student -University of Zimbabwe
ALUMNI