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Pharmacogenomics

Overview

Pharmacogenomics and Cancer Research Group

Principal Investigator:

Associate Professor Collet Dandara [BSc, BSc (Hon), PhD]

PhD Students:

Marelize Swart [(BSc, BSc (Hon), Msc], Nyarai Soko [BSc, BSc (Hon), MSc], Donald Tanyanyiwa

MSc Students:

Luke Kannemeyer [BSc, BSc (Hon)], Naseeha Hassen [BSc, BSc (Hon), MSc], Bafokeng Mpeta [BSc, BSc (Hon)], Kamogelo Lebeko [BSc, BSc (Hon)]

Hons Students:

Jonathan Evans [BSc]

NRF supported Interns:

Gavin Pharo [BSc, BSc (Hon)], Annesinah Hlengiwe Moloi [BSc], Anathi Jongilanga [BSc]

External Students:

Mr. Riaan Reay, Adjunct Professor Yasmien Jeenah

Associated Members:

Michelle Skelton[BSc, BSc (Hon), MSc, PhD, Manager at H3Africa Bionet]

Elizabeth Kampira[BSc, MSc, PhD, Lecturer at the Malawi College of Health Sciences]

Kudakwashe Mhandire[BSc, BSc (Hon), MSc, PhD student at University of Zimbabwe]

Doreen Duri[BSc, BSc (Hon), MSc student at the University of Zimbabwe]

Information on current postgraduate positions: please email; collet.dandara@uct.ac.za

Research focus/interests

The Pharmacogenomics and Cancer Research Group (PharmGx) focuses on understanding the genetic basis for inter-individual differences with respect to human susceptibility to disease, differential response to treatment, presentation of drug toxicity and cancer susceptibility. The group uses molecular biology techniques to investigate genetic variation in genes coding for drug metabolising enzymes (cytochrome P450, glutathione S-transferases, sulfotransferases, UDP-glucuronosyltransferases, alcohol dehydrogenases, aldehyde dehydrogenase and N-acetyltransferases), drug transporters (e.g. ABCB1, SLCO1B1) and nuclear receptors (PXR and CAR). Genetic variation is detected through either targeted SNP genotyping using SNaPshot, PCR/RFLP, Taqman Assays or targeted sequencing of genes or sections of genes. The genes of interest are those that have been shown to be of pharmacogenomics relevance.

We also have a huge interest in evaluation the effects of variation in the genes that determine differential susceptibility to virus infection (e.g. tetherin/BST-2), IL-10 and genes coding for chemokines and chemokine receptors. These virus restriction genes are crucial in the responses that determine whether one gets infected or not.  Our group focusses on genetic variation that affects susceptibility to and response to treatment in conditions such as HIV/AIDS, diabetes, cancer, malaria and schizophrenia.  Most of the currently used therapeutic drugs used in treatment of the above conditions, are substrates of polymorphic enzymes, transporters and receptors. For example, efavirenz and nevirapine, used as part of the first line antiretroviral therapy (ART) regimens, are principally metabolised by CYP2B6 and to a lesser extent by CYP1A2, CYP2A6, CYP3A4 and CYP3A5, most pf which also participate in the metabolism antimalarial drugs. Variation in the gene (ABCB1) coding for the multidrug resistance protein, P-gp and the orphan receptors PXR and CAR is also thought to play an important role in the observed variability. Ultimately, the group is aiming at decoding the genetic component that is involved in all the processes mentioned above, in order to come up with suitable algorithms that can be used to tailor medication to the right patient at the right dose and at the right time.  Below are the four major focus areas for our group.

Recently the group won a grant from the National Research Foundation (NRF) of South Africa to evaluate the effects of indigenous herbal compounds on the expression and activities of drug metabolising enzymes. In the current setting of African populations, many patients, in addition to prescribed therapy, they also take herbal medicinal compounds. Thus, our group seeks to investigate the effects of concurrent herbal and prescription drug administration.

1)      HIV/AIDS Pharmacogenomics

  1. Role of genetic variation in genes coding for drug metabolising enzymes, transports and receptors for antiretroviral drugs
  2. Investigating genetic determinants of differential susceptibility to HIV-1 infection in prenatally exposed children and evaluation of effects on neurocognitive development

2)     Schizophrenia Pharmacogenomics:

Evaluating the effects of genetic variation in patients requiring co-treatment for schizophrenia and HIV/AIDS (interaction between antipsychotics and ARV drugs)

3)   Differential Gene Regulation

  1. Effects of chemotherapeutic drugs treatment on the expression of drug metabolising enzyme coding genes and its pharmacogenomics relevance
  2. The role of microRNA regulation of  genes with pharmacogenomics relevance (i.e. looking at contribution of variation at the level of microRNAs on drug response) enzymes

4)      Pharmacogenetics and Genetic susceptibility to Type II Diabetes Mellitus (T2DM);

  1. a.      Investigating the genetic correlates of dyslipidaemia among diabetic patients