Matthews research interests are broad and span transgenic technologies applied to insects and associated parasites, genetic recombination, genetic diversity, population genetics, genomics, diagnostics, transmission cycles, epidemiology, ecology, vector incrimination, drug screening, and genetic diversity of Trypanasoma cruzi and also Leishmania.

Currently Matthews primary research drive is to develop the molecular tools to interrupt transmission of vector borne diseases by transgenic modification of insect vectors using new molecular tools (CRISPR-Cas9 gene drive).

  Matthews active research lines also encompass experimental models for visceral leishmania, hybrid cell lines, diagnostics and comparative genomics. He has coordinated field research in various Latin America countries and has extensive collaborations with overseas partners.  With collaborators he was the first to produce transgenic dual fluorescent hybrids of Leishmania donovani and has developed and formalised a typing scheme (SNP-MLST) for T. cruzi. With Michael Miles and others Matthew revealed the mechanism of genetic exchange in T. cruzi in a landmark Nature paper. Other work includes the resolution of ecological, vector and host associations of T. cruzi, development of an efficient drug screening assay, improved diagnostics and the application of next generation sequencing technologies to answer fundamental phyloepidemiological questions.