ASSOCIATED PROFESSOR K. SHIRES

Associate Professor Karen Shires, is a joint staff Senior Medical Scientist and Senior Lecturer at UCT medical school and NHLS Cape Town. After obtaining various scientific degrees in the pathology disciplines of Microbiology, Biochemistry and Chemical Pathology, Dr Shires joined the NHLS, Division of Haematology in 2006.

She is in charge of the research and development of the molecular section, which has allowed her to develop novel diagnostic and prognostic approaches in her research lab, and translate these directly to the molecular NHLS service at Groote Schuur Hospital. Quality and reliable testing platforms that make use of efficient workflow systems guide her guidelines in supplying clinically relevant molecular testing solutions for the local Haematopathology discipline. Her research focus is on the development of novel molecular tools to diagnose and monitor minimal residual disease in Multiple Myeloma and myeloid malignancies. She is a passionate teacher and leads the molecular haematology teaching and training for registrar with an online lecture series, molecular tutorials and practical workshops. She also provides ongoing training and teaching, private clinicians, technologists and other interested scientists. Dr Karen Shires continues to serve as a national examiner for both the Haematology and Molecular Biology national intern medical scientists training programs for the HPCSA, is also a member of the HPCSA medical scientist task team (UCT/GSH-NHLS representative) and is also an external examiner for national Hons, MMed, MSc and PhD theses.

Cancer/Testis antigen expression in Multiple Myeloma
Cancer/Testis antigens (CTAs) are a group of highly immunogenic proteins that show testis-restricted expression in normal tissue, but high expression in many different cancer types. In recent years CTA expression in Multiple Myeloma (MM) has been explored, with the discovery that some of these antigens are commonly expressed. Their expression has been linked with advanced disease and poor overall survival. Although they are being actively investigated for immunotherapy uses, little is known about their role in MM pathogenesis. In an attempt to understand both their role in disease and as a potential prognostic and monitoring tool, the research group of Dr Shires is actively investigating the expression of a panel of CTAs in MM patients at diagnosis and during therapy. They have already reported a cascade like expression pattern linked to worsening disease features and showed that MAGEC1 expression is expressed in a stem cell component of the disease which may represent the progenitor malignant cell. Current studies involve how various chemotherapy treatments affect this progenitor cell and how monitoring of transplant patients using CTA expression can improve overall survival by predicting relapses at an early time frames.

Diagnosis, prognosis and monitoring of myeloid malignancies
Providing first-world diagnostic tests in state hospital facilities is an important goal of the NHLS, however, costs in our local setting are a significant limiting factor.  The Molecular Haematology unit run by Dr Shires aims to provide the best possible molecular service to help diagnose, prognosticate and monitor disease in patients with myeloid malignancies, despite these constraints. This includes developing novel strategies to test for multiple mutations on single platforms, establishing the relevance of particular mutations in local populations and identifying novel disease-causing mutations in our local population groups.

The prevalence of JAK/CALR/MPL mutations in our local populations are being researched as it appears that the rate of these mutations in our MPN patient population is not the same as reported in Europe and the US. This leads the way to study alternative disease mechanisms in our African population. We are also currently developing novel assays to detect multiple prognostic indicators for patients with AML, in line with the WHO recommendations.