Blackburn Research Projects
CURRENT RESEARCH PROJECTS – A BRIEF OUTLINE BELOW
Mechanisms of disease: The Blackburn group is actively involved in interdisciplinary research to describe molecular factors driving TB transmission, utilizing state-of-the-art mass spectrometry to characterize molecular phenotypes associated with successful transmission of Mycobacterium tuberculosis bacilli, as well as with establishment of latent TB infections. We also carry out proteomics research on patient-derived clinical samples to unravel underlying molecular mechanisms in the emergent HIV-associated TB immune reconstitution inflammatory syndrome (TB-IRIS) - a life-threatening syndrome that afflicts ca. 20% of patients who are dual infected with HIV and TB and on front line anti-TB and antiretroviral therapies.
Diagnostics: The tuberculosis (TB) field is in desperate need of new biomarkers in a number of areas, including markers of disease, of susceptibility to disease and of cure after therapy. In collaboration with leading clinical groups in Cape Town, the Blackburn group carries out mass-spec-based differential proteomic and lipidomic research to identify and validate novel urinary biomarkers of TB disease status.
HIV-associated neurocognitive disorders (HAND)
Mechanisms of disease: In South Africa, up to ~45% of HIV patients on long term antiretroviral therapy develop neurocognitive impairments. Neurons are not themselves thought to be susceptible to HIV infection so the molecular basis of HAND remains uncertain. A number of etiological agents seem plausible, including: HIV proteins such as Tat; CNS-penetrating anti-retroviral drugs; & inflammatory cytokines secreted by HIV-infected monocytes that have pemeated the blood-brain barrier. In collaboration with leading clinical groups in Cape Town and with Smith stem cell group in Cambridge, UK, the Blackburn group is building in vitro models of HAND using non-transformed human neural stem cells. We then use mass spectrometry-based proteomic analysis coupled with cell biology-based functional readouts to begin to unravel the possible molecular mechanisms that drive development of HAND, as well as to identify possible targets for selective therapeutic intervention.
Diagnostics: Colorectal cancer remains one of the most difficult cancers to accurately diagnose and stage, largely due to the strongly invasive nature of current tests. The Blackburn group carries out both genomic and protein microarray-based studies on a family of candidate genes/proteins identified through bioinformatics methods, with the aim of identifying patterns of variation in the expression of this specific set of genes and/or proteins that might correlate with disease status and prognosis. Our work is based on access to well characterised tissue and blood samples from a cohort of colorectal cancer patients, rather than on immortalised cancer cell lines, and our goal is to identify a 'biosignature' that can provide both diagnostic and prognostic information in the pre-symptomatic stages of disease.
Effect of Polymorphic Variation on P450-Mediated Drug Metabolism
Precision medicine: Genetic variation between patients lies at the heart of the observation that the efficacy of drugs varies widely between individual patients and also directly affects susceptibility to adverse drug-drug reactions. Currently however no accurate, quantitative and genuine comparative methods exist for assessing the effect of single nucleotide polymorphisms on the activity of P450 enzymes, the enzymes typically responsible for the first steps in drug metabolism. The Blackburn group is therefore developing and validating novel protein function microarrays - P450 biochips – as well as novel computational approaches that we can use, amongst others, to assess the effect of genetic variation on the primary metabolism of clinically-prescribed drugs, as well as on propensity to adverse drug reactions
Next generation point of care diagnostic devices
Diagnostics: The Blackburn group has active research programs aimed at designing novel point of care diagnostic devices for use in low resource settings in the developing world. Our current programs are focused in particular on the design and validation of surface enhanced Raman scattering spectroscopy-based biosensors for diagnostic applications.