Translation and Systems Biology: Mathematical and computational modeling at the frontier of biomedical research

Job Candidate Talk
Thursday, February 7, 2019 - 10:00am for 1 hour (actually 50 minutes)
Skiles 006
Gesham Magombedze – Baylor Institute for Immunology Research – gesham.magombedze@bswhealth.org
Howie Weiss

A major challenge in clinical and biomedical research is on translating in-vitro and in- vivo model findings to humans. Translation success rate of all new compounds going through different clinical trial phases is generally about 10%. (i) This field is challenged by a lack of robust methods that can be used to translate model findings to humans (or interpret preclinical finds to accurately design successful patient regimens), hence providing a platform to evaluate a plethora of agents before they are channeled in clinical trials. Using set theory principles of mapping morphisms, we recently developed a novel translational framework that can faithfully map experimental results to clinical patient results. This talk will demonstrate how this method was used to predict outcomes of anti-TB drug clinical trials. (ii) Translation failure is deeply rooted in the dissimilarities between humans and experimental models used; wide pathogen isolates variation, patient population genetic diversities and geographic heterogeneities. In TB, bacteria phenotypic heterogeneity shapes differential antibiotic susceptibility patterns in patients. This talk will also demonstrate the application of dynamical systems in Systems Biology to model (a) gene regulatory networks and how gene programs influence Mycobacterium tuberculosis bacteria metabolic/phenotypic plasticity. (b) And then illustrate how different bacteria phenotypic subpopulations influence treatment outcomes and the translation of preclinical TB therapeutic regimens. In general, this talk will strongly showcase how mathematical modeling can be used to critically analyze experimental and patient data.