Discovering the etiology of complex traits with
in vitro genetics.
Variable drug response.
Population based environmental toxicology.
What We Do
Predictive Biology brings together genetics, stem cell biology, organoids and single cell technologies to characterize the molecular basis of disease phenotypes and drug response.
We use our in vitro genetics platform to elucidate molecular mechanisms of action and to find and validate novel drug targets.
Current Research Programs
Cytotoxic Edema: a genetic screen for genes that modify cell swelling in astrocytes.
Psychiatric Genetics: an eQTL screen across cerebral organoids for mechanistic studies in autism and other psychiatric and neurodevelopmental disorders.
Preclinical studies usually test compound action in a small number of cell lines and animal models. Response in genetically diverse backgrounds is often considered only in clinical studies, where there is limited statistical power and no opportunity to modify the molecule. We believe that drug action across genetic diversity should be evaluated in preclinical studies when the molecule has druglike properties but remains available for chemical modification. At this stage, there is little if any data from in vivo studies.
Impact on Discovery: In vitro genetic screens can be used to identify causal mediators of drug response, and genetically validated targets can double the likelihood of a successful drug discovery program.
Impact on Prioritization: Chemically related preclinical compounds often exhibit different pharmacological properties. A better understanding of the mechanism of action would help prioritize them for clinical studies.
It is widely accepted that genetics plays a major role in susceptibility to toxicants but how genetics shapes toxic response is poorly understood. For environmental health science, finding the genes that modulate susceptibility will drive mechanistic understanding of toxicity, which in turn will drive development of more predictive toxicity assays. For public safety, genetic stratification of susceptibility can aid exposure limit setting by regulatory bodies.
For drug discovery, where safety issues account for half of drug failures in clinical trials, identifying genes and pathways that modulate adverse drug response can lead to better engineered molecules that reduce safety risk. For preventive medicine, identifying those at greater risk from toxicant exposure can improve allocation of limited healthcare resources.
Current toxicology research projects include an SBIR funded project to use cerebral organoids to identify modifiers of developmental neurotoxicants, and an SBIR funded project to develop an improved aneuploidy assay using single cell RNAseq.