Neuroscience
Cytotoxic Edema
We are conducting genetic screens for genes that modify cell swelling in astrocytes. Understanding the genetic basis of cytotoxic edema has implications for stroke, traumatic brain injury, and other neurological conditions.
Psychiatric Genetics
We run eQTL screens across cerebral organoids for mechanistic studies in autism and other psychiatric and neurodevelopmental disorders. These screens identify genetic variants that influence gene expression in developing brain tissue.
Preclinical Pharmacology
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.
Environmental Toxicology
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 Projects
- SBIR funded project: Using cerebral organoids to identify modifiers of developmental neurotoxicants
- SBIR funded project: Developing an improved aneuploidy assay using single cell RNAseq