David Gerhold is a genomic toxicologist and team lead in the Toxicology in the 21st Century (Tox21) program within NCATS’ Division of Preclinical Innovation, where he is developing in vitro methods to identify toxic compounds by introducing differentiating stem cell models and the gene expression technologies RNAseq and RASL-Seq. These new technologies support efforts to reach several goals:
- Identify potentially toxic chemicals in the environment through the Toxicology in the 21st Century consortium;
- Identify biomarkers of genetic susceptibility to tobacco; and
- Facilitate drug development through the Therapeutics for Rare and Neglected Diseases program.
Previously, Gerhold pioneered gene expression microarray technology at Merck Research Laboratories, applying this expertise to identify kidney injury biomarkers. He subsequently co-led the Kidney Biomarker Working Group within the Predictive Safety Testing Consortium, collaborating across the pharmaceutical industry to qualify seven biomarkers with the Food and Drug Administration and publishing the findings in 2010. Gerhold also worked as a liaison with clinical nephrologists initiating translational studies to improve nephrology standard of care.
Gerhold’s unifying vision is to develop a high-throughput, robust gene expression platform and core facility. NCATS researchers will use the RASL-Seq platform to gather thorough dose- and time-response data, as well as extensive reference data sets, to unlock the meaning behind these data. Such a platform can help show the toxic mechanisms of drugs and environmental contaminants alike.
Gerhold uses RASL-Seq to determine the toxic mechanisms by which environmental contaminants affect neurons, liver hepatocytes and other cell types. These studies demand adoption and production of improved cellular models for toxic responses and for diseases, such as models derived from immortalized cells and induced-pluripotent stem cells (iPSC). Gerhold also uses iPSC technology to generate “disease-in-a-dish” models. For example, both RASL-Seq and RNAseq help researchers understand the effects of tobacco components on vascular endothelial cells. By producing these cells using iPSC from smokers with and without vascular disease, Gerhold can determine whether some patients are genetically susceptible or resistant to the disease.