John VandeBerg, PhD

Research Focus

Dr. VandeBerg established the laboratory opossum as a unique research resource for a broad range of human diseases. Laboratory opossums are small marsupials, which are born at the developmental stage of a 6-week human embryo and weigh 60-150g as adults. The embryonic state at birth enables research that is not possible with other laboratory animals. The resource, which has a steady state of 1,200 animals comprising 15 genetic stocks and inbred strains, is used to model human diseases in Dr. VandeBerg’s laboratory and in the laboratories of collaborating scientists from around the world.

An ongoing research initiative uses the laboratory opossum as a model for Zika virus infection, immune response, transmission, and induction of pathologies. Unlike mice, laboratory opossums are permissive to Zika virus infections despite mounting a robust immune response against the virus. The virus persists long term in opossums and becomes widely disseminated to the major organs. Several severe pathologies have been observed in infected animals, including Zika congenital syndrome which was induced by the intra-cranial inoculation of newborn opossum embryos with Zika virus.

A new initiative in Dr. VandeBerg’s laboratory is the application of CRISPR-Cas9 gene editing to create knockout opossums for the purpose of investigating the function of genes that are of particular interest in the opossum model. This technology was successfully performed with opossums for the first time in 2021. Also in 2021, a collaboration with Dr. Satish Kumar developed the first induced pluripotent stem cell (iPSC) lines from this species, which will be used in stem cell therapy experiments to treat or prevent hypercholesterolemia, non-alcoholic fatty liver disease, and steatohepatitis in a susceptible strain.

Work is in progress toward knocking out Pten, which is a tumor suppressor gene. The Pten knockout animals are expected to be highly susceptible to cancer. They will be used to investigate the mechanisms by which aflatoxin, a mold in corn-based and some other food products, causes hepatocellular carcinoma, which has an extremely high incidence in the Rio Grande Valley.

Mutants of the Pten gene also are implicated in creating a high risk of autism spectrum disorder, as well as neurodevelopmental pathologies, during fetal development. Pten knockout embryos and fetuses will be treated with aflatoxin or placebo to investigate brain development and behavioral abnormalities that persist after the treated animals become juveniles. Currently, research in progress is focused on the neurodevelopmental pathologies induced aflatoxin and another environmental carcinogen, benzo[a]pyrene in wild-type embryos and fetuses.