Lifestyle-related diseases are rising in the 21st century and will be a global issue if strategies are not developed to mitigate them. The major contributors are diet and the environment. The overall goal of the Bhandari Lab's research program is to understand how gene-environment interactions lead to adverse health outcomes, including diseases.

To understand this broad question, we are considering chemicals and nutrition to which humans and other non-human vertebrate organisms are exposed as environment, epigenetic mechanisms as drivers, and altered health outcomes, mainly early embryonic development and later life reproductive and metabolic health, as phenotypic traits. We have found that environmental stress, including nutritional, occurring during sensitive life history stages can cause adult-onset or transgenerational health effects at the reproductive, metabolic, and behavioral levels. We are trying to understand how somatic cells transmit health information from embryonic stages to adulthood and how germline cells memorize, process, maintain mitotically/meiotically, and transmit stressor-induced effects from one generation to another via germline transmission.

We use comparative, molecular, cellular, and bioinformatics approaches and in vitro 3D human cell co-culture and in vivo animal models (fish and rodents) in research. We use advanced research tools, including next-generation genomic and epigenomic analysis, transgenesis, and CRISPR-Cas9/dCas9-mediated genome/epigenome editing, to understand mechanisms underlying environmentally induced altered health conditions and inheritance of health effects in the same and subsequent generations.

We have characterized epigenetic memories established by select environmental stressors in somatic and germline cells and are targeting them with CRISPR epigenome editing tools to delineate their role in developing latent and transgenerational reproductive and metabolic health effects. Additionally, we are developing strategies to mitigate environmentally induced epigenetically mediated health effects so that the pathway to phenotypic defects can be diverted to normal morphogenetic pathways before the onset of pathogenesis.

Overall, we strive to understand the developmental origins of adult-onset and transgenerational phenotypic alterations and develop strategies to protect human and organismal health.