The Nault lab's mission is to integrate innovative, emerging, and established methodologies to advance our comprehension of the spatially resolved and cell-specific impacts of chemicals and drugs during the development and progression of liver disease. Through leveraging of innovative experimental techniques and computational approaches, our objective is to gain mechanistic insights into the effects of genetic and environmental factors in the development and progression of disease at an unprecedented level of detail in hopes to support the development of effective personalized strategies to protect human health.
CURRENT RESEARCH AREAS:
ROLE OF SPATIAL CELLULAR HETEROGENEITY IN ZONE-BIASED STEATOTIC LIVER DISEASE
The liver's structure is highly organized into functional units called lobules, which display clear functional zones of based on physiological gradients. Blood rich in oxygen and nutrients enters the liver through the portal vein and eventually drains into the central vein. This creates gradients in oxygen and nutrients across the liver, and the liver's metabolic activities are adapted to these gradients.
In liver diseases, damage or dysfunction often shows distinct patterns depending on the underlying cause. For example, the buildup of fat in the liver (a condition known as steatosis) can occur in specific areas—either near the portal vein (zone 1) or near the central vein (zone 3). However, the exact reasons why fat accumulates in one area or the other are still unclear.
Our team is using advanced spatial transcriptomic technologies to study how differences in liver cell function, depending on their location, contribute to liver disease. By mapping these differences, we aim to better understand the mechanisms behind conditions like steatosis and develop more targeted treatments.
IMPORTANCE OF GENETIC AND ENVIRONMENTAL FACTORS IN SPATIAL CELLULAR HETEROGENEITY
Both genetic makeup and environmental factors are key in shaping our health and how diseases develop. Thanks to advances in technology, scientists now have a better understanding of how genetic differences in people influence the onset and progression of diseases, as well as their response to treatments. These differences often show up in specific types of cells and may even vary depending on where those cells are located in the body. Our team is using models that reflect genetic diversity to explore how variations in the population could affect the risk and progression of metabolic diseases and responses to harmful substances.
MECHANISTIC INVESTIGATION OF TOXICANT INDUCED TOXICITY USING ARTIFICIAL INTELLIGENCE