Welcome to the Krishnan Lab. We are part of the Genes and Human Disease program at the Oklahoma Medical Research Foundation, Oklahoma City.
Lab overview
Millions of people worldwide are affected by metabolic disorders including diabetes, obesity and the associated cardiovascular diseases. In an effort to find novel methods for intervention and new therapeutic targets, we turned to the nature for answers. The concept of looking for naturally available solutions isn’t new. Airplanes, velcro, wetsuit, etc. are all inspired by nature. Likewise, there are organisms that can give us insights into metabolic disorders too.
Organisms such as hibernating mammals, migratory birds, and our favorite – the fat cavefish Astyanax mexicanus have all adapted to store excess fat in their bodies so they can survive very long periods of low nutrient supplies. More than 150,000 years ago, the river-dwelling Astyanax mexicanus – the surface fish – got swept into and trapped in the lightless, nutrient-scarce caves in the Sierra del Abra region of Mexico where they faced seasonal limitations in food availability, leading to extended periods of starvation. Astonishingly however, they successfully survived in these habitats thanks to the adaptations they evolved. They evolved to binge eat whenever food is available, maintain high blood glucose levels, accumulate excess body fat, and develop fatty liver – all signs of metabolic disease –albeit without any negative effects of toxicity or inflammation. We simply asked how they do so and if we can study them to better understand human metabolic diseases such as diabetes and obesity. We use modern molecular, genomic and metabolomic approaches tools to study these processes in greater detail as well as discover underlying causal genes.
Our studies shed light on the evolutionary forces shaping cavefish physiology and also draw a bridge to human health. Our mission is to extend our findings beyond the lab to pave the way for innovative approaches in addressing metabolic disorders in humans.