Takahisa Nakamura, PhD

The worldwide prevalence of obesity has reached epidemic proportions. With it, a host of associated diseases, such as Type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH), have proliferated. The need for effective treatments of these metabolic diseases has never been more urgent. That is why my research seeks to develop new strategies to cure or prevent obesity-associated metabolic disorders.

I initially became interested in diabetes research after my father received a T2D diagnosis. My family history makes the search for new therapeutics very personal. But even beyond this, I have always felt that intellectual dissection of the labyrinthine mechanisms of metabolism was worth pursuing.

We know that low-grade, chronic inflammation is a hallmark of obesity. It promotes the development of metabolic diseases like T2D. However, the mechanisms by which obesity provokes aberrant inflammation are not clearly defined. My long-term research goal is to develop strategies that prevent and, ultimately, cure metabolic disorders by elucidating the molecular mechanisms of obesity-induced inflammatory conditions.

I am particularly interested in understanding the underlying causes of common and altered characteristics of RNA-RNA-binding protein (RNA-RBP) networks and how disruption of these networks induces the inflammation and metabolic dysregulation in the pathogenesis of obesity-associated metabolic disorders.

In obesity, we have noted that dynamic alterations in the modification and localization of RNAs appear to modulate RNA-RBP networks. This, in turn, activates pro-inflammatory RBPs, such as double-stranded RNA (dsRNA) dependent protein kinase (PKR), and RNA silencing machinery. The alterations we observed, which were documented in research journals such as Cell, Cell Reports and Nature Communications, seem to contribute to the induction of aberrant inflammation and the development of metabolic diseases.

I also investigate the role of extracellular vesicles (EVs) and extracellular RNA (exRNA) in the regulation of inflammation in obesity. EVs, including nanosized exosomes (30 – 150 nm in diameter), have emerged as important transducers of intracellular communication. Analysis of EV cargoes shows that exRNA, such as microRNA found within EVs, can interact with immune cells and induce inflammation.

Having studied the sophisticated regulation of systemic glucose, lipid and energy metabolism for most of my academic career, I hope my research efforts will help deepen our scientific knowledge of the complex interplay between these factors. One day, I hope my work will result in a better quality of life for patients with diabetes and other metabolic diseases.

I began working with the team at Cincinnati Children’s in 2013. Beyond my work here, I also work as an associate professor in the Department of Metabolic Bioregulation, Institute of Development, Again and Cancer, Tohoku University, Sendai, Japan.