“We intend to understand at the molecular level the communication between organ systems and how this is affected in common metabolic pathologies.”

The rising prevalence of type 2 diabetes (T2D) constitutes a major health problem that strongly correlates with an elevated incidence of obesity. It is estimated that almost 500 million people will suffer from this disease worldwide in 2030.

The crosstalk between tissues that regulate metabolic homeostasis in response to environmental and nutritional demands is impaired in T2D patients.

The liver has a pivotal role in controlling the metabolism of carbohydrates and lipids and the secretion of bioactive molecules, including pro- and anti-inflammatory hepatokines that are involved in multi-organ crosstalk. Characterisation of small molecules and hepatokines involved in this communication is critical to understanding the molecular mechanisms that lead to insulin resistance, the decline in b-cell function, inflammation and cardiovascular complications associated with T2D and obesity.

We will use both computational and experimental approaches to identify the molecules involved in the crosstalk between hepatocytes, the main form of liver cell, and other cellular populations such as adipocytes, beta-cells, immune cells or neurons, in health and disease. The characterisation of these molecules will provide valuable information about hepatic and systemic metabolic homeostasis.

Our long-term goal is to identify and characterise new metabolic regulators relevant for human metabolic pathologies such as T2D and obesity to uncover novel targets for the design of improved diagnostic and therapeutic strategies.

Santiago group page iamge

Diet-induced obesity is associated with metabolic changes in the liver. Images show lipid droplets (green) and nuclei (blue) in primary hepatocytes (left), the main form of liver cell, and hematoxylin/eosin staining of liver sections (right) from mice fed a control diet (CD) or a high-fat diet (HFD) for 16 weeks

Selected Publications

Vernia S, Morel C, Madara J, Cavanagh-Kyros J, Barrett T, Chase K, Kennedy N, Jung DY, Kim J, Aronin N, Flavell R, Lowell BB and Davis RJ. “Excitatory transmission onto AgRP neurons is regulated by cJun NH2-terminal kinase 3 in response to metabolic stress”. eLife, 2016; 5:e10031

Vernia S, Cavanagh-Kyros J, Barrett T, Tournier C and Davis RJ. “Fibroblast growth factor 21 mediates glycemic regulation by hepatic JNK””. Cell Reports. 2016. 14, 1-8, March 15, 2016.

Thornton TM, Delgado P, Chen L, Salas B, Krementsov D, Fernandez M, Vernia S, Davis RJ, Heimann R, Teuscher C, Krangel MS, Ramiro AR, Rincón M.” Inactivation of nuclear GSK3β by Ser(389) phosphorylation promotes lymphocyte fitness during DNA double-strand break response”. Nat Commun. 2016 Jan 29;7:10553.

Vernia S, Cavanagh-Kyros J, Garcia-Haro L, Sabio G, Barrett T, Jung DY, Kim JK, Xu J, Shulha HP, Garber M, Gao G, Davis RJ. “The PPARα-FGF21 Hormone Axis Contributes to Metabolic Regulation by the Hepatic JNK Signaling Pathway”. Cell Metabolism 20, 1-14, Sept 2, 2014.

Vernia S, Cavanagh-Kyros J, Barrett T, Jung DY, Kim JK, Davis RJ. “Diet-induced obesity mediated by the JNK/DIO2 signal transduction pathway”. Genes and Development. 2013 Nov 1;27(21):2345-55.