Brian Layden, MD
Chief and Associate Professor

The major focus of our research is to investigate pathways involved in the development of type 2 diabetes, gestational diabetes, and other related disorders. Through genetic models, our laboratory is investigating different genes and pathways involved in glucose regulation/metabolism. In addition to genetic mouse models, we complement these approaches with a large range of in vitro approaches including cell-based assays and studies investigating isolated protein functional activity. Current projects are listed below.

Project 1: We have helped identify two novel G-protein coupled receptors (GPCRs), free fatty acid receptor-2 and -3 (FFA2 and FFA3), that have a role in how pancreatic islets adapt by increasing insulin secretion and production (see Layden et al., 2010). We have helped determine their role in islet biology, indicating an important role for both these receptors in glucose homeostasis. Because they are expressed in other tissue besides pancreatic beta cells, including adipocytes and the GI tract, we are using both global and conditional mouse models to examine the role of these receptors in other tissues.  Moreover, the ligands for both these receptors are short chain fatty acids (SCFAs), and SCFAs are derived from gut microbial fermentation of difficult to digest food (such as fiber). Because of this, we are also investigating the role of SCFAs in islet biology, its relationship to the gut microbiota, and related aspects of metabolism.

Project 2: Recently, we helped discover a novel gene, HKDC1, involved in glucose regulation during pregnancy. We have now shown that HKDC1 encodes a fifth hexokinase, challenging the dogma in the field that only 4 hexokinases exist.  We are continuing our exploration of this novel genetic findings, through genetic mouse models, observing how this gene contributes to whole body glucose and energy homeostasis.

For these projects, funding exists through the NIH R01 DK104927 (PI: Layden), R01 DK111848 (co-I), and VA Merit 1I01BX00382 (PI: Layden).

Villa SR, Priyadarshini M, Fuller MH, Bhardwaj T, Brodsky MR, Angueira AR, Mosser RE, Carboneau BA, Tersey SA, Mancebo H, Gilchrist A, Mirmira RG, Gannon M, Layden BT. Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival. Sci Reports. 2016; 6:28159.

Ludvik AE, Pusec CM, Priyadarshini M, Angueira AR, Guo C, Lo A, Hershenhouse KS, Yang GY, Ding X, Reddy TE, Lowe WL Jr, Layden BT. HKDC1 is a novel hexokinase involved in whole body glucose utilization. Endocrinology 2016; 157:3452-61.

Guo C, Ludvik AE, Arlotto ME, Hayes MG, Armstrong LL, Scholtens DM, Brown CB, Newgard CB, Becker TB, Layden BT, Lowe WL, Reddy TE. Regulatory Variation Associated with Gestational Hyperglycemia Regulates Expression of the Novel Hexokinase HKDC1. Nature Communications. 2015; 6:6069.

Jose Cordoba-Chacon, PhD
Associate Professor of Medicine

Our lab is interested in the molecular mechanisms regulated by PPARg in hepatocytes of adult mice that favor lipid deposition and the onset of non-alcoholic fatty liver disease (NAFLD).  We use genetically modified mouse models and adeno-associated virus to alter the expression of hepatocyte-specific genes in adult mice. Our experimental mice are fed specials diets that induce NAFLD and non-alcoholic steatohepatitis (NASH) that is assessed in the lab with the use of quantitative PCR, western-blot, gas chromatography/mass spectrometry, colorimetric assays to determine levels of plasmatic endpoints, ELISA, etc. In addition, our lab studies the hepatic molecular mechanisms regulated by different conjugated linoleic acids isomers and how these dietary supplements could be used to efficiently regulate body composition and glucose homeostasis.

References: Wolf-Greenstein et al. J Endocrinol. 2017 232(1):107-121
Lab: CMWT 604
Office: CMWT 816
Phone: 312-355-3565

Rob Sargis,MD, PhD
Assistant Professor
Director, Physician-Scientist Training Program

Over the last several decades, diabetes rates have increased dramatically in the U.S. and across the globe.  The impact of this epidemic on both individual and societal health has been catastrophic.  Thus, understanding the factors that promote diabetes risk and developing approaches to reduce that risk are essential for improving human health.  A burgeoning body of scientific evidence now implicates exposure to environmental toxicants acting as endocrine-disrupting chemicals (EDCs) in the development of diabetes and its associated metabolic disorders (i.e. obesity, dyslipidemia, nonalcoholic fatty liver disease [NAFLD], and cardiovascular disease [CVD]).  Our laboratory is devoted to understanding the mechanisms by which various EDCs induce metabolic dysfunction using a wide array of cellular and animal model systems as well as studies in human populations.  The goal of these studies is to understand how environmental pollutants impair insulin secretion and action as well as disrupt other endocrine pathways to promote deterioration in metabolic health.  Work in the laboratory also seeks to understand the factors that potentiate or ameliorate EDC-induced metabolic dysfunction.  Relevant windows of exposure include adulthood, pregnancy, and in utero and early post-natal life.  A long-term goal of this work is to advance knowledge about the impact of environmental health on metabolic disease risk in order to foster development of environmental policies and regulations that can meaningfully reduce diabetes risk.  This includes advancing efforts to specifically address the contribution of environmental injustice to diabetes-related health disparities.

Lab Manager: Michael Landeche

Papasani V. Subbaiah, PhD
Professor of Medicine

A major focus of our lab at present is the potential role of dietary docosahexaenoic acid (DHA) in brain function and development of neurological diseases. DHA is a well known ant-inflammatory compound that is uniquely concentrated in the brain, and is essential for the development and function of the brain. There is a negative correlation between the consumption of DHA and the prevalence of Alzheimer’s disease. However, attempts to increase the brain DHA levels and improve memory with the currently available supplements such as fish oil, algal oi, and krill oil in the patients have failed. In contrast, we have recently demonstrated that the brain DHA levels can be nearly doubled in adult mice by using lysophosphatidylcholine (LPC) form of DHA, and significantly improve the memory. We are investigating whether this strategy would be beneficial in the treatment and prevention of various neurological diseases, including Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and depression.

Another area of research is the effect of conjugated linoleic acids (CLA) in the regulation of insulin function and obesity. CLA are commonly used as food supplements to control weight. The potential mechanism by which certain isomers of CLA affect insulin signaling and glucose metabolism are being investigated.

Team Members: Sugasini Dhavamani, PhD, Poorna CR Yalagala, PhD
Phone: 312-996-8212

Pengwen Xu, PhD
Assistant Professor

The long-term goal of my research is to delineate essential neural pathways for energy balance, glucose homeostasis, eating disorder and other related behavior. I hope my research will provide novel central targets for developing therapeutic strategies to combat obesity, diabetes and eating disorders. We use Cre-loxP strategy to generate unique mouse models with genes of interest (estrogen receptor α/β, aromatase, and androgen receptor) manipulated in specific brain regions or populations of neurons at the time of choice. These mouse models are supplemented with chemogenetic and optogenetic approaches to manipulate the activity of specific neural populations in a real-time manner. By using these models, we aim to establish the physiological relevance of specific neural pathways and identify novel neural circuits that are important for metabolism, feeding, and other related behaviors.

Phone: 312-355-4918

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