Biomedical subjects

Greg Collier

Publications and source records attributed to Greg Collier.

3 recordsLinked to original sources

PubMed2003

Beacon interacts with cdc2/cdc28-like kinases.

Previously we found elevated beacon gene expression in the hypothalamus of obese Psammomys obesus. Beacon administration into the lateral ventricle of P. obesus stimulated food intake and body weight gain. In the current study we used yeast two-hybrid technology to screen for proteins in the human brain that interact with beacon. CLK4, an isoform of cdc2/cdc28-like kinase family of proteins, was identified as a strong interacting partner for beacon. Using active recombinant proteins and a surface plasmon resonance based detection technique, we demonstrated that the three members of this subfamily of kinases (CLK1, 2, and 4) all interact with beacon. Based on the known sequence and functional properties of beacon and CLKs, we speculate that beacon could either modulate the function of key regulatory molecules such as PTP1B or control the expression patterns of specific genes involved in the central regulation of energy metabolism.

Brain↗

PubMed2002

Familial resemblance for plasma leptin: sample homogeneity across adiposity and ethnic groups.

OBJECTIVE: Previous studies show a wide range in the percentage of variance in leptin levels attributable to genetic factors. These studies differ markedly with respect to ethnicity, study design, and statistical methodology. Therefore, the purpose of this study was to investigate heterogeneity hypotheses across ethnic groups and by adiposity level, using the same statistical methods. RESEARCH METHODS AND PROCEDURES: Samples included black vs. white (HERITAGE Family Study) and random vs. obese (Québec Family Study) individuals from 432 families (1432 individuals). Heritability for leptin, alternatively adjusted for age and sex and then for age, sex, and adiposity was estimated with the use of familial correlations. Heterogeneity in the magnitude of the familial resemblance between samples and the effect of adjusting for adiposity was explored. RESULTS: Heritability did not vary across samples stratified by adiposity level or ethnic group or across adjustment schemes. Maximal heritability, the percentage of additive phenotypic variability due to all familial sources, was 32%. DISCUSSION: Whereas leptin and adiposity were highly correlated within individuals, removing the effects of adiposity did not significantly alter the magnitude of the familial component for leptin. Moreover, this effect did not vary as a function of ethnicity (black vs. white) or adiposity level. Thus, no evidence for heterogeneity was detected. However, a comparison among previous studies raises questions concerning possible genetic heterogeneity in other ethnic groups in which complex interactions among leptin, adiposity, and diabetes status may be important.

Adipose Tissue↗

PubMed2002

New approaches to gene discovery with animal models of obesity and diabetes.

DNA-based approaches to the discovery of genes contributing to the development of type 2 diabetes have not been very successful despite substantial investments of time and money. The multiple gene-gene and gene-environment interactions that influence the development of type 2 diabetes mean that DNA approaches are not the ideal tool for defining the etiology of this complex disease. Gene expression-based technologies may prove to be a more rewarding strategy to identify diabetes candidate genes. There are a number of RNA-based technologies available to identify genes that are differentially expressed in various tissues in type 2 diabetes. These include differential display polymerase chain reaction (ddPCR), suppression subtractive hybridization (SSH), and cDNA microarrays. The power of new technologies to detect differential gene expression is ideally suited to studies utilizing appropriate animal models of human disease. We have shown that the gene expression approach, in combination with an excellent animal model such as the Israeli sand rat (Psammomys obesus), can provide novel genes and pathways that may be important in the disease process and provide novel therapeutic approaches. This paper will describe a new gene discovery, beacon, a novel gene linked with energy intake. As the functional characterization of novel genes discovered in our laboratory using this approach continues, it is anticipated that we will soon be able to compile a definitive list of genes that are important in the development of obesity and type 2 diabetes.

Animals↗