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Deena J. Small, Ph.D.EDUCATION:
Ph.D., University of Maine, Orono; 1998
B.S., University of Maine. Orono; 1992
POST-DOCTORAL EXPERIENCE:
Maine Medical Center Research Institute
Center for Molecular Medicine
Scarborough, Maine
1998-2003
COURSES TAUGHT:
- Clinical Chemistry (UNH)
- Cell and Molecular Biology (University of New England, Biddeford, Me)
- Cell and Molecular Biology (University of Maine, Augusta, Me.)
GENERAL AREA OF INTEREST AND/OR SPECIALTY:
- Tumor Biology
- Adipogenesis/ Obesity/ Type 2 Diabetes
CURRENT RESEARCH AND/OR PROFESSIONAL ACTIVITIES:
Notch receptors and their ligands are evolutionarily conserved, transmembrane polypeptides that regulate cell fate determination events in virtually all cell types examined to date. Notch's ability to direct a cell to proliferate, differentiate or grow is dependent on the cell type and the activity of other signaling pathways present within the cell. For example, activation of Notch prevents myoblasts from undergoing myogenesis, but is required for preadipocytes to differentiate into mature fat cells. However, the molecular mechanisms by which the Notch signaling pathway directs these decisions through its communication with other signaling pathways is little understood. Since aberrant Notch signaling is associated with the development of cancer, I have been interested in studying Notch's role in regulating cellular growth. In particular, I am trying to identify the mechanism by which Notch communicates with the FGFR pathway as I have found that antagonistic interactions between these two pathways pre vents abnormal growth in the NIH 3T3 cell.
In addition, to studying Notch's role in tumorigensis, I have recently become interested in examining the function of Notch as a regulator of adipogenesis. White Adipose tissue (WAT) is a richly vascularized, specialized form of connective tissue comprised primarily of fat-storing adipocytes. Although WAT was previously considered to simply be a fat depository that passively participated in metabolic homeostasis by storing or releasing lipid in response to hormonal stimuli, WAT is now recognized as a dynamic endocrine organ that actively regulates many biological processes. Indeed, adipocytes secrete factors that not only control energy balance and insulin sensitivity in WAT and other tissues including liver, skeletal muscle and pancreas, but also mediate immunological responses and maintain vascular health. Pathological conditions characterized by an excess (obesity) or paucity (lipoatrophy) of WAT is a major risk factor for metabolic syndrome and type2 Diabetes (NIDDM) as well as cardiovascular disease, indicating that maintenance of WAT within a normal physiological range is important for continued physical health throughout an organism's life history.
Intense research over the last decade has led to the identification of the signal transduction pathways controlling adipocyte differentiation and function. These studies led to the discovery that transcription factors belonging to the CAAT/Enhancer Binding Protein (C/EBP) and Peroxisome Proliferation -Activator Receptor (PPAR) families are key players controlling adipogenesis and adipocyte gene transcription. Activation of PPARg with synthetic ligands such as Thiazolidinediones have profound effects on lipid and lipoprotein metabolism as well as insulin sensitivity and are therefore used as therapeutic agents in the treatment of obesity, metabolic syndrome and NIDDM. Although Notch1 was identified as an important regulator of adipocyte differentiation, further reports regarding Notch's role in adipogenesis , either in vitro or in vivo have not been forthcoming. Furthermore, the mechanism by which Notch influences expression and/or activity of C/EBPa or PPARg is still unknown. Given that both c/EBPa or PPARg -regulated transcriptional events are not only important for adipocyte differentiation and function, but are also involved in mediating metabolic responses in skeletal muscle, liver and pancreas, elucidation of the relationship between a ubiquitous signaling pathway like Notch and the activity of these factors will further our understanding of disease states attributed to aberrant metabolic function.
REPRESENTATIVE PUBLICATIONS:
Small D., Kovalenko D., Soldi R., Mandinova A., Kolev V., Trifonova R., Bagala C., Kacer D., Battelli C., Liaw L., Prudovsky I., Maciag T. Notch Activation Suppresses FGF-Dependent Cellular Transformation. J. Biol. Chem. 2003; In Press.
Small D., Kovalenko D., Kacer D., Liaw L., Landriscina M., Di Serio C., Prudovsky I., Maciag, T. Soluble Jagged 1 Represses the Function of Its Transmembrane Form to Induce the Formation of the Src-dependent Chord-like Phenotype. J. Biol. Chem. 2001; 276:32022-32030.
Lindner V., Booth C., Prudovsky I., Small D., Maciag T., Liaw L., Members of the Jagged/Notch Gene Families are Expressed in Injured Arteries and Regulate Cell Phenotype via Alterations in Cell-matrix and Cell-cell Interactions. Am. J. Pathol., 2001; 159:875-883.
Wong MKK., Prudovsky I., Vary C., Booth C., Liaw L., Mousa S., Small D., Maciag, T. A Non-Transmembrane Form of Jagged-1 Regulates the Formation of Matrix-dependent Chord-like Structures. Biochemical and Biophysical Research Communications. 2000; 268:853-859.
Prudovsky I., Landriscina M., Soldi R., Bellum S., Small D., Andreeva V., Maciag T., FGF Reporter Gene Chimeras to Study Nuclear Translocation and Non-Classical Exocytosis. Meth.Enzymol., 2000; 327:369-382.
