Home > Faculty > Dr. Nevis L. Fregien

 

 

Nevis L. Fregien, Ph.D.

Associate Professor of Cell Biology & Anatomy
Telephone: (305)243-6941
FAX: (305)243-4431
nevis@miami.edu

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Curriculum Vitae

B.S., Biochemistry, University of California at Davis 1976
Ph.D., Biochemistry & Biophysics, University of Hawaii at Manoa, 1981
Postdoctoral Fellow, California Institute of Technology, 1981 - 1986
Assistant Professor, University of Miami, 1986 - 1993
Associate Professor, University of Miami, 1993 - present

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Research Interests

Research in my laboratory focuses on investigating the molecular regulation of cellular commitment and differentiation and the reversal loss of differentiation. The studies are designed to lay the foundations for the discovery of new therapies to treat and cure diseases. We have used several systems to study this fundamental biological problem of how cell fate is decided both in the embryo and during renewal of cells in organs and tissues. These processes are central in the development of many diseases.

For example, the change that occurs during the progression of cancer cells into lethal, invasive metastatic cells resembles a dedifferentiation process and learning how the normal differentiated phenotype is maintained is of central importance to understanding cancer progression. The most life threatening aspect of cancer is its ability to metastasize or move to different locations in the body. One of the most common features of metastatic tumor cells is the abnormal expression of cell surface oligosaccharide molecules. The expression of these molecules gives malignant cells metastatic capacity by changing the cellular adhesive properties and promotes their relocation from the primary tumor site to a secondary site or by protecting the tumor cell from recognition and degradation by the immune system. The genetic regulation of oligosaccharide synthesis is accomplished by controlling the expression of the enzymes, known as glycosyltransferases that make them. Therefore, we are studying the transcriptional regulation of two glycosyltransferases that are critical for this process, one for N-linked oligosaccharides and another for O-linked oligosaccharides. We have cloned the promoters and our analysis show that these genes contain multiple promoters. Furthermore, transcription from at lease some of these promoters can be induced by oncogenes. We are currently attempting to develop methods to reduce the expression of these genes.

Another example we are currently studying is the mechanism of ciliogenesis by which ciliated cells are formed in the airway and how this ciliated phenotype is maintained. Ciliogenesis is partially controlled by the transcriptional regulator Foxj1 that is a member of the forkhead gene family. Expression of this gene is tightly controlled, precedes the expression of the ciliated phenotype, and is required for ciliogenesis. We are currently studying the role of apical junctions in regulating Foxj1 expression.


Diagram of the Foxj1 promoter fragment with intron and after deletion.

 

 

 

 


Tight junction formation during airway epithelia development

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Selected Publications

Schmid A, Bai G, Schmid N, Zaccolo M, Ostrowski LE, Conner GE, Fregien N, Salathe M. (2006) Real-time analysis of cAMP-mediated regulation of ciliary motility in single primary human airway epithelial cells. J Cell Sci Sep 19 [Epub ahead of print]

Fregien NL, White LA, Bunge MB, Wood PM. (2005) Forskolin increases neuregulin receptors in human Schwann cells without increasing receptor mRNA. Glia. 49:24-35.

Falkenberg VR, Alvarez K, Roman C, Fregien N. (2003) Multiple transcription initiation and alternative splicing in the 5' untranslated region of the core 2 beta1-6 N-acetylglucosaminyltransferase I gene. Glycobiology 13:411-8.

Levine J, Buchman CA, Fregien N. (2003) Influenza A virus infection of human Schwann cells in vitro. Acta Otolaryngol 123:41-5.

Alverez K, Haswell C, St Clair M, Perng GS, Shorebah M, Pierce M, Fregien N. (2002) Sequences of the mouse N-acetylglucosaminyltransferase V (Mgat5) mRNA and an mRNA expressed by an Mgat5-deficient cell line. Glycobiology 12:389-94.

Buchman, C.A. and Fregien, N. Influenza A virus infection of human middle ear cells in vitro. 2000. Laryngoscope 110:1739-1744.

Carraway, K.L III, Rossi, E.A., Komatsu, M., Price-Shiavi, S.A., Huang, D., Guy, P.M., Carvajal, M.E., Fregien, N., Carothers Carraway, C.A. and Carraway, K.L. 1999. An intramembrane modulator of the ErB2 receptor tyrosine kinase that potentiates neuregulin signaling. J. Biol. Chem. 274(9):5263-5266.

Buchman, C.A. and Fregien, N. 1999. Primary middle ear epithelial cell culture and gene transfer. Proceedings of the Seventh International Symposium on Recent Advances in Otitis Media. Ft. Lauderdale, FL.

Price, S. Carraway C.A.C., Fregien, N. and Carraway, K.L. 1998. Post-transcriptional regulation of a milk membrane protein, the sialomucin complex (ASGP-1/ASGP-2, rat Muc4), by TGF 1. J. Biol. Chem. 273(52):35228-37, 1998.

Chen, L., Buckhaults, P., Fregien, N. and Pierce, M. 1998 The her-2/neu oncogene stimulates the transcription of N-acetylglucosaminyltransferase V and expression of its cell surface oligosaccharide products. Oncogene, 17(16):2087-2093.

McNeer, R.R., Carraway, C.A.C., Fregien, N.L. and Carraway, K.L. 1998. Characterization and Steroid Hormone Control of Sialomucin Complex in Rat Uterus: Implications for Uterine Receptivity.
J. Cell. Phys., 176:110-119.

McNeer, R.M., Huang, D., Fregien, N. And Carraway, K.L. 1998. Sialomucin Complex in the rat respiratory tract: a model for its role in epithelial protection. Biochem. J. 330:737-744.

Masanobu, K., Carraway, C.A.C., Fregien, N. And Carraway, K.L. 1997. Reversible disruption of cell-matrix and cell-cell interactions by overexpression of sialomucin complex. J. Biol. Chem. 272:52:33245-33254.

 

View published research articles by Dr. Fregien in the National Library of Medicine

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