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Naohiro Terada , M.D., Ph.D. Associate Professor
	Dept. of Pathology, Immunology and Laboratory Medicine  University of Florida College of Medicine  P.O. Box 100275  Gainesville, FL 32610-0275  Office Location and Express Mail address:  Dept. of Pathology, Immunology and Laboratory Medicine  University of Florida College of Medicine  M652 1600 SW Archer Rd Gainesville, FL 32610-0275 Office: (352) 392-2696 Fax: (352) 392-6249 Senior Secretary: Mandy Nevills (352) 392-2886  Email: terada@pathology.ufl.edu
Currently Involved In: Stem Cell Biology & Regenerative Medicine Lab Manager: Amy Meacham Instructor (Assistant Scientist): Charlie Hamazaki IDP Predoctoral Students: Sarah Kehoe, Jeff Brower, Katherine Hankowski Undergraduate Volunteers: Josh Rogozinski, Rebecca Kirschner, Amy Rosenbluth Basic ES Cell Biology The primary project in the laboratory focuses on basic biology of embryonic stem (ES) cells. Mouse ES cells were first isolated in 1981, and found to be pluripotent in differentiation while maintaining the capacity for indefinite self-renewal. Although expectation is very high for the use of ES cells or a similar pluripotent cell population as a source of cell-based transplantation therapy in the clinical setting, the use of ES cells as a tool for basic science should also not be overlooked. ES cells differentiate on culture dishes, at least in part, by recapitulating the processes seen in embryonic development. Using this in vitro differentiation of ES cells, we have been studying molecular mechanisms underlying early embryonic cell fate specification. In particular, we focus on the differentiation process of ES cells into extraembryonic primitive endoderm (see the Figure below), which represents the event occurring within the inner cell mass of E3.5 blastocysts. By revealing the mechanisms as to how ES cells retain or lose pluripotency, the study will provide us with critical insight regarding how stem cells self-renew or differentiate in general. Of interest, we and others recently demonstrated that both mouse and human ES cells are not homogeneous in cell culture but have multiple and overlapping heterogeneity. Moreover, these heterogeneities appear to be essential and play a critical role for ES cell maintenance. Currently, we are elucidating a biphasic role of the FGFR signaling in ES cell differentiation and self-renewal. Germ Cells, Cancer, Epigenetics Another major focus of the lab is on mitochondrial adenine nucleotide translocases (ANTs), which mediate the exchange of ADP and ATP on the inner mitochondrial membrane, thus essential for energy metabolism in eukaryotic cells. Until recently, it has been believed that humans posses three members of the ANT family of genes, whose transcription depends on tissue type, developmental stage, cell proliferation, and hormone status etc. We have recently identified the fourth member of ANT, ANT4, through ES cell research, and determined that it is expressed exclusively in male germ cells and is particularly high during meiosis. ANT4 is conserved only in mammals, suggesting a unique and indispensable role for this ADP/ATP carrier in mammalian germ cell development. By generating Ant4 deficient mice, we recently determined that Ant4 is essential for male germ cell meiosis and subsequent male fertility. Although chromosomal localization of ANT family genes indicates that ANT4 may be compensating the inactivation of the X chromosome-linked ANT2 gene during male meiosis, ANT4 has a distinct protein structure compared to other somatic ANTs. To this end, we are currently working under the hypothesis that ANT4 has been uniquely adapted to mammalian spermatogenesis and sperm function. A distinct structure of ANT4 peptide has also enabled us to predict small compounds to specifically inhibit ANT4 using a molecular docking approach. We may be able to prove these lead compounds useful for developing male contraceptives. Further, our recent study on transcriptional regulation of the Ant4 gene is revealing a common molecular mechanism as to how meiosis-specific genes are repressed in somatic tissues. Since the aberrant expression of meiosis specific genes may lead to mitotic catastrophe and predispose cells to oncogenic transformation, the study would become significant in cancer biology as well. Curriculum Vitae (click to download MS-Word document) Selected Publications Germ Cells and Stem Cells
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