| Send E-mail to: zborok@usc.edu | |
| Telephone: 323-226-7923 | Fax: 323-442-2611 |
| Office: HMR-911 | Mail Code: 9520 HSC |
Education:
MB ChB 1979 Medicine - University of Cape Town, South Africa
Postdoctoral Research Fellowship:
1981-1982 College of Physicians and Surgeons of Columbia University
Started at USC: 1990
Research Topics: Gene Regulation/Transcription, Gene Therapy, Stem Cell Biology
Research Description
My research is focussed on dissecting transcriptional mechanisms that regulate differentiation of lung alveolar epithelial cells in the context of lung injury and repair. The normal alveolar epithelial lung lining consists of two highly differentiated cell types, type II and type I cells. Type II cells normally serve as progenitors for themselves and also give rise to type I cells, whereas type I cells have been viewed as being terminally differentiated. Failure of type II cells to give rise to type I cells may give rise to abnormal repair of the lung leading to failure of re-epithelialization and pulmonary fibrosis. Using an in vitro culture model, we have demonstrated that isolated type II alveolar epithelial cells in culture undergo transdifferentiation towards a type I cell phenotype recapitulating the situation in vivo following injury. Furthermore, the transdifferentiation process is reversible by certain culture conditions indicating that maintenance of alveolar epithelial cell phenotype is actively regulated and suggesting considerable plasticity of alveolar epithelial cell phenotype. The molecular mechanisms that regulate transitions between the two cell types in the adult have not been elucidated. We are investigating the role of the transcriptionfactors GATA-6 and FoxP2 on regulating expression of the differentiated alveolar epithelial cell phenotype and on modulating phenotypic transitions between type II and type II cells. To do this, we are investigating interactions of these transcription factors with cell-specific genes, aquaporin-5 and surfactant protein-C, and evaluation effects of overexpression of inhibition of these factors on cell phenotype. In addition, we have recently demonstrated that alveolar epithelial cells treated with TGF-ß undergo epithelial-mesenchymal transition to a myofibroblast phenotype and have initiated studies to determine the transcriptional mechanisms underlying this phenotypic change with particular emphasis on interaction between TGF-ß and Wnt/ß-catenin pathways.
Selected Publications
Liebler JM, Lutzko C, Banfalvi A, Senadheera D, Aghamohammadi N, Crandall ED, Borok Z. - RETENTION OF HUMAN BONE MARROW-DERIVED CELLS IN MURINE LUNGS FOLLOWING BLEOMYCIN-INDUCED LUNG INJURY. - Am J Physiol Lung Cell Mol Physiol [ 2008 ] May 30; . PubMed
Zhou B, Ann D, Flodby P, Minoo P, Liebler JM, Crandall ED Ph D M D, Borok Z. - RAT AQUAPORIN-5 4.3-kb 5'-FLANKING REGION DIFFERENTIALLY REGULATES EXPRESSION IN SALIVARY GLAND AND LUNG IN VIVO. - Am J Physiol Cell Physiol [ 2008 ] Apr 30; . PubMed
Bahhady R, Kim KJ, Borok Z, Crandall ED, Shen WC. - Characterization of protein factor(s) in rat bronchoalveolar lavage fluid that enhance insulin transport via transcytosis across primary rat alveolar epithelial cell monolayers. - Eur J Pharm Biopharm [ 2008 ] Feb 6; . PubMed
Yacobi NR, Demaio L, Xie J, Hamm-Alvarez SF, Borok Z, Kim KJ, Crandall ED. - Polystyrene nanoparticle trafficking across alveolar epithelium. - Nanomedicine [ 2008 ] Jun;4(2):139-45 . PubMed
Zhou B, Zhong Q, Minoo P, Li C, Ann DK, Frenkel B, Morrisey EE, Crandall ED, Borok Z. - Foxp2 inhibits Nkx2.1-mediated transcription of SP-C via interactions with the Nkx2.1 homeodomain. - Am J Respir Cell Mol Biol [ 2008 ] Jun;38(6):750-8 . PubMed
Minoo P, Hu L, Zhu N, Borok Z, Bellusci S, Groffen J, Kardassis D, Li C. - SMAD3 prevents binding of NKX2.1 and FOXA1 to the SpB promoter through its MH1 and MH2 domains. - Nucleic Acids Res [ 2008 ] Jan;36(1):179-88 . PubMed
Uchiyama T, Fujita T, Gukasyan HJ, Kim KJ, Borok Z, Crandall ED, Lee VH. - Functional characterization and cloning of amino acid transporter B(0,+) (ATB(0,+)) in primary cultured rat pneumocytes. - J Cell Physiol [ 2008 ] Mar;214(3):645-54 . PubMed
Bates SR, Tao JQ, Yu KJ, Borok Z, Crandall ED, Collins HL, Rothblat GH. - Expression and biological activity of ABCA1 in alveolar epithelial cells. - Am J Respir Cell Mol Biol [ 2008 ] Mar;38(3):283-92 . PubMed
Qiao R, Yan W, Clavijo C, Mehrian-Shai R, Zhong Q, Kim KJ, Ann D, Crandall ED, Borok Z. - Effects of KGF on alveolar epithelial cell transdifferentiation are mediated by JNK signaling. - Am J Respir Cell Mol Biol [ 2008 ] Feb;38(2):239-46 . PubMed
Patel LN, Uchiyama T, Kim KJ, Borok Z, Crandall ED, Shen WC, Lee VH. - Molecular and functional expression of multidrug resistance-associated protein-1 in primary cultured rat alveolar epithelial cells. - J Pharm Sci [ 2008 ] Jun;97(6):2340-9 . PubMed
