Associate Professor Pediatrics, Division of Neonatal-Perinatal Medicine, Medical School
Education & Training
- Postdoctoral Fellow
- University of Texas Southwestern Medical Center at Dallas
- Cell and Molecular Biology, University of Texas at Dallas, 1988
- Cell and Molecular Biology, University of Texas at Dallas, 1985
Areas of Interests
- Research Interest
- Hormonal, developmental, and cell-specific regulation of pulmonary surfactant proteins
Hormonal, developmental, and cell-specific regulation of pulmonary surfactant proteins
The research in my laboratory is directed at understanding the molecular mechanisms involved in (1) post-transcriptional regulation of pulmonary surfactant protein (SP-A and SP-B) mRNA, and (2) post-translational regulation of innate immunity proteins, like SP-A, of the lung in response to environmental insults.
With regards to analysis of SP-A and SP-B mRNA stability, we have found that the 3’-untranslated region (UTR) is key in the regulation of surfactant protein mRNA stability. We have identified short sequences that are necessary and sufficient for regulation. Our immediate goal is to identify the cellular components, such as proteins and microRNAs, that mediate these regulations.
With regards to analysis of SP-A protein expression, we have found that expression of SP-A is reduced in pulmonary epithelial cells exposed to respiratory syncytial virus (RSV) and particulate matter. The mechanisms underlying these responses is unknown, but we suspect that the virus either induces proteases that reduce SP-A levels or microRNA that reduces translation of SP-A.
A tutorial in my laboratory will provide experience in all methods of molecular biology, in mRNA manipulation and stability analysis, and protein manipulation and stability analysis. The student would also gain knowledge of cell culture techniques, of the culture of primary cells, and in techniques used to make recombinant replication-defective adenoviruses.
- Posey KL, Liu P, Wang HR, Veerisetty AC, Alcorn JL, Hecht JT. RNAi reduces expression and intracellular retention of mutant cartilage oligomeric matrix protein. PLoS One. 5:e10302, 2010.
- Wang D, Morales JE, Calame DG, Alcorn JL, Wetsel RA. Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice. Mol Ther. 18:625-34, 2010.
- Posey KL, Veerisetty AC, Liu P, Wang HR, Poindexter BJ, Bick R, Alcorn JL, Hecht JT. An inducible cartilage oligomeric matrix protein mouse model recapitulates human pseudoachondroplasia phenotype. Am J Pathol. 175:1555-63, 2009.
- Bruce, SR, Atkins, CL, Colasurdo GN, Alcorn JL. Respiratory Syncytial Virus (RSV) Infection Alters Surfactant Protein-A (SP-A) Expression in Human Pulmonary Epithelial Cells by Reducing Translation Efficiency. Am J Physiol Lung Cell Mol Physiol. 2009 [Epub ahead of print].
- Alcorn, JL, Merritt, TM, Farach-Carson, MC, Wang, HH, Hecht, JT. Ribozyme-mediated reduction of wild-type and mutant cartilage oligomeric matrix protein (COMP) mRNA and protein. RNA. 15:686-95, 2009.
- Huang, HW, Bi, W, Jenkins, GN, Alcorn, JL. Glucocorticoid regulation of human pulmonary surfactant protein-B mRNA stability involves the 3′-untranslated region. Am J Respir Cell Mol Biol. 38:473-82, 2008.
- Vidaeff, AC, Ramin, SM, Gilstrap, LC 3rd, Bishop, KD, Alcorn, JL. Impact of progesterone on cytokine-stimulated nuclear factor-kappaB signaling in HeLa cells. J Matern Fetal Neonatal Med. 20:23-8, 2007
- Brunelli, L, Cieslik, KA, Alcorn, JL, Vatta, M, Baldini, A. Peroxisome proliferator-activated receptor-delta upregulates 14-3-3 epsilon in human endothelial cells via CCAAT/enhancer binding protein-beta. Circ Res. 100:e59-71, 2007.
- Merritt, TM, R Bick, BJ Pointdexter, JL Alcorn and JT Hecht. Unique Matrix Structure in the Rough Endoplasmic Reticulum Cisternae of Pseudoachondroplasia Chondrocytes. Am J Pathology. 170:293-300, 2007.
- Merritt, TM, JL Alcorn, R Haynes and JT Hecht. Expression of Mutant Cartilage Oligomeric Matrix Protein in Human Chondrocytes Induces the Pseudoachondroplasia Phenotype. J Orthopaedic Res.. 24:700-707, 2006.
- Alcorn, JL, Stark, JM, Chiappetta, CL, Jenkins, G and Colasurdo, GN. Effects of RSV infection on Pulmonary Surfactant Protein (SP-A) in Cultured Human Type II Cells: Contrasting Consequences on SP-A mRNA and Protein. Am J Physiol: Lung Cell Mol Physiol, 289:L1113-1122, 2005.
- Phokela, SS, Peleg, S, Moya, FR and Alcorn, JL. Regulation of human pulmonary surfactant protein gene expression by 1 ,25-dihydroxyvitamin D3. Accepted for publication pending revision in the Am J Physiol: Lung Cell Mol Physiol., 289:L617-626, 2005.
- Romero EJ, Moya FR, Tuvim MJ,and Alcorn JL. Interaction of an Artificial Surfactant in Human Pulmonary Epithelial Cells. Ped. Pulmonology 39:167-177, 2005.
- Stark, JM, Khan AM, Chiapetta CL, Xue H, Alcorn JL, and Colasurdo GN. Immune and functional role of nitric oxide in a mouse model of RSV infection. J Infect. Dis. 191:387-395, 2005.
- Ramin SM, Vidaeff AC, Gilstrap LC 3rd, Bishop KD, Jenkins GN, Alcorn JL. The effects of dexamethasone and betamethasone on surfactant protein-B messenger RNA expression in human type II pneumocytes and human lung adenocarcinoma cells. Am J Obstet Gynecol. 190:952-959, 2004.
- Vidaeff AC, Ramin SM, Gilstrap LC 3rd, and Alcorn JL. In vitro quantification of dexamethasone-induced surfactant protein B expression in human lung cells. J Maternal-Fetal Neonatal Med. 15:155-159, 2004.
- Alcorn, JL, Islam KN, Young PP, Mendelson CR. Glucocorticoid Inhibition of Surfactant Protein A (SP-A) Gene Expression in Lung Type II Cells is Mediated via the TTF-1 Binding Element. Am J Physiol Lung Cell Mol Physiol. 286:L767-776, 2004.
- Mustafa SB, DiGeronimo RJ, Petershack JA, Alcorn JL, and SR Seidner. Postnatal Glucocorticoids Induce -ENaC Formation and Regulate Glucocorticoid receptors in the Preterm Rabbit Lung. Am J Physiol Lung Cell Mol Physiol. 286:L73-80, 2004.
- Vidaeff AC, Ramin SM, Gilstrap LC 3rd, Bishop KD, Jenkins GN, and Alcorn JL. Characterization of corticosteroid redosing in an in vitro cell line model. Am J Obstet Gynecol. 191:1403-1408, 2004.
- Shlykov SG, Yang M, Alcorn JL and Sanborn BM. Capacitative cation entry in human myometrial cells and augmentation by hTrpC3 overexpression. Biol Reprod. 69:647-655, 2003.
- Gao E, Wang Y, Alcorn JL, and Mendelson CR. Transcription factor USF2 is developmentally regulated in fetal lung and acts together with USF1 to induce surfactant protein-A (SP-A) gene expression. Am J Physiol Lung Cell Mol Physiol. 284:L1027-1036, 2003.
- Razeghi P, Young ME, Alcorn JL, Moravec CS, Frazier OH, and Taegtmeyer H. The failing heart reverts to a fetal gene profile by repressing metabolic genes. Circulation. 104:2923-2931. 2001.
- Alcorn JL, Hammer RE, Graves KR, Smith ME, Maika SD, Michael LF, Gao E, Wang Y, and Mendelson CR. Analysis of genomic regions involved in regulation of the rabbit surfactant protein A gene in transgenic mice. Am J Physiol: Lung Cell Mol Physiol. 277:L349-361. 1999.
- Mendelson CR, Gao E, Li J, Young PP, Michael LF, Alcorn JL. Regulation of expression of surfactant protein-A. Biochimica Et Biophysica Acta. 1408:132-149, 1998.
- Kamat A, Alcorn JL, Kunczt C, Mendelson CR. Characterization of the regulatory regions of the human aromatase (P450arom) gene involved in placenta-specific expression. Molecular Endocrinology. 12:1764-1777, 1998.
- Gao E, Wang Y, Alcorn JL, Mendelson CR. The basic helix-loop-helix-zipper transcription factor USF1 regulates expression of the surfactant protein-A gene. J Biol Chem. 272:23398-23406, 1997.
- Alcorn JL, Smith ME, Smith JF, Margraf LR, Mendelson CR. Primary cell culture of human type II pneumonocytes: maintenance of a differentiated phenotype and transfection with recombinant adenoviruses. Am J Respir Cell Mol Biol. 17:672-682, 1997.