Steven M. Dubinett, M.D.
Chief, Pulmonary and Critical Care Medicine
Professor of Medicine and Pathology
Director, UCLA Lung Cancer Research Program

Address:
Division of Pulmonary and Critical Care Medicine
David Geffen School of Medicine at UCLA
37-131 Center for Health Sciences
10833 Le Conte Avenue
Los Angeles, CA 90095-1690

Contact Information :
Office: 310-267-2725
Fax: 310-267-2829

Email:

sdubinett@mednet.ucla.edu
Assistant:
lwinter@mednet.ucla.edu


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Education and Training:

Education:
M.D., New Jersey Medical School

Clinical Research and Training:
Fellowship, Pulmonary and Critical Care, Massachusettes General Hospital
Research Fellowship, Pathology, Harvard University
Residency, Internal Medicine, UCLA SFVP


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Areas of Interest

  • Inflammation dependent regulation of tumor development and progression in lung cancer
  • Lung cancer chemoprevention and early detection
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Representative Publications:

Miller PW, Sharma S, Stolina M, Butterfield L, Luo J, Lin Y, Dohadwala M, Batra RK, Wu L, Economou JS, Dubinett SM.  Intratumoral administration of adenoviral interleukin-7 gene-modified dendritic cells augments specific antitumor immunity and tumor eradication.  Human Gene Therapy 2000; 11: 53-65.

Stolina M, Sharma S, Lin Y, Dohadwala M, Gardner B, Luo J, Zhu L, Kronenberg M, Miller PW, Lee J, Dubinett SM. Specific inhibition of cyclooxygenase 2 restores antitumor immunity by altering the balance of IL-10 and IL-12 synthesis. Journal of Immunology 2000; 164: 361-70.

Sharma S, Stolina M, Luo J, Strieter RM, Burdick M, Zhu LX, Batra RK, Dubinett SM.  SLC/6Ckine mediates T cell-dependent antitumor responses in vivo.  Journal of Immunology 2000, 164: 4558-4563.

Zhu L, Sharma S, Stolina M, Gardner B, Roth MD, Tashkin DP, Dubinett SM.  Tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. Journal of Immunology 2000, 165: 373-380.

Dohadwala M, Luo J, Zhu L, Lin Y, Dougherty GJ, Sharma S, Huang M, Põld M, Batra RK, Dubinett SM.  Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44.  Journal of Biological Chemistry 2001, 276: 20809-20812.

Sharma S, Stolina M, Zhu L, Lin Y, Batra R, Huang M, Strieter R, Dubinett SM.  Secondary Lymphoid Chemokine reduces pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma.  Cancer Res 2001, 61: 6406-6412.

Huang M, Batra RK, Kogai T, Lin YQ, Hershman JM, Lichtenstein A, Sharma S, Zhu LX, Brent GA, Dubinett SM. Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non-small cell lung cancer.  Cancer Gene Ther 2001, 8: 612-618. 

Huang M, Sharma S, Zhu LX, Luo J, Keane MP, Burdick MD, Lin YQ, Dohadwala M, Batra RK, Strieter RM, Dubinett SM.  Interleukin-7 inhibits both TGF-b production and signaling in pulmonary fibrosis fibroblasts.  J. Clinical Invest 2002, 109: 931-937.

Dohadwala M, Batra RK, Luo J, Lin Y, Krysan K, Põld M, Sharma S, Dubinett SM.  Autocrine/Paracrine PGE2 production by NSCLC cells regulates MMP-2 and CD44 in COX-2-dependent invasion.  J Biol Chem 2002, 277:50828-50833.

Batra RK, Lin Y, Sharma S, Dohadwala M, Luo J, Pold M, Dubinett SM.  Non-small cell lung cancer-derived soluble mediators enhance apoptosis in T lymphocytes through an I kappa B kinase-dependent mechanism. Cancer Res 2003, 63: 642-646.

Heuze-Vourc'h N, Zhu L, Krysan K, Batra RK, Sharma S, Dubinett SM Abnormal IL-10Ra expression contributes to the maintenance of elevated COX-2 in non-small cell lung cancer cells.  Cancer Res 2003, 63: 766-770.

Sharma S, Stolina M, Baratelli F, Lin JF, Zhu L, Lin Y, Batra RK, Huang M, Dohadwala M, Dubinett SM.  Tumor COX-2-dependent regulation of murine dendritic cell function.  Clinical Cancer Res 2003, 9:961-968.

Zhu LX, Sharma S, Gardner B, Escuadro B, Atianzar K, Tashkin D, Dubinett SM.  IL-10 mediates the sigma receptor-dependent suppression of antitumor immunity.  J. Immunol 2003, 170:3585-3591.

Sharma S, Yang C, Zhu LX, Batra RK, Strieter RM, Dubinett SM.  The Secondary Lymphoid Tissue Chemokine (SLC)-mediated antitumor response requires the in vivo induction of interferon inducible protein-10 (IP-10) and monokine induced by interferon gamma (MIG).  Mol Cancer.  2003, 2:22.

Zhang L, Sharma S, Zhu LX, Kogai T, Hershman JM, Brent GA, Dubinett SM, Huang M.  Non-radioactive Iodide Effectively Induces Apoptosis in Genetically Modified Lung Cancer Cells.  Cancer Research.  2003, 63:5065-5072.

Sharma S, Batra RK, Yang SC, Hillinger S, Zhu L, Atianzar K, Strieter RM, Riedl K, Huang M, Dubinett SM.  IL-7 Gene Modified Dendritic Cells Reduce Pulmonary Tumor Burden in Spontaneous Murine Bronchoalveolar Cell Carcinoma.  Human Gene Therapy 2003, 14:1511-24.

Riedl K, Baratelli F, Batra R, Yang SC, Luo J, Escuadro B, Figlin R, Strieter R, Sharma S, Dubinett SM.  Overexpression of CCL-21/Secondary Lymphoid Tissue Chemokine in Human Dendritic Cells Augments Chemotactic Activities for Lymphocytes and Antigen Presenting Cells.  Molecular Cancer 2003, 2:35.

Krysan K, Merchant FH, Zhu L, Dohadwala M, Luo J, Lin Y, Heuze-Vourc’h N, Pold M, Seligson D, Chia D, Goodglick L, Wang H, Strieter R, Sharma S, Dubinett SM. COX-2-dependent stabilization of survivin in non-small cell lung cancer.  FASEB Journal 2004, 18(1):206-8. 

Hillinger S, Yang SC, Zhu L, Huang M, Duckett R, Atianzar K, Batra RK, Strieter RM, Dubinett SM, Sharma S.  Epstein Barr Virus-Induced Molecule 1 Ligand Chemokine (ELC/CCL19) Promotes IFNg-dependent Antitumor Responses in a Lung Cancer Model.  Journal of Immunology 2003, 171:6457-6456.

Mao JT, Roth MD, Serio KJ, Baratelli F, Zhu L, Holmes EC, Strieter RM, Dubinett SM.  Celecoxib modulates the capacity for PGE2 and IL-10 production in alveolar macrophages.  Clinical Cancer Research 2003, 9:5835-5841.

Dubinett SM, Sharma S, Huang M, Pold M, Mao JT.  Cyclooxygenase-2 in lung cancer.  Prog Exp Tumor Res. 2003, 37:138-62.

Pold M, Zhu L, Sharma S, Burdick M, Ying L, Lee PN, Pold A, Luo J, Krysan K, Dohadwala M, Mao J, Batra RK, Strieter RM, Dubinett SM.   Cyclooxygenase-2 dependent expression of angiogenic CXC chemokines, ENA-78/CXCL5 and IL-8/CXCL8, in human non-small cell lung cancer.  Cancer Research 2004, 64:1853-1860.

Yang SC, Hillinger S, Riedl K, Zhang L, Zhu L, Huang M, Atianzar K, Kuo BY, Gardner B, Batra RK, Strieter RM, Dubinett SM, Sharma S.  Intratumoral administration of dendritic cells overexpressing CCL21 generates systemic antitumor responses and confers tumor immunity.  Clinical Cancer Research 2004, 10:2891-2901.

Zhang L, Keane MP, Zhu LX, Sharma S, Rozengurt E, Strieter RM, Dubinett SM, Huang M.  IL-7 and TGF-b play counter-regulatory roles in PKC-d-dependent control of fibroblast collagen synthesis in pulmonary fibrosis.  Journal of Biological Chemistry 2004, 2; 279(27): 28315-9.

Pold M, Krysan K, Pold A, Dohadwala M, Heuze-Vourc’h N, Mao JT, Riedl K, Sharma S, Dubinett SM.  Cyclooxygenase-2 modulates the insulin-like growth factor axis in non-small cell lung cancer.  Cancer Research 2004; 64:6549-6555.

Krysan K, Dalwadi H, Sharma S, Pold M, Dubinett SM.  Cyclooxygenase 2-dependent expression of survivin is critical for apoptosis resistance in non-small cell lung cancer.  Cancer Research 2004; 64:6359-6362.

Baratelli F, Heuze-Vourc’h N, Krysan K, Dohadwala M, Riedl K, Sharma S, Dubinett SM. Prostaglandin E2-dependent enhancement of tissue inhibitors of metalloproteinases-1 production limits dendritic cell migration through extracellular matrix.  Journal of Immunology 2004, 173:5458-5466.

Sharma S, Yang SC, Zhu L, Reckamp K, Gardner B, Baratelli F, Huang M, Batra RK, Dubinett SM.  Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer.  Cancer Research 2005; 65(12): 5211-20.

Baratelli F, Krysan K, Heuze-Vourc’h N, Zhu L, Escuadro B, Sharma S, Reckamp K, Dohadwala M, Dubinett SM.  PGE2 confers survivin-dependent apoptosis resistance in human monocyte-derived dendritic cells.  J Leukoc Biol. 2005; 78(2):555-64.

Sharma S, Zhu L, Hillinger S, Yang SC, Atianzar K, Gardner B, Kuo B, Riedl K, Strieter RM, Batra RK, Huang M, Dubinett SM.  COX-2 inhibition promotes IFNg-dependent enhancement of anti-tumor immunity.  Journal of Immunology 2005; 175(2): 813-9.

Krysan K, Reckamp K, Dalwadi H, Sharma S, Rozengurt E, Dohadwala M, Dubinett S.  PGE2 activates MAPK/Erk pathway signaling and cell proliferation in non-small cell lung cancer cells in an EGF receptor-independent manner.  Cancer Research 2005; 65(14): 6275-6281.

Baratelli F, Lin Y, Zhu L, Yang SC, Hueze-Vourch N, Zeng G, Reckamp K, Dohadwala M, Sharma S, Dubinett SM.  PGE2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells.  Journal of Immunology. 2005; 175: 1483–1490.

Dalwadi H, Krysan K, Heuze-Vourc'h N, Sharma S, Dohadwala M, Riedl K, Cacalano N, Dubinett SM.  Cyclooxygenase 2 dependent regulation of STAT3 pathways in NSCLC.  Clin Cancer Res 2005; 11(21): 7674-82.

Weinberg OK, Marquez-Garban DC, Fishbein MC, Goodglick, L, Garban HJ, Dubinett SM, Pietras RJ. Aromatase inhibitors in human lung cancer therapy.  Cancer Res 2005; 65(24): 11287-91.

Mao JT, Fishbein MC, Adams B, Roth MD, Goodglick L, Hong L, Burdick M, Strieter RM, Holmes EC, Tashkin DP, Dubinett SM.  Celecoxib decreases Ki-67 proliferative index in active smokers.  Clinical Cancer Res. 2006; 12 (1): 314-20.

Zhang L, Sharma S, Hershman JM, Brent GA, Dubinett SM, Huang M.  Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation.  Cancer Gene Ther. 2006; (1): 74-81.

Yang SC, Batra RK, Hillinger S, Reckamp KL, Strieter RM, Dubinett SM, Sharma S.  Intrapulmonary administration of CCL21 gene-modified dendritic cells reduces tumor burden in spontaneous murine bronchoalveolar cell carcinoma.  Cancer Res. 2006; 66 (6): 3205-13.

Hillinger S, Yang SC, Batra RK, Strieter RM, Weder W, Dubinett SM, Sharma S.  CCL19 reduces tumor burden in a model of advanced lung cancer.  Br J Cancer 2006; 94(7): 1029-34.

Dohadwala M, Yang SC, Luo J, Sharma S, Batra RK, Huang M, Lin Y, Goodglick L, Krysan K, Fishbein MC, Hong L, Lai C, Cameron RB, Gemmill RM, Drabkin HA, Dubinett SM.  Cyclooxygenase-2-dependent regulation of E-cadherin: prostaglandin E2 induces transcriptional repressors ZEB1 and Snail in non small cell lung cancer.  Cancer Res. 2006; 66(10): 5338-45.

Reckamp KL, Krysan K, Morrow JD, Milne, GL, Newman RA, Tucker C, Elashoff RM, Dubinett SM*, Figlin RA*.  A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer.  Clin. Cancer Res. 2006; 12(11): 3381-3388. (*Joint senior authorship).

Su H, Bodenstein C, Dumont RA, Seimbille Y, Dubinett SM, Phelps ME, Herschman H, Czernin J, Weber W.  Monitoring tumor glucose utilization by positron emission tomography for prediction of treatment response to epidermal growth factor receptor kinase inhibitors.  Clin. Cancer Res. 2006; 12(19): 5659-5667.

Zeng G, Aldridge ME, Tian X, Seiler D, Zhang X, Jin Y, Rao J, Li W, Chen D, Langford MP, Duggan C, Belldegrun AS, Dubinett SM.  Dendritic cell surface calreticulin is a receptor for NY-ESO-1: direct interactions between tumor-associated antigen and the innate immune system.  J Immunol. 2006; 177(6): 3582-9.

Cui X, Zhang L, Luo J, Rajasekaran A, Hazra S, Cacalano N, Dubinett SM.  Unphosphorylated STAT6 contributes to constitutive cyclooxygenase-2 expression in human non-small cell lung cancer.  Oncogene 2007; 26(29): 4253-60.

Hazra S, Batra RK, Tai HH, Sharma S, Cui X, Dubinett SM.  Pioglitazone and Rosiglitazone decrease PGE2 in non-small cell lung cancer cells by upregulating 15-hydroxyprostaglandin dehydrogenase.  Mol Pharmacol. 2007; 71(6):1715-20.

Liu M, Yang SC, Sharma S, Luo J, Cui X, Huang M, Ramirez RD, Shay JW, Minna JD, Dubinett SM.  TGF-b1 and EGF modulate transcriptional and post-transcriptional expression of cyclooxygenase-2 in immortalized human bronchial epithelial cells.  Am J Respir Cell Mol Biol. 2007; 37(5): 578-88.

Krysan K, Lee JM, Dohadwala M, Gardner BK, Reckamp KL, Garon E, St. John M, Sharma S, Dubinett SM.  Inflammation, epithelial to mesenchymal transition, and epidermal growth factor receptor tyrosine kinase inhibitor resistance.  J Thorac. Oncol. 2008; 3(2): 107-110.

Reckamp KL, Gardner BK, Figlin RA, Elashoff D, Krysan K, Dohadwala M, Mao J, Sharma S, Inge L, Rajasekaran A, Dubinett SM.  Tumor response to combination celecoxib and erlotinib therapy in non-small cell lung cancer is associated with a low baseline matrix metalloproteinase-9 and a decline in serum soluble E-cadherin.  J Thorac. Oncol. 2008; 3(2): 117-124.

Baratelli F, Takedatsu H, Hazra S, Peebles K, Luo J, Kurimoto P, Zeng, G, Batra RK, Sharma S, Dubinett SM, Lee JM.  Pre-clinical characterization of GMP grade CCL21-gene modified dendritic cells for application in a phase I trial in Non- Small Cell Lung Cancer.  J Transl Med. 2008 Jul 22; 6(1):38.



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