Edwin Manuel, Ph.D. CV photo

Edwin Manuel, Ph.D.

  • Assistant Professor, Department of Experimental Therapeutics

Edwin Manuel, Ph.D.

Research Focus :
  • Development of therapeutic strategies to induce effective anti-tumor immune responses
  • Approaches to target immunosuppressive pathways to improve efficacy of cancer immunotherapy
  • Elucidating molecular mechanisms that drive transitions from benign disease to malignancy
  • 2011-2015, Senior Staff Scientist, Department of Experimental Therapeutics, City of Hope, Duarte, CA
  • 2008-2011, Postdoctoral Fellow, Department of Experimental Therapeutics, City of Hope, Duarte, CA
  • 2008, Harvard University, Cambridge, MA, Ph.D., Virology
  • 2002, San Diego State University, San Diego, CA, B.Sc. Microbiology

Tumor escape from immune recognition is an emerging hallmark of cancer that can significantly compromise the efficacy of current immunotherapeutic strategies.  Immune suppressive mechanisms within tumor-draining lymph nodes and the tumor microenvironment contribute to the ability of tumor cells to escape anti-tumor immunity.

In order to study the role of escape mechanisms within the tumor microenvironment, the laboratory of Edwin R. Manuel, Ph.D., has developed a versatile, Salmonella typhimurium (ST)-based platform that utilizes shRNA plasmid technology to target expression of proteins known to contribute to immune suppression.

One such protein, indoleamine 2,3-dioxygenase (IDO), is overexpressed in a variety of malignancies and has been shown to induce maturation of regulatory T cells and suppress tumor-reactive immune cells by virtue of its ability to deplete the essential amino acid tryptophan. Administration of ST targeting IDO (shIDO-ST) resulted in significant tumor-specific IDO-silencing and regression in preclinical models of melanoma and pancreatic cancer, which was dependent on activation of tumoricidal neutrophils. "Our group is currently using the shRNA-ST platform to target oncogenes involved in “oncogene addiction”, such as mutant KRAS in pancreatic cancer" states Dr. Manuel.

Another focus of Dr. Manuel’s research includes the use of checkpoint inhibitors to improve efficacy of cancer immunotherapies, specifically, therapeutic vaccines encoding for tumor antigens such as survivin and Wilms' tumor antigen 1 (WT1). "The overall objective of our research program will be to continue to generate novel approaches that overcome tumor escape to elicit potent anti-cancer immune responses, which can then be translated to the clinic for the treatment of aggressive cancers."

  • Salazar MA, ER Manuel, W Tsai, M D’Apuzzo, L Goldstein, BR Blazar, and DJ Diamond. Evaluation of innate and adaptive immunity contributing to the antitumor effects of PD1 blockade in an orthotopic murine model of pancreatic cancer. Oncoimmunol doi:10.1080/2162402X.2016.1160184. 2016.
  • J Chen, DJ Diamond, and ER Manuel. Developing Effective Salmonella-based Approaches to Treat Pancreatic Cancer. Pancreat Disord Ther 6: 167. 2016.
  • M Ouyang, EE White, H Ren, Q Guo, I Zhang, H Gao, S Yanyan, X Chen, Y Weng, AD Fonseca, ER Manuel, L Zhang, SL Vonderfecht, D Alizadeh, J Berlin, and B Badie. Metronomic doses of temozolomide enhance the efficacy of carbon nanotube CpG immunotherapy in an invasive glioma model. PLOS ONE. 11:e0148139. 2016.
  • ER Manuel, J Chen, M D’Apuzzo, MG Lampa, CB Thompson, TI Kaltcheva, T Ludwig, V Chung, and DJ Diamond. Salmonella-based therapy targeting indoleamine 2,3-dioxygenase coupled with enzymatic depletion of tumor hyaluronan completely regresses aggressive pancreatic tumors. Cancer Immun Res 3(9): 1096-107. 2015.
  • X Xu, WA Hegazy, L Guo, X Gao, AN Courtney, S Kurbanov, D Liu, G Tian, ER Manuel, DJ Diamond, M Hensel, and LS Metelitsa. Effective cancer vaccine platform based on attenuated Salmonella and a type III secretion system. Cancer Res 74, 6260-6270. 2014.
  • ER Manuel, BR Blazar, and DJ Diamond. Tumor growth control with IDO-silencing Salmonella-Reply. Cancer Res 14:4592-3. 2013.
  • ER Manuel and DJ Diamond.  A road less traveled paved by IDO silencing: Harnessing the antitumor activity of neutrophils. Author’s View. OncoImmunology 3:e23322-1,2. 2013.
  • CA Blache, *ER Manuel, TI Kaltcheva, AN Wong, JDI Ellenhorn, BR Blazar, and DJ Diamond. Systemic delivery of Salmonella typhimurium transformed with IDO shRNA enhances intratumoral vector colonization and suppresses tumor growth.  Cancer Res 24:6447-56. 2012. (*co-first author)
  • ER Manuel, CA Blache, JDI Ellenhorn, and DJ Diamond. Survivin the battle against immunosuppression. Author’s View. OncoImmunology 2: 240-1. 2012.
  • Fan H, IY Zhang, X Chen, L Zhang, H Wang, AC Carvalho da Fonseca, ER Manuel, DJ Diamond, AA Raubitschek, and B Badie. Intracerebral CpG immunotherapy with carbon nanotubes abrogates growth of subcutaneous melanomas in mice. Clin Cancer Res 20:5628-38. 2012.
  • ER Manuel, CA Blache, R Paquette, TI Kaltcheva, H Ishizaki, JD Ellenhorn, M Hensel, L Metelitsa, and DJ Diamond. Enhancement of cancer vaccine therapy by systemic delivery of a tumor targeting Salmonella-based Stat3 shRNA suppresses the growth of established melanoma tumors. Cancer Res 71:4183-91. 2011.
  • Ishizaki H, *ER Manuel, GY Song, T Srivastava, S Sun, DJ Diamond, and JD Ellenhorn. Modified vaccinia Ankara expressing survivin combined with gemcitabine generates specific antitumor effects in a murine pancreatic carcinoma model. Cancer Immunol Immun 60:99-109. 2011. (*co-first author)
  • Zhao D, D Alizadeh, L Zhang, W Liu, O Farrukh, ER Manuel, DJ Diamond, and B Badie. Carbon nanotubes enhance CpG uptake and potentiate antiglioma immunity. Clin Cancer Res 17:771-82. 2011.
  • Ishizaki H, GY Song, T Srivastava, K D Carroll, V Shahabi, ER Manuel, DJ Diamond, and JD Ellenhorn. Heterologous prime/boost immunization with p53-based vaccines combined with toll-like receptor stimulation enhances tumor regression. J Immunother 33:609-17. 2010.
  • ER Manuel, WW Yeh, H Balachandran, RH Clarke, MA Lifton, and NL Letvin. Vaccination reduces simian-HIV sequence reversion through enhanced viral control. J Virol 84:12782-9. 2010.
  • ER Manuel, Z Wang, Z Li, . La Rosa, W Zhou, and D J Diamond. Intergenic region 3 of MVA is a functional site for insert gene expression and allows for potent Ag-specific immune responses. Virology 403:155-62. 2010.
  • ER Manuel, WW Yeh, MS Seaman, K Furr, MA Lifton, SL Hulot, P Autissier, and NL Letvin. Dominant CD8+ T lymphocyte responses suppress expansion of vaccine-elicited subdominant T lymphocytes in rhesus monkeys challenged with pathogenic simian-human immunodeficiency virus. J Virol 83:10028-35. 2009.
  • J Li, T Srivastava, R Rawal, ER Manuel, D Isbell, W Tsark, C La Rosa, Z Wang, Z Li, PA Barry, KD Hagen, J Longmate, and DJ Diamond. Mamu-A01/K(b) transgenic and MHC Class I knockout mice as a tool for HIV vaccine development. Virology 387:16-28. 2009.
  • SL Hulot, M S Seaman, P Sen, PA Autissier, ER Manuel, and NL Letvin. Diverse cross-reactive potential and V{beta} gene usage of an epitope specific CTL population in monkeys immunized with diverse HIV-1 Env immunogens. J Virol 83:9803-12. 2009.
  • P Sen, WA Charini, RA Subbramanian, ER Manuel, MJ Kuroda, PA Autissier, and NL Letvin. Clonal focusing of epitope-specific CD8+ T lymphocytes in rhesus monkeys following vaccination and simian-human immunodeficiency virus challenge. J Virol 82:805-16. 2008.
  • ER Manuel, WA Charini, P Sen, FW Peyerl, MJ Kuroda, JE Schmitz, P Autissier, DA Sheeter, BE Torbett, and NL Letvin. Contribution of T-cell receptor repertoire breadth to the dominance of epitope-specific CD8+ T-lymphocyte responses. J Virol 80:12032-40. 2006.
  • FW Peyerl, DH Barouch, HS Bazick, ER Manuel, and NL Letvin. Use of molecular beacons for rapid, real-time, quantitative monitoring of cytotoxic T-lymphocyte epitope mutations in simian immunodeficiency virus. J Clin Microbiol 43:4773-9. 2005.
  • S Duensing, A Duensing, DC Lee, KM Edwards, SO Piboonniyom, ER Manuel, L Skaltsounis, L Meijer, and K Munger. Cyclin-dependent kinase inhibitor indirubin-3'-oxime selectively inhibits human papillomavirus type 16 E7-induced numerical centrosome anomalies. Oncogene 23:8206-15. 2004.
  • J Hasskarl, S Duensing, ER Manuel, and K Munger. The helix-loop-helix protein ID1 localizes to centrosomes and rapidly induces abnormal centrosome numbers. Oncogene 23:1930-8. 2004.

View all publications

  • American Association for the Advancement of Science (AAAS)
  • American Society for Microbiology (ASM)
  • American Association for Cancer Research (AACR)
  • Minority Biomedical Research Support (MBRS) Scholar
  • Dean’s List
  • Mortar Board National Honor Society
  • Golden Key Association Award
  • Phi Beta Kappa
  • Phi Kappa Phi
  • California Scholastic Federation
  • National Honor Society
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