Gomez-Gutierrez, Jorge G., Ph.D.

Education:Jorge G. Gomez-Gutierrez, PhD

B.Sc.,Biology, Autonomous University of Nuevo León, México. 2001
Ph.D., Biotechnology, Autonomous University of Nuevo León, México. 2006
Postdoctoral Fellowship, Department of Surgery, University of Louisville, USA; 2011

Curriculum Vitae

Current Positions:

Assistant Professor, The Hiram C. Polk Jr. M.D., Department of Surgery, University of Louisville
Member, James Graham Brown Cancer Center
Member, Tumor Immunobiology, University of Louisville

Contact Information:

505 South Hancock, KCCTR Building, room 452G
Louisville, KY, 40202
Phone: (502) 852-8464
Fax: (502) 852-3661

jgguti01@louisville.edu

Website:

https://www.linkedin.com/in/jorge-gomez-gutierrez-35691745

Research Description:

The Gomez-Gutierrez Laboratory is primarily interested in microbial-based cancer therapy. We focus on investigating how virus- and bacteria-based therapies can be used to stop tumorigenesis and induce oncolysis and/or immune responses in cancers when conventional therapy is inadequate. Two microorganisms are being studied: the first is a conditionally replicating adenovirus (CRAd) also known as oncolytic adenovirus (OAd); the second is the lactic acid bacteria Lactococcus lactis (L. lactis), which is generally regarded as a safe (GRAS) organism and is used in dairy industry to make cheese and yogurt. The former study is currently funded with an NIH/NCI exploratory/developmental grant R21CA210202.

     1.  Oncolytic Virotherapy

Oncolytic adenoviruses (OAds) are very promising for the treatment of cancer. However, OAd-based monotherapeutics have not meet expectations because the therapeutic activity has been limited exclusively to oncolytic cell death. However, the potency of OAds can be enhanced by combining them with highly genotoxic regimens such as chemotherapy, especially with those that induce autophagy (type-II programed cell death). In our laboratory, we have successfully demonstrated that chemotherapy-induced autophagy can enhance OAd efficacy in multiple cancer models.

 Oncolytic viruses (OVs) are believed to not only cause direct destruction of the tumor cells, but they also stimulate host anti-tumor immune responses. Thus far, the preclinical evaluation of OVs has been limited to mouse models without an immune system. The only other option for study is human OVs, but these do not multiply in murine tumor cells. We are taking a different approach in our laboratory. We strongly believe that the best way to test the safety and therapeutic potential of OVs is to use an animal model that is immunocompetent and supports an active viral infection, including both cell lysis and production of infectious viral progeny. We lead the way in identification of several murine cancer models that support virus replication and oncolysis. The use of these innovative models strengthens the robustness of our OV work.

     2.  Lactococcus lactis as gene delivery vehicle and/or as cancer vaccine agent.

Hypoxia is a component of the tumor microenvironment that reduces efficacy of both immuno- and chemotherapies resulting in poor clinical outcome. Therefore, we are exploiting the hypoxic microenvironment as a target for gene therapy, utilizing commensal facultative anaerobic bacteria. In other words, we are developing an effective and safe delivery system for cancer gene therapy by targeting the hypoxic tumor microenvironment with food-grade lactic acid bacteria (LAB) L. lactis. We have genetically engineered L. lactis to express fluorescent reporter genes. The expression of these reporter genes allow us to monitor the biodistribution of L. lactis and tumor accumulation via animal imaging.

Genetically modified L. lactis bacteria have been engineered as a tool to deliver bioactive proteins to mucosal tissues as a means to exert both local and systemic effects. We prefer L. lactis bacteria because of it is a common bacteria found in yogurt with no associated risk of toxicity and immunogenicity. We have successfully developed several strains of recombinant L. lactis expressing tumor-associated antigens or immunostimulatory molecules such as cytokines and chemokines. Preclinical studies have demonstrated promising antitumor efficacy.

Representative Publications:

-Gomez-Gutierrez JG, Elpek KG, Montes de Oca-Luna R, Shirwan H, Sam Zhou H, McMasters KM. Vaccination with an adenoviral vector expressing calreticulin-human papillomavirus 16 E7 fusion protein eradicates E7 expressing established tumors in mice. Cancer Immunol Immunother. 2007 Jul; 56(7):997-1007. PubMed PMID: 17146630.

-Villatoro-Hernandez J, Loera-Arias MJ, Gamez-Escobedo A, Franco-Molina M, Gomez-Gutierrez JG, Rodriguez-Rocha H, Gutierrez-Puente Y, Saucedo-Cardenas O, Valdes-Flores J, Montes-de-Oca-Luna R. Secretion of biologically active interferon-gamma inducible protein-10 (IP-10) by Lactococcus lactis. Microb Cell Fact. 2008 Jul 28;7:22. PMID: 18662403, PMCID: PMC2503953, DOI:10.1186/1475-2859-7-22

- Gomez-Gutierrez JG, Rao XM, Garcia-Garcia A, Hao H, McMasters KM, Zhou HS. Developing adenoviral vectors encoding therapeutic genes toxic to host cells: comparing binary and single-inducible vectors expressing truncated E2F-1. Virology. 2010 Feb 20;397(2):337-45. PubMed PMID: 20003994; PubMed Central PMCID: PMC2821996.   

- Gomez-Gutierrez JG, Garcia-Garcia A, Hao H, Rao XM, Montes de Oca-Luna R, Zhou HS, McMasters KM. Adenovirus-mediated expression of truncated E2F-1 suppresses tumor growth in vitro and in vivo. Cancer. 2010 Sep 15;116(18):4420-32. PubMed PMID: 20549818; PubMed Central PMCID: PMC4425364.  

- Rodriguez-Rocha H, Gomez-Gutierrez JG, Garcia-Garcia A, Rao XM, Chen L, McMasters KM, Zhou HS. Adenoviruses induce autophagy to promote virus replication and oncolysis. Virology. 2011 Jul 20;416(1-2):9-15. PubMed PMID: 21575980; PubMed Central PMCID: PMC3113480.

- Garcia-Garcia A, Rodriguez-Rocha H, Tseng MT, Montes de Oca-Luna R, Zhou HS, McMasters KM, Gomez-Gutierrez JG. E2F-1 lacking the transcriptional activity domain induces autophagy. Cancer Biol Ther. 2012 Sep;13(11):1091-101. PubMed PMID: 22825328; PubMed Central PMCID: PMC3462036.

Egger ME, McNally LR, Nitz J, McMasters KM, Gomez-Gutierrez JG. Adenovirus-mediated FKHRL1/TM sensitizes melanoma cells to apoptosis induced by temozolomide. Hum Gene Ther Clin Dev. 2014 Sep;25(3):186-95. PubMed PMID: 25238278; PubMed Central PMCID: PMC4227438.

Rangel-Colmenero BR, Gomez-Gutierrez JG, Villatoro-Hernández J, Zavala-Flores LM, Quistián-Martínez D, Rojas-Martínez A, Arce-Mendoza AY, Guzmán-López S, Montes-de-Oca-Luna R, Saucedo-Cárdenas O. Enhancement of Ad-CRT/E7-mediated antitumor effect by preimmunization with L. lactis expressing HPV-16 E7. Viral Immunol. 2014 Nov;27(9):463-7. PubMed PMID: 25216057.

Gomez-Gutierrez JG, Nitz J, Sharma R, Wechman SL, Riedinger, Martinez-Jaramillo E, Zhou HS, McMasters KM. Combined Therapy of Oncolytic Adenovirus and Temozolomide Enhances Lung Cancer Virotherapy In Vitro and In Vivo. Virology. 2016. Jan; 487:249-59.  PubMed PMID: 26561948.

Martinez-Jaramillo E, Garza-Morales R, Loera-Arias MJ, Saucedo-Cardenas O, Montes-de-Oca-Luna R, McNally LR, Gomez-Gutierrez JG. Development of Lactococcus lactis encoding fluorescent proteins, GFP, mCherry and iRFP regulated by the nisin-controlled gene expression system. Biotech Histochem. 2017;92(3):167-174.PMID:28318334 PMCID:PMC5638124 DOI:10.1080/10520295.2017.1289554

Garza-Morales R, Yaddanapudi K, Perez-Hernandez R, Riedinger E, McMasters KM, Shirwan H, Yolcu E, Montes de Oca-Luna R, Gomez-Gutierrez JG. Temozolomide renders murine cancer cells susceptible to oncolytic adenovirus replication and oncolysis. Cancer Biol Ther. 2018 Mar 4;19(3):188-197.PMID: 29252087. DOI:10.1080/15384047.2017.1416274

Martinez-Jaramillo E, Garza-Morales R, Wechman SL, Montes de Oca-Luna R, Saucedo-Cardenas O, Shirwan H, Yolcu E, McMasters KM, Gomez-Gutierrez JG. Adenovirus Lacking E1b Efficiently Induces Cytopathic Effect in HPV-16-Positive Murine Cancer Cells via Virus Replication and Apoptosis. Cancer Invest. 2018. 2;36(1):19-27.PMID:29388837 PMCID:PMC6088374 DOI:10.1080/07357907.2018.1430812

Garza-Morales R, Gonzalez-Ramos R, Chiba A, Montes de Oca-Luna R, McNally LR, McMasters KM, Gomez-Gutierrez JG. Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro. Cancers (Basel). 2018. 17;10(5). pii: E144.PMID:29772755 PMCID:PMC5977117 DOI:10.3390/cancers10050144

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