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Wade Gutierrez, M5G

wade-gutierrez@uiowa.edu

 

MSTP Learning Community:  Bean

MSTP Entry Date:  June 9, 2016

PhD Program:

Cancer Biology

Mentor:

Rebecca Dodd, PhD

Graduate Profile Lab Website

Epigenetic Combination Therapy Improves Survival in Soft Tissue Sarcoma by a Novel Mechanism

Sarcomas are a diverse group of connective tissue tumors comprising approximately 1% of adult cancers and 15% of pediatric cancers. The profound heterogeneity of sarcomas presents a unique challenge when trying to understand and treat these malignancies. To date, few molecular targets have been identified for chemotherapeutic treatment. In collaboration with a Phase 1b clinical trial at the University of Iowa, we are investigating a novel combination therapy using standard-dose Gemcitabine (Gem), an antimetabolite, with low-dose Decitabine (DAC), a DNA methyltransferase inhibitor, for the treatment of soft-tissue sarcoma. To test the efficacy of Gem+DAC combination treatment and to elucidate its therapeutic mechanism, we are using primary and orthotopic allograft mouse models of undifferentiated pleomorphic sarcoma (UPS), one of the most common forms of adult soft tissue sarcoma. Gem+DAC combination therapy slows tumor growth better than single agent alone in both primary and syngeneic UPS mouse models. Previous studies have shown that low-dose DAC exerts therapeutic effects by promoting anti-tumor immune activation. However, our data show that the combination therapy is working in a previously undescribed immune-independent manner. The findings from our mouse models will provide guidance as we conduct a co-clinical trial examining biological correlates of treatment efficacy using patient samples from our Phase 1b clinical trial collaboration.


Committees:

  • 2016-present - CCOM Medical School Ambassador
  • 2016-present - Student Member, American Medical Association (AMA)
  • 2017-present - CCOM Student Representative, Association of American Medical Colleges (AAMC) Organization of Student Representatives (OSR)
  • 2018-present - Affiliate Member, University of Iowa Holden Comprehensive Cancer Center
  • 2018-present - Associate Member, American Association for Cancer Research (AACR)
  • 2018-present - Member, Sarcoma Foundation of America
  • 2018-present - Full Member, American Physician Scientist Association (APSA)
  • 2019-present - MSTP Student Panel Member, CCOM FUTURE in Biomedicine Program
  • 2019-2020 - AAMC - Organization of Student Representatives
  • 2016-2017 - MSTP Recruitment Committee
  • 2016-2019 - MSTP Applicant Task Force
  • 2018 – Summer Undergraduate MSTP Research (SUMR) Program Student Mentor
  • 2019 - Summer Undergraduate MSTP Research (SUMR) Program Student Mentor

Awards:

  • 2016 - Sloan Scholar, Alfred P. Sloan Foundation Minority PhD (MPHD) Program, Sloan Center for Exemplary Mentoring, University of Iowa
  • 2018 - Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), Department of Pharmacology, University of Iowa
  • 2018 - HCCC Affiliate Member, Experimental Therapeutics
  • 2019 - Fellowship re-appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795)
  • 2020 - HCCC Retreat winner for Clinical Trials & Cancer Outcomes:  Epigenetic Combination Therapy Improves Survival in Soft Tissue Sarcoma by a Novel Immune-independent Mechanism
  • 2020 - Midwest Tumor Microenvironment Meeting Young Investigator Award

Education:

2016 - BS, Psychology - Kansas State University

Publications:

ORCiD:  0000-0002-0643-3566

Kruspe S, Dickey DD, Urak KT, Blanco GN, Miller MJ, Clark KC, Burghardt E, Gutierrez WR, Phadke SD, Kamboj S, Ginader T, Smith BJ, Grimm SK, Schappet J, Ozer H, Thomas A, McNamara JO 2nd, Chan CH, Giangrande PH. Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology. Mol Ther Nucleic Acids. 2017 Sep 15;8:542-557. doi: 10.1016/j.omtn.2017.08.004. Epub 2017 Aug 12. PMCID: PMC5577414.

Kerov V, Laird JG, Joiner ML, Knecht S, Soh D, Hagen J, Gardner SH, Gutierrez W, Yoshimatsu T, Bhattarai S, Puthussery T, Artemyev NO, Drack AV, Wong RO, Baker SA, Lee A. α(2)δ-4 Is Required for the Molecular and Structural Organization of Rod and Cone Photoreceptor Synapses. J Neurosci. 2018 Jul 4;38(27):6145-6160. doi: 10.1523/JNEUROSCI.3818-16.2018. Epub 2018 Jun 6. PMCID: PMC6031576.

Urak KT, Blanco GN, Shubham S, Lin LH, Dassie JP, Thiel WH, Chen Y, Sonkar VK, Lei B, Murthy S, Gutierrez WR, Wilson ME, Stiber JA, Klesney-Tait J, Dayal S, Miller FJ Jr, Giangrande PH. RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome. Nat Commun. 2019 Jan 10;10(1):116. doi: 10.1038/s41467-018-08030-y. PubMed PMID: 30631065; PMCID: PMC6328615.

Scherer A, Stephens VR, McGivney GR, Gutierrez WR, Laverty EA, Knepper-Adrian V, Dodd RD. Distinct Tumor Microenvironments Are a Defining Feature of Strain-Specific CRISPR/Cas9-Induced MPNSTs. Genes (Basel). 2020 May 23;11(5). doi: 10.3390/genes11050583. PubMed PMID: 32456131; PubMed Central PMCID: PMC7288323.

Dodd RD, Scherer A, Huang W, McGivney GR, Gutierrez WR, Laverty EA, Ashcraft KA, Stephens VR, Yousefpour P, Saha S, Knepper-Adrian V, Floyd W, Chen M, Ma Y, Mastria EM, Cardona DM, Eward WC, Chilkoti A, Kirsch DG. Tumor Subtype Determines Therapeutic Response to Chimeric Polypeptide Nanoparticle-based Chemotherapy in Pten-deleted Mouse Models of Sarcoma. Clin Cancer Res. 2020 Sep 15;26(18):5036-5047. doi: 10.1158/1078-0432.CCR-19-2597. Epub 2020 Jul 27. PubMed PMID: 32718998; PubMed Central PMCID: PMC7641033.

Yong C, Moose DL, Bannick N, Gutierrez WR, Vanneste M, Svensson R, Breheny P, Brown JA, Dodd RD, Cohen MB, Henry MD. Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging. PLoS One. 2020;15(9):e0232807. doi: 10.1371/journal.pone.0232807. eCollection 2020. PubMed PMID: 32986721; PubMed Central PMCID: PMC7521703.

Gutierrez WR, Scherer A, McGivney GR, Brockman QR, Knepper-Adrian V, Laverty EA, Roughton GA, Dodd RD. Divergent immune landscapes of primary and syngeneic Kras-driven mouse tumor models. Sci Rep. 2021 Jan 13;11(1):1098. doi: 10.1038/s41598-020-80216-1. PMID: 33441747; PMCID: PMC7806664.

Kruspe S, Dickey DD, Urak KT, Blanco GN, Miller MJ, Clark KC, Burghardt E, Gutierrez WR, Phadke SD, Kamboj S, Ginader T, Smith BJ, Grimm SK, Schappet J, Ozer H, Thomas A, McNamara JO 2nd, Chan CH, Giangrande PH. Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology. Mol Ther Nucleic Acids. 2017 Sep 15;8:542-557. doi: 10.1016/j.omtn.2017.08.004. Epub 2017 Aug 12. PubMed PMID: 28918054; PubMed Central PMCID: PMC5577414.