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Derek Wainwright, PhD

Associate Professor, Depts. of Cancer Biology (Primary) and Neurological Surgery (Adjunct)

Scientific Director, Brain Tumor Research

Program Leader, Cancer Biology & Therapeutics, Cardinal Berrnadin Cancer Center

Research Interests:

  • Glioblastoma
  • Cancer immunology and immunotherapy
  • Aging and cancer
  • Neuroimmunology
  • Mechanisms of resistance to therapy for cancer

Bio

Our laboratory has 3 primary research goals. The FIRST goal is to understand how glioblastoma (GBM) cell indoleamine 2,3 dioxygenase 1 (IDO; IDO1) increases immunosuppressive T-reg infiltration, suppresses the immune response, and decreases overall survival in mouse models and human subjects with glioblastoma. Our previous work discovered that glioblastoma cell IDO1 non-enzymically upregulates immunosuppressive complement factor H (CFH) and factor H-like 1 (FHL-1) in human GBM cells, which in-turn, suppresses the anti-tumor immune response through intratumoral T-reg and MDSC accumulation. The SECOND goal is the active application of immunotherapy for patients with glioblastoma. Our group was the first to show that the simultaneous treatment with radiation, anti-PD-1 mAb, and pharmacological IDO1 enzyme inhibition leads to an unprecedented survival benefit in experimental models with intracranial brain tumors. This preclinical observation motivated the now ongoing phase I clinical trial of newly diagnosed glioblastoma patients treated with simultaneous radiation, nivolumab (anti-PD-1 mAb), and BMS-986205 (IDO1 enzyme inhibition) [NCT04047706]. The Wainwright Laboratory has performed the immunocorrelative profiling of patient-isolated PBMCs, tumor, stool, and serum that’s aimed at generating a predictive algorithm for stratifying responders [overall survival (OS) ≥20 months] versus non-responders (OS < 20 months). The THIRD goal is to better understand why older adults with glioblastoma die significantly faster as compared to younger adults with glioblastoma. We were the first group to show that advanced age increases immunosuppression in both the mouse and human brain. We were also the first to demonstrate that there is a functional consequence of increased immunosuppression in the aged brain that decreases the efficacy of immunotherapy with radiation, anti-PD-1 mAb, and IDO1 enzyme inhibitor treatment in older adults with GBM. Currently, our group is working with medicinal chemist, Dr. Gary Schiltz, PhD, to generate new drugs that aim to reverse immunosuppression in the aged brain (and simultaneously against tumor cells) of adults with glioblastoma.

The Wainwright Laboratory is an active training ground for students in high school, undergraduate school, graduate school, postdoctoral fellowship, medical school, and medical residency.

Wainwright Lab Donation Link

Education

  • BS in Biology and Music, Bradley University
  • MS, PhD in Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago
  • Postdoctoral fellowship, University of Chicago

Research Interests

  • Glioblastoma
  • Cancer immunology and immunotherapy
  • Aging and cancer
  • Neuroimmunology
  • Mechanisms of resistance to therapy for cancer

Publications/Research Listings

  • Age-stratified comorbid and pharmacologic analysis of patients with glioblastoma Rabin, EE; Huang, J; Kim M; Mozny A; Lauing, K; Penco-Campillo, M; Zhai, L; Bommi, P; Mi, X; Power, EA; Prabhu, VC; Anderson, DE; Barton, KP; Walunas, TL; Schlitz, GE; Amidei, C; Sanchez-Gomez, P; Thakkar, JP; Lukas, RV; Wainwright, DA Brain Behav Immun Health. 2024 Mar 15:38:100753. doi: 10.1016/j.bbih.2024.100753. eCollection 2024 Jul. PMID: 38600951; PMCID: 11004500
  • Advanced age in humans and mouse models of glioblastoma show decreased survival from extratumoral influence Johnson, M; Bell, A; Lauing KL; Ladomersky, E; Zhai, L; Penco-Campillo, M; Shah, Y; Mauer, E; Xiu, J; Nicolaides, T; Drumm, M; McCortney, K; Elemento, O; Kim, M; Bommi, P; Low, JT; Memon, R; Wu, J; Zhao, J; Mi, X; Glantz, MJ; Sengupta S; Castro, B; Yamini, B; Horbinski, C; Baker, DJ; Walunas, TL; Schiltz, GE; Lukas, RV; Wainwright, DA Clin Cancer Res. 2023 Sep 19. doi: 10.1158/1078-0432.CCR-23-0834. Online ahead of print. PMID: 37725593
  • Identification and characterization of a novel IDO PROTAC for patients with glioblastoma Bollu, L.R., Bommi, P.V., Monsen, P.J., Zhai, L., Bell, A., Lauing, K.L., Bell, A., Kim, M., Ladomersky, E., Yang, X., Platanias, L.C., Matei, D.E., Bonini, M.G., Munshi, H.G., Hashizume, R., Wu, J.D., Zhang, B., James, C.D., Chen, P., Kocherginsky, M., Horbinski, C., Cameron, M.D., Girgorescu, A.A., Yamini, B., Lukas, R.V., Schiltz, G.E., *Wainwright, D.A. 2022.  Journal
    of Medicinal Chemistry. 65(23):15642-15662. PMID: 36410047
  • Tumor cell IDO enhances immune suppression and decreases survival independent of tryptophan metabolism in glioblastoma Zhai, L; Bell, A; Ladomersky, E; Lauing, KL; Bollu, L; Nguyen, B; Genet, M; Kim, M; Chen, P; Mi, X; Wu, JD; Schipma, MJ; Wray, B; Griffiths, J; Unwin, RD; Clark, SJ; Acharya, R; Bao, R; Horbinski, C; Lukas, RV; Schiltz, GE; Wainwright, DA Clinical Cancer Research  2021 Dec 1;27(23):6514-6528. doi: 10.1158/1078-0432.CCR-21-1392. Epub 2021 Sep 3. PMID: 34479957; PMCID: PMC8639612
  • Advanced age increases immunosuppression in the brain and decreases immunotherapeutic efficacy in subjects with glioblastoma Ladomersky, E; Zhai, L; Lauing, KL; Bell, A; Xu, J; Kocherginsky, M; Zhang, B; Wu, JD; Podojil, JR; Platanias, LC; Mochizuki, AY; Prins, RM; Kumthekar, P; Raizer, JJ; Dixit, K; Lukas, RV; Horbinski, C; Wei, M; Zhou, C; Pawelec, G; Campisi, J; Grohmann, U; Prendergast, GC; Munn, DH; Wainwright, DA Clinical Cancer Research  2020 Oct 1;26(19):5232-5245. doi: 10.1158/1078-0432.CCR-19-3874. Epub 2020 Jun 16. PMID: 32546647; PMCID: PMC7541490
  • Simultaneous radiation with anti-PD-1 and IDO1inhibitor treatment durable increases survival against advanced glioblastoma Ladomersky, E., Zhai, L., Lenzen, A., Lauing, K.L., Qian, J., Scholtens, D.M., Gritsina, G., Sun, X., Liu, Y., Yu, F., Gong, W., Liu, Y., Jiang, B., Tang, T., Patel, R., Platanias, L.C., James, C.D., Stupp, R., Lukas, R.V., Binder, D.C., *Wainwright, D.A. 2018. Clinical Cancer Research. 24(11):2559-2573. PMID: 29500275
  • IDO1 in cancer: a Gemini of immune checkpoints Zhai, L., Ladomersky, E., Lenzen, A., Nguyen, B., Patel, R., Lauing, K.L., Wu, M., *Wainwright, D.A. 2018. IDO1 in cancer: a Gemini of immune checkpoints. Cellular & Molecular Immunology. 15(5):447-457. PMID: 29375124
  • Infiltrating T cells increase IDO1 expression in glioblastoma and contribute to decreased patient survival. Zhai, L., Ladomersky, E., Lauing, K.L., Wu, M., Genet, M., Gritsina, G., Győrffy, B., Brastianos, P.K., Binder, D.C., Sosman, J.A., Giles, F.J., James, C.D., Horbinski, C., Stupp, R., *Wainwright, D.A. 2017.  Clinical Cancer Research. 23(21):6650-6660. PMID: 28751450
  • Non-tumor cell IDO1 predominantly contributes to enzyme activity and response to CTLA-4/PD-L1 inhibition in mouse glioblastoma Zhai, L., Ladomersky, E., Dostal, C.R., Lauing, K.L., Swoap, K., Billingham, L.K., Gritsina, G., Wu, M., McCusker, R.H., Binder, D.C., *Wainwright, D.A. 2017. Brain, Behavior
    and Immunity. 62:24-29. PMID: 28179106
  • Molecular Pathways: Targeting IDO1 and other tryptophan dioxygenases for cancer immunotherapy Zhai, L., Spranger, S., Binder, D.C., Gritsina, G., Lauing, K.L., Giles, F.J., *Wainwright, D.A. 2015. Clinical Cancer Research.
    21(24):5427-33. PMID: 26519060
  • Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4 and PD-L1 in mice with brain tumors Wainwright, D.A., Dey, M., Chang, A.L., Balyasnikova, I.V., Kwon Kim, C., Tobias, A., Cheng, Y., Kim, J.W., Qiao, J., Zhang, L., Han, Y., Lesniak, M.S. 2014. Clinical Cancer Research. 20(20):5290-301. PMID: 24691018
  • IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival Wainwright, D.A., Balyasnikova, I.V., Auffinger, B., Ahmed, A., Han, Y., Lesniak, M.S. 2012. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clinical Cancer Research.
    18(22):6110-21. PMID: 22932670

Additional Publications List