Research Interests
Research Topics
Immuno-Oncology, Cancer Immunotherapy, Chimeric Antigen Receptor (CAR)-T cells, T-cell Receptor-based therapy, Innate immune sensors, Cancer Biology
Disease Research Interests
Cancer, Drug Discovery
Research Description
The Ranoa lab aims to develop T cell receptor-based immunotherapy against solid tumors. Specifically, we intend to:
- define chimeric antigen receptor (CAR)-T cell-mediated mutual reprogramming of tumor and host immune cells in the tumor microenvironment using syngeneic murine tumor models;
- uncover a deep mechanistic understanding of the spatiotemporal and molecular factors that define pathways of resistance to CAR-T based therapies as well as determine the molecular mechanisms responsible for altering the functional states of host immune cells in the tumor; and
- engineer the next generation of CAR-T cells to be able to overcome immune suppression in solid tumors, improve its therapeutic efficacy both as a single agent and in combination with other treatment modalities, and reduce its adverse side effects.
To accomplish this, we will use CAR-T cells directed against tumors that display dysregulated antigens on their surface as our model system, perform in vitro co-culture assays and set up in vivo tumor models using both immune-competent and immuno-deficient mice. Common techniques used in the lab include basic molecular biology assays (such as genetic engineering, DNA/RNA/protein purification, flow cytometry, ELISA-based assays, RT-qPCR), tissue culture work (such as handling human and murine tumor cell lines, primary T cell purification from human and murine tissues, lentiviral and retroviral transduction of activated T cells, co-culture assays of tumor and effector T cells), animal work (such as establishing murine tumor models, administering treatment through various routes, breeding mice, isolating tissue samples for downstream processes), and big data analyses (such as bulk RNA sequencing, single-cell RNA sequencing, spatial transcriptomics, data mining).
Education
B.S. and M.S. in Molecular Biology and Biotechnology, University of the Philippines-Diliman, 2006
Ph.D. in Microbiology, University of Illinois at Urbana-Champaign, 2014
Postdoctoral Scholar, University of Chicago, 2014-2019
Research Fellow, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 2019-2024
Awards and Honors
2021: Recipient of Presidential Award and Medallion awarded to Pandemic response leaders, University of Illinois at Urbana-Champaign
2016: Outstanding research poster presentation at the 4th Post-Doctoral Association Symposium, University of Chicago
2010: DeBoer Graduate Research Fellowship in Microbiology, University of Illinois at Urbana-Champaign
2006: Winner of the Best Paper (Oral) Competition, at the 5th Asia-Pacific Biotechnology Congress and 35th Annual Convention of the Philippine Society for Micobiology, Inc.
Additional Campus Affiliations
Assistant Professor, Biochemistry
Highlighted Publications
Ranoa, D.R.E.; Sharma, P.; Schane, C.P.; Lewis, A.N.; Valdez, E.; Marada, V.V.V.R.; Hager, M.V.; Montgomery, W.; Wolf, S.; Schreiber, K.; Schreiber, H.; Bailey, K.; Fan, T.M.; Hergenrother, P.J.; Roy, E.J.; Kranz, D.M. Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. Journal for ImmunoTherapy of Cancer 2023, 11 (5), e006509. DOI: 10.1136/jitc-2022-006509. UIUC News Bureau story at: https://news.illinois.edu/view/6367/1938908123; Illinois Newsroom Public Media story at: https://ipmnewsroom.org/immune-system-could-fight-solid-tumors/
Ranoa, D. R. E.; Holland, R. L.; Alnaji, F. G.; Green, K. J.; Wang, L.; Fredrickson, R. L.; Wang, T.; Wong, G. N.; Uelmen, J.; Maslov, S.; et al. Mitigation of SARS-CoV-2 transmission at a large public university. Nature Communications 2022, 13 (1), 3207. DOI: 10.1038/s41467-022-30833-3. UIUC News Bureau story at: https://news.illinois.edu/view/6367/148267842 ; BTN COVID-19 documentary 'The New Normal' at https://news.illinois.edu/view/6367/1325414811 ; C&EN article at: https://cen.acs.org/biological-chemistry/infectious-disease/one-univers…
Ranoa, D. R. E.; Widau, R. C.; Mallon, S.; Parekh, A. D.; Nicolae, C. M.; Huang, X.; Bolt, M. J.; Arina, A.; Parry, R.; Kron, S. J.; et al. STING Promotes Homeostasis via Regulation of Cell Proliferation and Chromosomal Stability. Cancer Research 2019, 79 (7), 1465-1479. DOI: 10.1158/0008-5472.CAN-18-1972. Featured in Cancer Research Highlights: https://aacrjournals.org/cancerres/article/79/7/1295/640495/Homeostatic….
Ranoa, D. R.E.; Parekh, A. D.; Pitroda, S. P.; Huang, X.; Darga, T.; Wong, A. C.; Huang, L.; Andrade, J.; Staley, J. P.; Satoh, T.; et al. Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs. Oncotarget 2016, 7 (18), 26496-26515. DOI: 10.18632/oncotarget.8420
Recent Publications
Ranoa, D.R.E.; Sharma, P.; Schane, C.P.; Lewis, A.N.; Valdez, E.; Marada, V.V.V.R.; Hager, M.V.; Montgomery, W.; Wolf, S.; Schreiber, K.; Schreiber, H.; Bailey, K.; Fan, T.M.; Hergenrother, P.J.; Roy, E.J.; Kranz, D.M. Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model. Journal for ImmunoTherapy of Cancer 2023, 11 (5), e006509. DOI: 10.1136/jitc-2022-006509.
Ranoa, D. R. E.; Holland, R. L.; Alnaji, F. G.; Green, K. J.; Wang, L.; Fredrickson, R. L.; Wang, T.; Wong, G. N.; Uelmen, J.; Maslov, S.; et al. Mitigation of SARS-CoV-2 transmission at a large public university. Nature Communications 2022, 13 (1), 3207. DOI: 10.1038/s41467-022-30833-3.
Tee, M. L.; Ubial, P. J. R.; Ranoa, D. R. E.; Tee, C. A.; Abrilla, A. A.; Trinidad, L. J. P. L.; Chiong, C. M.; Berba, R. P.; Carrillo, R. J. D.; Lim, M. C. F. Direct saliva versus conventional nasopharyngeal swab qRT-PCR to diagnose SARS–CoV2: Validity study. Asian J. Res. Infect. Dis 2021, 6, 37-46.
Zheng, W.; Ranoa, D. R. E.; Huang, X.; Hou, Y.; Yang, K.; Poli, E. C.; Beckett, M. A.; Fu, Y.-X.; Weichselbaum, R. R. RIG-I–Like Receptor LGP2 Is Required for Tumor Control by Radiotherapy. Cancer Research 2020, 80 (24), 5633-5641. DOI: 10.1158/0008-5472.CAN-20-2324.
Ranoa, D. R. E.; Holland, R. L.; Alnaji, F. G.; Green, K. J.; Wang, L.; Brooke, C. B.; Burke, M. D.; Fan, T. M.; Hergenrother, P. J. Saliva-Based Molecular Testing for SARS-CoV-2 that Bypasses RNA Extraction. bioRxiv 2020, 2020.2006.2018.159434. DOI: 10.1101/2020.06.18.159434.
Kim, S. M.; DeFazio, J. R.; Hyoju, S. K.; Sangani, K.; Keskey, R.; Krezalek, M. A.; Khodarev, N. N.; Sangwan, N.; Christley, S.; Harris, K. G.; Malik, A.; Zaborin,A., Bouziat, R.; Ranoa, D.R.E.; Wiegerinck, M.; Ernest, J.D.; Shakhsheer, B.A.; Fleming, I.D.; Weichselbaum, R.R.; Antonopoulos, D.A.; Gilbert, J.A.; Barreiro, L.B.; Zaborina, O.; Jabri, B.; Alverdy, J.C. Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity. Nature Communications 2020, 11 (1), 2354. DOI: 10.1038/s41467-020-15545-w.
Szymura, S. J.; Bernal, G. M.; Wu, L.; Zhang, Z.; Crawley, C. D.; Voce, D. J.; Campbell, P.-A.; Ranoa, D.R.E.; Weichselbaum, R. R.; Yamini, B. DDX39B interacts with the pattern recognition receptor pathway to inhibit NF-κB and sensitize to alkylating chemotherapy. BMC Biology 2020, 18 (1), 32. DOI: 10.1186/s12915-020-0764-z.
Ranoa, D. R. E.; Widau, R. C.; Mallon, S.; Parekh, A. D.; Nicolae, C. M.; Huang, X.; Bolt, M. J.; Arina, A.; Parry, R.; Kron, S. J.; et al. STING Promotes Homeostasis via Regulation of Cell Proliferation and Chromosomal Stability. Cancer Research 2019, 79 (7), 1465-1479. DOI: 10.1158/0008-5472.CAN-18-1972.
Ranoa, D. R.E.; Parekh, A. D.; Pitroda, S. P.; Huang, X.; Darga, T.; Wong, A. C.; Huang, L.; Andrade, J.; Staley, J. P.; Satoh, T.; et al. Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs. Oncotarget 2016, 7 (18), 26496-26515. DOI: 10.18632/oncotarget.8420
Mattis, D. M.; Chervin, A. S.; Ranoa, D. R. E.; Kelley, S. L.; Tapping, R. I.; Kranz, D. M. Studies of the TLR4-associated protein MD-2 using yeast-display and mutational analyses. Molecular immunology 2015, 68 (2), 203-212.
Ranoa, D. R. E.; Kelley, S. L.; Tapping, R. I. Human lipopolysaccharide-binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to Toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex. Journal of Biological Chemistry 2013, 288 (14), 9729-9741.
Guan, Y.; Ranoa, D. R. E.; Jiang, S.; Mutha, S. K.; Li, X.; Baudry, J.; Tapping, R. I. Human TLRs 10 and 1 Share Common Mechanisms of Innate Immune Sensing but Not Signaling. The Journal of Immunology 2010, 184 (9), 5094. DOI: 10.4049/jimmunol.0901888.
