Hui Zong

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Primary Appointment

Professor, Microbiology, Immunology, and Cancer Biology

Education

  • PhD, Molecular Biology; Cellular Biology, Indiana University-Purdue University Indianapolis

Research Disciplines

Biotechnology, Cancer Biology, Cell and Developmental Biology, Development, Stem Cells & Regeneration, Genetics, Neuroimmunology, Neuroscience

Research Interests

Early detection, cancer prevention, and tumor microenvironment

Research Description

To treat cancer effectively, great efforts have been devoted to molecularly targeted therapy. While there have been great examples of success, cancer cells often develop drug resistance to evade therapy. To increase the efficacy of cancer therapy, our lab uses a mouse genetic mosaic model termed MADM to study how tumor cells attack in vivo from the tumor-initiating stage and at the single-cell resolution.
The cell of origin for cancer.
Since each cell types in our body have their unique âpersonalityâ/signaling context, they often respond to the same genetic mutations in entirely different fashion. Using a MADM glioma model, we have successfully identified oligodendrocyte precursor cells (OPCs) as the cell of origin, while other brain cell types fail to transform by the same set of mutations. We are currently investigate the unique signaling properties of OPCs to develop novel prevention/treatment strategies.
Cancer prevention.
Through careful analysis, we found that mutant OPCs massively outcompete WT OPCs long before malignancy. Such competitiveness readily explains the clinical observation of unstoppable progression of low grade glioma. This finding prompts us to look into novel strategies for glioma prevention. Using genetic tricks, we introduced competitive yet non-transforming cells to remove the competitive edge of mutant OPCs, and found that glioma is completely prevented. Excited by this proof-of-principle finding, we plan to dive deeply into the molecular mechanisms of OPC competition and to discover small-molecule compounds that can prevent glioma progression.
Tumor microenvironment (TME).
Tumor cells are never alone, and their interactions with TME cells play critical roles for tumor initiation and progression. Using a MADM model for medulloblastoma, we found that tumor cells can trans-differentiate into a distinct cell type. After validating the human relevance of our finding, we further demonstrated that tumor-derived TME cells can not only directly support tumor cells, but also activate a second type of TME cells to support tumor progression. Overall, our work revealed an intricately organized TME network in medulloblastoma, shedding light on paradigm-shifting therapeutic strategies to cut off the external support toward tumor cells.
In summary, using high resolution analysis of time, space, and cellular relationships in cancer, we are poised to devise effective therapeutic strategies to detect, prevent, and defeat cancers.

Personal Statement

To treat cancer effectively, great efforts have been devoted to molecularly targeted therapy. While there have been great examples of success, cancer cells often develop drug resistance to evade therapy. To increase the efficacy of cancer therapy, our lab uses a mouse genetic mosaic model termed MADM to study how tumor cells attack in vivo from the tumor-initiating stage and at the single-cell resolution.
The cell of origin for cancer.
Since each cell types in our body have their unique âpersonalityâ/signaling context, they often respond to the same genetic mutations in entirely different fashion. Using a MADM glioma model, we have successfully identified oligodendrocyte precursor cells (OPCs) as the cell of origin, while other brain cell types fail to transform by the same set of mutations. We are currently investigate the unique signaling properties of OPCs to develop novel prevention/treatment strategies.
Cancer prevention.
Through careful analysis, we found that mutant OPCs massively outcompete WT OPCs long before malignancy. Such competitiveness readily explains the clinical observation of unstoppable progression of low grade glioma. This finding prompts us to look into novel strategies for glioma prevention. Using genetic tricks, we introduced competitive yet non-transforming cells to remove the competitive edge of mutant OPCs, and found that glioma is completely prevented. Excited by this proof-of-principle finding, we plan to dive deeply into the molecular mechanisms of OPC competition and to discover small-molecule compounds that can prevent glioma progression.
Tumor microenvironment (TME).
Tumor cells are never alone, and their interactions with TME cells play critical roles for tumor initiation and progression. Using a MADM model for medulloblastoma, we found that tumor cells can trans-differentiate into a distinct cell type. After validating the human relevance of our finding, we further demonstrated that tumor-derived TME cells can not only directly support tumor cells, but also activate a second type of TME cells to support tumor progression. Overall, our work revealed an intricately organized TME network in medulloblastoma, shedding light on paradigm-shifting therapeutic strategies to cut off the external support toward tumor cells.
In summary, using high resolution analysis of time, space, and cellular relationships in cancer, we are poised to devise effective therapeutic strategies to detect, prevent, and defeat cancers.

Training

  • Biotechnology Training Grant
  • Cancer Research Training in Molecular Biology
  • Predoctoral Training in Neuroscience
  • Training in Cell and Molecular Biology
  • Training in the Pharmacological Sciences

Selected Publications

2024

Abecunas, C., Kidd, A. D., Jiang, Y., Zong, H., & Fallahi-Sichani, M. (2024). Multivariate analysis of metabolic state vulnerabilities across diverse cancer contexts reveals synthetically lethal associations.. bioRxiv. doi:10.1101/2023.11.28.569098

Nguyen, Y. T. M., Sibley, L., Przanowski, P., Zhao, X. -Y., Kovacs, M., Wang, S., . . . Zong, H. (2024). Toxoplasma gondii infection supports the infiltration of T cells into brain tumors. JOURNAL OF NEUROIMMUNOLOGY, 393. doi:10.1016/j.jneuroim.2024.578402

Zeng, J., Ball, E., Zhou, X., & Zong, H. (2024). Protocol for integrating tissue clearing and light-sheet imaging to analyze cancer initiation in mosaic analysis with double markers mouse models. STAR PROTOCOLS, 5(2). doi:10.1016/j.xpro.2024.103092

Rane, A., Tate, S., Sumey, J. L., Zhong, Q., Zong, H., Purow, B., . . . Swami, N. S. (2024). Open-Top Patterned Hydrogel-Laden 3D Glioma Cell Cultures for Creation of Dynamic Chemotactic Gradients to Direct Cell Migration. ACS BIOMATERIALS SCIENCE & ENGINEERING, 10(5), 3470-3477. doi:10.1021/acsbiomaterials.4c00041

2023

Zeng, J., Singh, S., Zhou, X., Jiang, Y., Casarez, E., Atkins, K. A., . . . Zong, H. (2023). A genetic mosaic mouse model illuminates the pre-malignant progression of basal-like breast cancer. DISEASE MODELS & MECHANISMS, 16(11). doi:10.1242/dmm.050219

Zeng, J., Singh, S., Jiang, Y., Casarez, E., Atkins, K. A., Janes, K. A., & Zong, H. (2023). A genetic mosaic mouse model illuminates the pre-malignant progression of basal-like breast cancer.. bioRxiv. doi:10.1101/2023.04.25.538333

Zeng, J., Alvarez-Yela, A. C., Casarez, E., Jiang, Y., Wang, L., Kelly, B. E., . . . Zong, H. (2023). Dichotomous ovarian cancer-initiating potential of Pax8+ cells revealed by a mouse genetic mosaic model. ISCIENCE, 26(5). doi:10.1016/j.isci.2023.106742

2022

Xu, B., Kucenas, S., & Zong, H. (2022). zMADM (zebrafish mosaic analysis with double markers) for single-cell gene knockout and dual-lineage tracing. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119(9). doi:10.1073/pnas.2122529119

Li, J., Chordia, M. D., Zhang, Y., Zong, H., Pan, D., & Zuo, Z. (2022). Critical role of FPR1 in splenocyte migration into brain to worsen inflammation and ischemic brain injury in mice. THERANOSTICS, 12(7), 3024-3044. doi:10.7150/thno.57218

2021

Jecrois, E. S., Zheng, W., Bornhorst, M., Li, Y., Treisman, D. M., Muguyo, D., . . . Zhu, Y. (2021). Treatment during a developmental window prevents NF1-associated optic pathway gliomas by targeting Erk-dependent migrating glial progenitors. DEVELOPMENTAL CELL, 56(20), 2871-+. doi:10.1016/j.devcel.2021.08.004

Sutcliffe, M. D., Galvao, R. P., Wang, L., Kim, J., Rosenfeld, L. K., Singh, S., . . . Janes, K. A. (2021). Premalignant Oligodendrocyte Precursor Cells Stall in a Heterogeneous State of Replication Stress Prior to Gliomagenesis. CANCER RESEARCH, 81(7), 1868-1882. doi:10.1158/0008-5472.CAN-20-1037

Jiang, Y., Huang, Y., Luo, X., Wu, J., Zong, H., Shi, L., . . . Yang, C. (2021). Neural Stimulation In Vitro and In Vivo by Photoacoustic Nanotransducers. MATTER, 4(2). doi:10.1016/j.matt.2020.11.019

2020

Terry, T. T., Cheng, T., Mahjoub, M., & Zong, H. (2020). Mosaic Analysis with Double Markers reveals IGF1R function in granule cell progenitors during cerebellar development. DEVELOPMENTAL BIOLOGY, 465(2), 130-143. doi:10.1016/j.ydbio.2020.07.008

Gao, X., Zhang, Z., Mashimo, T., Shen, B., Nyagilo, J., Wang, H., . . . Ge, W. -P. (2020). Gliomas Interact with Non-glioma Brain Cells via Extracellular Vesicles. CELL REPORTS, 30(8), 2489-+. doi:10.1016/j.celrep.2020.01.089

Yao, M., Ventura, P. B., Jiang, Y., Rodriguez, F. J., Wang, L., Perry, J. S. A., . . . Zong, H. (2020). Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth. CELL, 180(3), 502-+. doi:10.1016/j.cell.2019.12.024

2019

Ohka, F., Shinjo, K., Deguchi, S., Matsui, Y., Okuno, Y., Katsushima, K., . . . Kondo, Y. (2019). Pathogenic Epigenetic Consequences of Genetic Alterations in IDH-Wild-Type Diffuse Astrocytic Gliomas. CANCER RESEARCH, 79(19), 4814-4827. doi:10.1158/0008-5472.CAN-19-1272

Singh, S., Wang, L., Schaff, D. L., Sutcliffe, M. D., Koeppel, A. F., Kim, J., . . . Janes, K. A. (2019). In situ 10-cell RNA sequencing in tissue and tumor biopsy samples. SCIENTIFIC REPORTS, 9. doi:10.1038/s41598-019-41235-9

2018

Gonzalez, P. P., Kim, J., Galvao, R. P., Cruickshanks, N., Abounader, R., & Zong, H. (2018). p53 and NF 1 loss plays distinct but complementary roles in glioma initiation and progression. GLIA, 66(5), 999-1015. doi:10.1002/glia.23297

2017

Ledur, P. F., Onzi, G. R., Zong, H., & Lenz, G. (2017). Culture conditions defining glioblastoma cells behavior: what is the impact for novel discoveries?. ONCOTARGET, 8(40), 69185-69197. doi:10.18632/oncotarget.20193

Deguchi, S., Katsushima, K., Hatanaka, A., Shinjo, K., Ohka, F., Wakabayashi, T., . . . Kondo, Y. (2017). Oncogenic effects of evolutionarily conserved noncoding RNA ECONEXIN on gliomagenesis. ONCOGENE, 36(32), 4629-4640. doi:10.1038/onc.2017.88

Zhang, G., Xie, Y., Zhou, Y., Xiang, C., Chen, L., Zhang, C., . . . Liu, G. (2017). p53 pathway is involved in cell competition during mouse embryogenesis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114(3), 498-503. doi:10.1073/pnas.1617414114

2016

Ledur, P. F., Liu, C., He, H., Harris, A. R., Minussi, D. C., Zhou, H. -Y., . . . Zong, H. (2016). Culture conditions tailored to the cell of origin are critical for maintaining native properties and tumorigenicity of glioma cells. NEURO-ONCOLOGY, 18(10), 1413-1424. doi:10.1093/neuonc/now062

Riccio, P., Cebrian, C., Zong, H., Hippenmeyer, S., & Costantini, F. (2016). Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis. PLOS BIOLOGY, 14(2). doi:10.1371/journal.pbio.1002382

Gutierrez, F., Dou, D., Fickas, S., Wimalasuriya, D., & Zong, H. (2016). A hybrid ontology-based information extraction system. JOURNAL OF INFORMATION SCIENCE, 42(6), 798-820. doi:10.1177/0165551515610989

2015

He, H., Yao, M., Zhang, W., Tao, B., Liu, F., Li, S., . . . Lu, Y. (2016). MEK2 is a prognostic marker and potential chemo-sensitizing target for glioma patients undergoing temozolomide treatment. CELLULAR & MOLECULAR IMMUNOLOGY, 13(5), 658-668. doi:10.1038/cmi.2015.46

Zong, H., Parada, L. F., & Baker, S. J. (2015). Cell of Origin for Malignant Gliomas and Its Implication in Therapeutic Development. COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 7(5). doi:10.1101/cshperspect.a020610

2014

Galvao, R. P., Kasina, A., McNeill, R. S., Harbin, J. E., Foreman, O., Verhaak, R. G. W., . . . Zong, H. (2014). Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(40), E4214-E4223. doi:10.1073/pnas.1414389111

Zong, H. (2014). Generation and Applications of MADM-Based Mouse Genetic Mosaic System. MOUSE GENETICS: METHODS AND PROTOCOLS, 1194, 187-201. doi:10.1007/978-1-4939-1215-5_10

2013

Packard, A., Georgas, K., Michos, O., Riccio, P., Cebrian, C., Combes, A. N., . . . Costantini, F. (2013). Luminal Mitosis Drives Epithelial Cell Dispersal within the Branching Ureteric Bud. DEVELOPMENTAL CELL, 27(3), 319-330. doi:10.1016/j.devcel.2013.09.001

Galvão, R. P., & Zong, H. (2013). Inflammation and Gliomagenesis: Bi-Directional Communication at Early and Late Stages of Tumor Progression.. Current pathobiology reports, 1(1), 19-28. doi:10.1007/s40139-012-0006-3

Gay, L., Miller, M. R., Ventura, P. B., Devasthali, V., Vue, Z., Thompson, H. L., . . . Doe, C. Q. (2013). Mouse TU tagging: a chemical/genetic intersectional method for purifying cell type-specific nascent RNA. GENES & DEVELOPMENT, 27(1), 98-115. doi:10.1101/gad.205278.112

Henner, A., Ventura, P. B., Jiang, Y., & Zong, H. (2013). MADM-ML, a Mouse Genetic Mosaic System with Increased Clonal Efficiency. PLOS ONE, 8(10). doi:10.1371/journal.pone.0077672

2012

Tasic, B., Miyamichi, K., Hippenmeyer, S., Dani, V. S., Zeng, H., Joo, W., . . . Luo, L. (n.d.). Correction: Extensions of MADM (Mosaic Analysis with Double Markers) in Mice. PLoS ONE, 7(7). doi:10.1371/annotation/e4275a34-48e1-42b8-8615-f59aacaf3733

Liu, C., & Zong, H. (2012). Developmental origins of brain tumors. CURRENT OPINION IN NEUROBIOLOGY, 22(5), 844-849. doi:10.1016/j.conb.2012.04.012

Zong, H., Verhaak, R. G. W., & Canoll, P. (2012). The cellular origin for malignant glioma and prospects for clinical advancements. EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, 12(4), 383-394. doi:10.1586/ERM.12.30

Tasic, B., Miyamichi, K., Hippenmeyer, S., Dani, V. S., Zeng, H., Joo, W., . . . Luo, L. (2012). Extensions of MADM (Mosaic Analysis with Double Markers) in Mice. PLOS ONE, 7(3). doi:10.1371/journal.pone.0033332

2011

Foo, L. C., Allen, N. J., Bushong, E. A., Ventura, P. B., Chung, W. -S., Zhou, L., . . . Barres, B. A. (2011). Development of a Method for the Purification and Culture of Rodent Astrocytes. NEURON, 71(5), 799-811. doi:10.1016/j.neuron.2011.07.022

Papagiannakopoulos, T., Friedmann-Morvinski, D., Neveu, P., Dugas, J. C., Gill, R. M., Huillard, E., . . . Kosik, K. S. (2012). Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases. ONCOGENE, 31(15), 1884-1895. doi:10.1038/onc.2011.380

Liu, C., Sage, J. C., Miller, M. R., Verhaak, R. G. W., Hippenmeyer, S., Vogel, H., . . . Zong, H. (2011). Mosaic Analysis with Double Markers Reveals Tumor Cell of Origin in Glioma. CELL, 146(2), 209-221. doi:10.1016/j.cell.2011.06.014

Tasic, B., Hippenmeyer, S., Wang, C., Gamboa, M., Zong, H., Chen-Tsai, Y., & Luo, L. (2011). Site-specific integrase-mediated transgenesis in mice via pronuclear injection. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108(19), 7902-7907. doi:10.1073/pnas.1019507108

2010

Hippenmeyer, S., Youn, Y. H., Moon, H. M., Miyamichi, K., Zong, H., Wynshaw-Boris, A., & Luo, L. (2010). Genetic Mosaic Dissection of Lis1 and Ndel1 in Neuronal Migration. NEURON, 68(4), 695-709. doi:10.1016/j.neuron.2010.09.027