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Zong, Hui

Hui Zong

Primary Appointment

Microbiology, Immunology, and Cancer Biology

Contact Information

PO Box 800734
Charlottesville, VA 22908
Telephone: +1 434-982-1956
Fax: +1 434-982-1071

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 ?personality?/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.

Selected Publications

Ledur PF, Liu C, He H, Harris AR, Minussi DC, Zhou HY, Shaffrey ME, Asthagiri A, Lopes MB, Schiff D, Lu YC, Mandell JW, Lenz G, Zong H, Culture conditions tailored to the cell of origin are critical for maintaining native properties and tumorigenicity of glioma cells., 2016; Neuro-oncology. 18(10) 1413-24 PMID: 27106408 | PMCID: PMC5035523

Zong H, Parada LF, Baker SJ, Cell of origin for malignant gliomas and its implication in therapeutic development., 2015; Cold Spring Harbor perspectives in biology. 7(5) PMID: 25635044 |

Galvao RP, Kasina A, McNeill RS, Harbin JE, Foreman O, Verhaak RG, Nishiyama A, Miller CR, Zong H, Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process., 2014; Proceedings of the National Academy of Sciences of the United States of America. 111(40) E4214-23 PMID: 25246577 | PMCID: PMC4210043

Galv?o RP, Zong H, Inflammation and Gliomagenesis: Bi-Directional Communication at Early and Late Stages of Tumor Progression., 2013; Current pathobiology reports. 1(1) 19-28 PMID: 23538742 | PMCID: PMC3607461

Henner A, Ventura PB, Jiang Y, Zong H, MADM-ML, a mouse genetic mosaic system with increased clonal efficiency., 2013; PloS one. 8(10) e77672 PMID: 24143253 | PMCID: PMC3797059

Zong H, Verhaak RG, Canolk P, The cellular origin for malignant glioma and prospects for clinical advancements., 2012; Expert review of molecular diagnostics. 12(4) 383-94 PMID: 22616703 | PMCID: PMC3368274

Tasic B, Miyamichi K, Hippenmeyer S, Dani VS, Zeng H, Joo W, Zong H, Chen-Tsai Y, Luo L, Extensions of MADM (mosaic analysis with double markers) in mice., 2012; PloS one. 7(3) e33332 PMID: 22479386 | PMCID: PMC3314016

Liu C, Sage JC, Miller MR, Verhaak RG, Hippenmeyer S, Vogel H, Foreman O, Bronson RT, Nishiyama A, Luo L, Zong H, Mosaic analysis with double markers reveals tumor cell of origin in glioma., 2011; Cell. 146(2) 209-21 PMID: 21737130 | PMCID: PMC3143261

Foo LC, Allen NJ, Bushong EA, Ventura PB, Chung WS, Zhou L, Cahoy JD, Daneman R, Zong H, Ellisman MH, Barres BA, Development of a method for the purification and culture of rodent astrocytes., 2011; Neuron. 71(5) 799-811 PMID: 21903074 | PMCID: PMC3172573

Muzumdar MD, Luo L, Zong H, Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM)., 2007; Proceedings of the National Academy of Sciences of the United States of America. 104(11) 4495-500 PMID: 17360552 | PMCID: PMC1810340

Zong H, Espinosa JS, Su HH, Muzumdar MD, Luo L, Mosaic analysis with double markers in mice., 2005; Cell. 121(3) 479-92 PMID: 15882628 |