DR. ZHAOHUI WANG'S LABORATORY


ABOUT DR. ZHAOHUI WANG


Dr. Zhaohui Wang is an Assistant Professor and the Director of Precision Medicine at the Terasaki Institute for Biomedical Innovation (TIBI). He also serves as an adjunct assistant professor at Duke University. Dr. Wang earned his Ph.D. in Biochemistry and Molecular Biology from the Beijing Institute of Genomics, Chinese Academy of Sciences, where he discovered Matrine, a novel autophagy inhibitor with potential synergistic effects for cancer treatment.

Following his Ph.D., Dr. Wang completed his postdoctoral training at the Duke Brain Tumor Center. There, he characterized TERT promoter mutations in a large cohort of cancer patients, confirming the positive correlation between TERT promoter hotspot mutations and telomerase activation in adult gliomas. His research also uncovered the gain-of-function of PPM1D mutations in brainstem gliomas, leading to the identification of a promising combination therapy with PARP inhibitors for PPM1D-mutant brainstem gliomas. This type of brain tumor predominantly affects children and previously had no effective treatment options available.

After his postdoctoral training, Dr. Wang took on the role of Executive Director at the Duke Woo Center for Big Data and Precision Health. Driven by the challenges of developing preclinical animal models for pediatric brain tumors and IDH-mutant gliomas, he shifted his focus to developing next-generation organoid models to overcome the limitations of traditional animal models and conventional organoid culture. At the center, he led a multidisciplinary team to invent Micro-OrganoSphere (MOS) technology, a rapid and high-throughput organoid culture approach that enhances precision oncology and various applications using normal tissue-derived organoids. Additionally, he spearheaded efforts to leverage machine learning and big data, adopting a multidisciplinary approach to bridge the gap between AI, imaging science, healthcare data, and clinical domain knowledge. This initiative supported research projects, educational experiences, and entrepreneurship opportunities for Duke faculty and students in collaboration with clinical and industry partners worldwide.

Dr. Wang was subsequently invited to join a spin-off company that licensed the MOS technology. There, he spearheaded early research efforts, diagnostic assay development, and partnerships with top academic institutions, pharmaceutical, and biotech companies.

Equipped with extensive experience from both academia and industry, Dr. Wang is committed to finding more effective and less toxic cancer treatments. His lab at TIBI focuses on precision medicine, brain tumors, stem cells, tissue regeneration, and the development of next-generation organoid technology. His dedication to advancing biomedical innovation makes his lab an exciting and dynamic environment for researchers passionate about transforming patient care.


RESEARCH OVERVIEW


Dr. Wang's laboratory is dedicated to advancing organoid technology and disease modeling to enhance our understanding of stem cell biology and develop novel cancer treatments, particularly for gliomas. Our research integrates innovative ex vivo models, AI-enhanced phenotypic screening, biomaterials, and biosensors to address three main objectives in precision medicine:


Next-Generation Patient Avatars for Precision Oncology and Drug Discovery


By leveraging our advanced organoid and organ-on-a-chip technologies, we aim to revolutionize personalized medicine through the creation of physiologically relevant, patient-specific avatars. These avatars are crucial for understanding the biology of cancer and serve as the cornerstone for developing novel treatments and advancing personalized medicine.


Brain Tumor Research


Our lab aims to overcome the challenges of brain tumor research by establishing physiologically relevant ex vivo brain tumor models, particularly for cases where preclinical animal models are difficult to develop, such as pediatric brain tumors and certain low-grade adult gliomas. These models will accurately replicate the tumor microenvironment and blood-brain barrier, thereby accelerating translational research and guiding treatment for glioma patients. We are especially interested in exploring cancer-neuron crosstalk in gliomagenesis. By developing a multi-organ-on-a-chip culture system integrated with biosensors and neural circuits, we aim to understand the intricate interactions between glioma cells and their surrounding neural ecosystem, uncover novel therapeutic targets, and improve treatment strategies. Ultimately, we will leverage our high-throughput AI-enhanced phenotypic screening platform to identify effective treatments for brain tumors.


Cellular Plasticity During Tissue Regeneration and Repair


Cellular plasticity is crucial for tissue homeostasis and repair, allowing differentiated cells to revert to a progenitor-like state or transdifferentiate into other cell types. This ability is vital for maintaining tissue integrity and function, especially following injury. Despite its importance, it remains unclear whether cell fate plasticity is an inherent property of predetermined subpopulations, or a stochastic process influenced by environmental cues. Understanding these principles could provide critical insights into fundamental biological processes. We will leverage both iPSC and adult stem cell organoid models and employ a multidisciplinary approach using recently developed techniques to understand the spatiotemporal aspects of cellular plasticity and stochasticity in different tissue types.


Join Our Mission


We welcome researchers, students, and collaborators who share our passion for developing cures for cancer and advancing stem cell biology. If you are driven to explore the frontiers of precision medicine and contribute to meaningful discoveries, we encourage you to join our team. Together, we can push the boundaries of science and make a lasting impact on human health.


Team Photos



Team 



Interns



Alumni



CONTACT US


For more information about our research, to discuss potential collaborations, or to inquire about joining our team, please reach out to us at zhaohui.wang@terasaki.org.


RESEARCH PAPERS


1.            Xiang K, Wang E, Mantyh J, Rupprecht G, Negrete M, Sanati G, Hsu C, Randon P, Dohlman A, Kretzschmar K WANG Z, Wang X, Clevers H, Hsu D, Shen X. Chromatin Remodeling in Patient‐Derived Colorectal Cancer Models. Advanced Science. 2024;11(16):2303379.

2.            Kawakita S, Shen A, Chao C-C, WANG Z, Cheng S, Li B, Jiang C. An integrated database of experimentally validated major histocompatibility complex epitopes for antigen-specific cancer therapy. Antibody Therapeutics. 2024:tbae011.

3.            Han Y, Shen A, WANG Z, Garrett A, Jiang C. Distinct signatures of tumor-associated macrophage subpopulations predict survival in renal cell carcinoma. Cancer Research. 2024;84(6_Supplement):3457-.

4.            WANG Z, Boretto M, Millen R, Natesh N, Reckzeh ES, Hsu C, Negrete M, Yao H, Quayle W, Heaton BE. Rapid tissue prototyping with micro-organospheres. Stem cell reports2022. p. 1959-75.

5.            Hsu C, WANG Z, Oh S, Rupprecht G, Pittman K, Smith A, Delubac D, Shen X, Jia J, Hsu SD. Microorganospheres as a novel precision oncology platform in colorectal cancer. American Society of Clinical Oncology; 2022.

6.            Ding S, Hsu C, WANG Z, Natesh NR, Millen R, Negrete M, Giroux N, Rivera GO, Dohlman A, Bose S. Patient-derived micro-organospheres enable clinical precision oncology. Cell Stem Cell. 2022;29(6):905-17. e6.

7.            WANG Z, Xu C, Diplas BH, Moure CJ, Chen C-PJ, Chen LH, Du C, Zhu H, Greer PK, Zhang L. Targeting mutant PPM1D sensitizes diffuse intrinsic pontine glioma cells to the PARP inhibitor olaparib. Molecular Cancer Research. 2020;18(7):968-80.

8.            Moure CJ, Diplas BH, Chen LH, Yang R, Pirozzi CJ, WANG Z, Spasojevic I, Waitkus MS, He Y, Yan H. CRISPR editing of mutant IDH1 R132H induces a CpG methylation-low state in patient-derived glioma models of G-CIMP. Molecular Cancer Research. 2019;17(10):2042-50.

9.            Waitkus MS, Pirozzi CJ, Moure CJ, Diplas BH, Hansen LJ, Carpenter AB, Yang R, WANG Z, Ingram BO, Karoly ED. Adaptive evolution of the GDH2 allosteric domain promotes gliomagenesis by resolving IDH1R132H-induced metabolic liabilities. Cancer research. 2018;78(1):36-50.

10.          Diplas BH, Waitkus MS, He X, Brosnan-Cashman J, Liu H, Chen L, WANG Z, Moure C, Killela P, Lipp ES. GENE-01. THE GENOMIC LANDSCAPE OF TRIPLE-NEGATIVE GLIOBLASTOMA. Neuro-Oncology. 2018;20(suppl_6):vi102-vi3.

11.          Diplas BH, He X, Brosnan-Cashman JA, Liu H, Chen LH, WANG Z, Moure CJ, Killela PJ, Loriaux DB, Lipp ES. The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma. Nature communications. 2018;9(1):2087.

12.          Diplas B, Waitkus M, He X, Brosnan-Cashman J, Liu H, Chen L, WANG Z, Moure C, Killela P, Lipp E. GENE-42. THE GENOMIC LANDSCAPE OF TRIPLE-NEGATIVE GLIOBLASTOMA. Neuro-Oncology. 2018;20(suppl_6):vi112-vi.

13.          Xu C, Liu X, Geng Y, Bai Q, Pan C, Sun Y, Chen X, Yu H, Wu Y, Zhang P, WANG Z, Yang R, Lewis J, Bigner D, Zhao F, He Y, Yan H, Shen Q, Zhang L. Patient-derived DIPG cells preserve stem-like characteristics and generate orthotopic tumors. Oncotarget. 2017;8(44):76644.

14.          Chen X, Zhu Y, WANG Z, Zhu H, Pan Q, Su S, Dong Y, Li L, Zhang H, Wu L. mTORC1 alters the expression of glycolytic genes by regulating KPNA2 abundances. Journal of proteomics. 2016;136:13-24.

15.          Huang D-S, WANG Z, He X-J, Diplas BH, Yang R, Killela PJ, Meng Q, Ye Z-Y, Wang W, Jiang X-T. Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation. European Journal of Cancer. 2015;51(8):969-76.

16.          Zhang L, Chen LH, Wan H, Yang R, WANG Z, Feng J, Yang S, Jones S, Wang S, Zhou W. Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas. Nature genetics. 2014;46(7):726-30.

17.          Killela PJ, Pirozzi CJ, Healy P, Reitman ZJ, Lipp E, Rasheed BA, Yang R, Diplas BH, WANG Z, Greer PK. Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget. 2014;5(6):1515.

18.          WANG Z, Zhang J, Wang Y, Xing R, Yi C, Zhu H, Chen X, Guo J, Guo W, Li W. Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases. Carcinogenesis. 2013;34(1):128-38.

19.          Xing R, Li W, Cui J, Zhang J, Kang B, Wang Y, WANG Z, Liu S, Lu Y. Gastrokine 1 induces senescence through p16/Rb pathway activation in gastric cancer cells. Gut. 2012;61(1):43-52.

20.          Wang Y, Wei H, Pan Q, WANG Z, Xing R, Li W, Zhang J, Ding M, Guo J, Wu L. Identification and elimination of heterophilic antibody interference during antibody pair screening. Analytical biochemistry. 2012;430(1):1-3.

Patents:

1.            WANG Z, Shen X. Methods and apparatuses for purification of gel droplets supporting biological tissue. US Patent App. 18/126,393; 2023.

2.            Shen X, Hsu D, Motschman J, Delubac D, WANG Z. Methods and apparatuses for patient-derived micro-organospheres. US Patent 11,555,180; 2023.

3.            Shen X, Delubac D, Hsu D, Motschman J, WANG Z. Precision drug screening for personalized cancer therapy. US Patent App. 17/178,210; 2021.

4.            WANG Z, Shen X. Methods and apparatuses for testing hepatocyte toxicity using microorganospheres. Application PCT/US2023/066409, 2023

5.             Shen X, WANG Z, Quayle, W, Jenkinson G. Imaging-based microorganosphere drug assays. Application US18/235, 2023