Our laboratory aims to understand how cells can be manipulated and engineered to facilitate targeted delivery of therapeutics and regulate intercellular interactions, in order to improve and innovate therapies for cancers, injured tissues, autoimmune disorders, and other diseases. In one path towards this goal, we utilize chemistry, chemical biology, and synthetic biology tools to modify or engineer cells for subsequent tracking and targeted modulation in vivo. In another path, we develop biomaterials that can home and manipulate immune cells in vivo, and apply them to the development of cancer vaccines, cell therapies, and medical devices. New molecules, polymers, and biomaterials that can serve as diagnostics, therapeutics, and medical supplies/devices are also of our interest.
1. Therapeutic Cancer Vaccines
We have been developing therapeutic cancer vaccines for treating various types of cancer. For now, our lab is fully developing four cancer vaccine platforms: Dendritic cell vaccines, tumor extracellular vesicle vaccines, neoantigen mRNA vaccines, and dendritic cell-homing material scaffold vaccines. The four vaccine platforms can be fabricated from hours to days to weeks, covering varied urgency of different types and stages of cancer. In one path towards the translation, we have been assessing these cancer vaccines in canine trials by collaborating with Vet Med faculty and clinicians.
Representative publications:
(1) Bhatta R, Han J, Liu Y, Bo Y, Lee D, Zhou J, Wang Y, Nelson ER, Chen Q, Zhang XS, Hassaneen W, Wang H*. Metabolic Tagging of Extracellular Vesicles and Development of Enhanced Extracellular Vesicle Based Cancer Vaccines. Nature Communications 2023, 14, 8047. [Link]
(2) Han J, Bhatta R, Liu Y, Bo Y, Elosegui-Artola A, Hua Wang*. Metabolic Glycan Labeling Immobilizes Dendritic Cell Membrane and Enhances Antitumor Efficacy of Dendritic Cell Vaccine. Nature Communications 2023, 14, 5049. [Link]
(3) Bhatta R, Han J, Liu Y, Bo Y, Wang Y, Nguyen D, Chen Q, Wang H*. Extracellular Vesicle Hydrogels with Tunable Viscoelasticity and Injectability for Depot Vaccines. Nature Communications 2025, 16, 3781. [Link]
(4) Wang H, Sobral M, Zhang D, Cartwright A, Li A, Dellacherie M, Koshy S, Wucherpfennig K, Mooney D. Metabolic Labeling and Targeted Modulation of Dendritic Cells. Nature Materials 2020, 19, 1244–1252. [Link]
(5) Wang H, Najibi A, Sobral M, Seo BR, Lee JY, Wu D, Li A, Verbeke C, Mooney D. Biomaterial-Based Scaffold for In Situ Chemo-Immunotherapy to Treat Poorly Immunogenic Tumors. Nature Communications 2020, 11, 5696. [Link]
2. Metabolic Labeling and Targeting of Cells
Cells can actively metabolize unnatural monosaccharides bearing chemical tags and express them in the form of glycoproteins. These cell-surface chemical tags (e.g., azide) enable targeted conjugation of molecules of interest via efficient chemistries to monitor or modulate cells. In the context of cancer cells, we have been exploring cancer-selective labeling in vivo and subsequent development of cancer-targeted therapies. Similarly, unnatural sugars can metabolically label immune cells with chemical tags, which will be utilized for targeted modulation of dendritic cells (DCs) and T cells with immunomodulatory agents in my laboratory. We are also interested in exploring metabolic labeling, tracking, and targeting of stem cells.
Representative publications:
(1)Liu Y, Zhou J, Wang Y, Nguyen D, Baskaran D, Liu Y, Wang H. RENBP Inhibition Amplifies Metabolic Glycan Labeling Efficiency of Antigen Presenting Cells in Vitro and in Vivo. Cell Chemical Biology 2025. [Link]
(2) Bo Y, Zhou J, Cai K, Wang Y, Feng Y, Li W, Jiang Y, Kuo S, Roy J, Anorma C, Gardner SH, Luu LM, Lau GW, Bao Y, Chan J, Wang H*, Cheng J*. Leveraging Intracellular ALDH1A1 Activity for Selective Cancer Stem-like Cells Labeling and Targeted Treatment via Click Reaction. Proceedings of the National Academy of Sciences 2023, 120 (36), e2302342120. [Link]
(3) Wang H, Sobral M, Zhang D, Cartwright A, Li A, Dellacherie M, Tringides C, Koshy S, Wucherpfennig K, Mooney D. Metabolic Labeling and Targeted Modulation of Dendritic Cells. Nature Materials 2020, https://doi.org/10.1038/s41563-020-0680-1.
(4) Wang H, Wang R, Cai K, He H, Liu Y, Yen J, Wang Z, Xu M, Sun Y, Zhou X, Yin Q, Tang L, Dobrucka IT, Dobrucki LW, Chaney EJ, Boppart SA, Fan TM, Lezmi S, Chen X, Yin L, Cheng J. Selective In Vivo Cell Labeling Mediated Cancer Targeting. Nature Chemical Biology 2017, 13, 415-424.
(5) Wang H, Gauthier M, Kelly JR, Miller RJ, Xu M, O’Brien WD, Cheng J. Targeted Ultrasound Assisted Cancer-Selective Labeling and Imaging. Angewandte Chemie International Edition 2016, 55, 5452-5456.
3. Biomaterials-based Cancer Immunotherapy
Cancer immunotherapy has achieved significant progress in the past decade, but issues including off-target side effects and limited patient responses still exist. Biomaterial carriers of these therapies enable one to troubleshoot the delivery issues, amplify immunomodulatory effects, and home and manipulate immune cells in vivo. Our laboratory is particularly interested in developing biomaterials-based cancer vaccines and T cell therapies.
Representative publications:
(1) Zhou J, Liu Y, Xu W, Bhatta R, Han J, Baskaran D, Devmal S, Leal C, Wang H. Macroporous hydrogel-based mRNA cancer vaccine for in situ recruitment and modulation of dendritic cells. Acta Biomaterialia 2025. [Link]
(2) Wang H, Sobral M, Zhang D, Cartwright A, Li A, Dellacherie M, Tringides C, Koshy S, Wucherpfennig K, Mooney D. Metabolic Labeling and Targeted Modulation of Dendritic Cells. Nature Materials 2020, https://doi.org/10.1038/s41563-020-0680-1.
(3) Wang H, Mooney D. Biomaterial-Assisted Targeted Modulation of Immune Cells in Cancer Treatment. Nature Materials 2018, 17, 761-772.
4. Nanoscale and Microscale Biomaterials
Our laboratory will continue to develop advanced biomaterials including hydrogels, inorganic scaffolds, polymeric micelles, polymer-drug conjugates, and liposomes for applications of drug delivery, cell and tissue engineering, and in situ immunomodulation. One particular interest is the development and understanding of macroporous biomaterials that enable precise recruitment and modulation of immune cells in the context of cancers, regenerative medicines, and autoimmune disorders. We are also interested in bioinspired design of materials.
Representative publications:
(1) Zhou J, Liu Y, Xu W, Bhatta R, Han J, Baskaran D, Devmal S, Leal C, Wang H. Macroporous hydrogel-based mRNA cancer vaccine for in situ recruitment and modulation of dendritic cells. Acta Biomaterialia 2025. [Link]
(2) Bhatta R, Han J, Liu Y, Bo Y, Wang Y, Nguyen D, Chen Q, Wang H*. Extracellular Vesicle Hydrogels with Tunable Viscoelasticity and Injectability for Depot Vaccines. Nature Communications 2025, 16, 3781. [Link]
(3) Bhatta R, Han J, Liu Y, Bo Y, Wang H*. T Cell-Responsive Macroporous Hydrogels for In Situ T Cell Expansion and Enhanced Antitumor Efficacy. Biomaterials 2023, 293:121972.[Link]
(4) Wang H, Bo Y, Liu Y, Xu M, Cai K, Wang R, Cheng J. In Vivo Cancer Targeting via Glycopolyester Nanoparticle Mediated Metabolic Cell Labeling Followed by Click Reaction. Biomaterials 2019, 218, 119305.