(6s) Metabolic Sugar Labeling for Cancer Targeting and Immunoengineering

Title: Metabolic Sugar Labeling for Cancer Targeting
and Immunoengineering

Hua Wang, David
J. Mooney

Harvard
John A. Paulson School of Engineering and Applied Sciences, Wyss Institute for
Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138,
USA.

Abstract: Cancer
is still one of the leading causes of human deaths worldwide, and the
development of effective and safe cancer therapies remains a significant
challenge. One of my general interest in the field of cancer research is to
understand how cancer cells and immune cells can be manipulated or engineered
to improve and innovate cancer therapies. For example, cancer cells can
actively metabolize unnatural monosaccharides bearing functional groups and
express them on the cell surface in the form of glycoproteins. The cell-surface
chemical tags, coupled with efficient Click chemistries, allow for conjugation
of molecules of interest to monitor or manipulate cancer cells. Similarly,
unnatural sugars can be utilized to metabolically label and regulate immune
cells. I have been exploring how metabolic labeling and targeted modulation of
tumor cells and immune cells can be utilized to develop potent cancer
therapies. Immune responses involved in tissue repair and biomedical
implant has proven critical, and efforts have been made to steer these immune responses towards
promoting tissue regeneration. I am interested
in understanding the role of T cells, dendritic cells, and neutrophils in
tissue regeneration, and utilizing biomaterials to modulate these immune cells in
situ to regulate tissue repair.

Research Interests:

1. Metabolic Labeling and Targeting of Cancer
Cells and Immune Cells

2. Cancer Immunotherapy

3. Immunoengineering for Regenerative Medicines

4. Polymer Chemistry and Macromolecular Materials

Teaching Interests: Core undergraduate and graduate courses in Bioengineering/Chemical engineering/Materials
Science/Chemistry. Courses that I have experience in teaching include Polymer chemistry,
Biomaterials, Immunoengineering, Cancer biology.

Representative Publications:

1.   Wang, H., Sobral, M., Cartwright, A., Zhang,
D., Li, A., Dellacherie, M., Koshy, S., Wucherpfennig, K., Mooney, D. In Vivo
Metabolic Labeling and Targeted Modulation of Dendritic Cells. Nat.
Biotechnol. 2019, under revision.

2.   Wang, H., 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, under revision.

3.   Wang, H., Najibi, A., Sobral, M., Li, A.,
Verbeke, C., Mooney, D. Antigen-Free Cancer Vaccine to Treat Poorly Immunogenic
Tumors. Nat. Commun. 2019, under revision.

4.   Wang, H., Mooney, D. Biomaterial-Assisted
Targeted Modulation of Immune Cells in Cancer Treatment. Nat. Mater. 2018, 17, 761-772.

5.   Wang, H., Wang, R., Cai K., He H., Liu, Y.,
Yen, J., Wang, Z., Xu, M., Sun, Y., Zhou, X., Yin, Q., Tang, L., Wang, Z.,
Dobrucka, I.T., Dobrucki, L.W., Chaney, E.J., Boppart, S.A., Fan, T.M., Yin,
L., Lezmi, S., Chen, X., Yin, L., Cheng, J. Selective In Vivo Cell Labeling Mediated
Cancer Targeting. Nat. Chem. Biol. 2017, 13, 415-424.

6.   Wang, H., Tang, L., Liu, Y., Dobrucka, I.T.,
Dobrucki, L.W., Yin, L., Cheng, J. In Vivo Targeting of Metabolically Labeled
Cancers with Ultra-Small Silica Nanoconjugates. Theranostics 2016, 6, 1467-1476.

7.   Wang, H., Gauthier, M., Kelly, J. R.,
Miller, R.J., Xu, M., O’Brien, W.D., Cheng, J. Targeted Ultrasound Assisted
Cancer-Selective Labeling and Imaging. Angew.
Chem. Int. Ed. 2016, 128, 1-6.

8.   Wang, H., Xu, M., Xiong, M., Cheng, J. Reduction-Responsive
Dithiomaleimide-Based Nanomedicine with High Drug Loading and FRET-Indicated
Drug Release. Chem. Commun. 2015, 51, 4807-4810.

9.   Wang, H., Tang, L., Tu, C., Song, Z., Yin,
Q., Yin, L., Zhang, Z., Cheng, J. Redox-Responsive, Core-Cross-Linked Micelles
Capable of On-Demand, Concurrent Drug Release and Structure Disassembly. Biomacromolecules 2013, 14, 3706-3712.