Research | Pun Lab

Our research focuses on advancing macromolecule drug delivery technology by developing new materials. We are actively working in the following application areas:

1. Cancer Therapy

Over 12 million people in the U.S. are currently battling cancer. Cytotoxic chemotherapy remains the preferred frontline strategy used against most types of cancer. While effective, treatment-related side effects such as major organ damage, infertility, immunosuppression, and nausea/vomiting severely compromise patient quality of life. We are developing technologies for improved detection and treatment of cancer.

Ongoing projects in this area include:

Synthetic materials for adoptive T cell therapy. T cell immunotherapy demonstrates remarkable anti-cancer activity in the clinic. We are working to develop materials that improve the manufacturing and in vivo performance of T cell therapies.
Polymers for drug delivery. With Dr. Patrick Stayton, we are synthesizing polymeric drug carriers to change the biodistribution of small molecule drugs for immunotherapy, thereby reducing toxicity.
Cancer vaccine delivery. Cancer vaccines are a promising inmuno-oncology approach that can elicit anti-cancer protection from the immune system. Together with Dr. Patrick Stayton and Dr. Nora Disis, we are developing polymer-based carriers that can be recognized by and activate dendritic cells for antigen presentation, leading to cancer prevention and therapy.

Selected recent publications:

Heinze, C.M.*, Pichon, T.J.*, Wu, A.Y., Baldwin, M., Matthaei, J., Song, K., Sylvestre, M., Gustafson, J., White, N.J., Jensen, M.C. and Pun, S.H. Spatial Control of CAR T Cell Activation Using Tumor-Homing Polymers. Journal of the American Chemical Society 2025, v147(6), 5149-5161.
Nguyen, D.C.*, Song, K.*, Jokonya, S., Yazdani, O., Sellers, D.L., Wang, Y., Zakaria, A., Pun, S.H., and Stayton, P.S. Mannosylated STING agonist ‘drugamers’ for dendritic cell-mediated cancer immunotherapy. ACS Central Science 2024, 10(3), 666–675.
Olshefsky, A., Benasutti, H., Sylvestre, M., Butterfield, G.L., Rocklin, G.J., Richardson, C., Hicks, D.R., Lajoie, M.J., Song, K., Leaf, E., Treichel, C., Decarreau, J., Ke, S., Kher, G., Carter, L., Chamberlain, J.S., Baker, D., King, N.P., and Pun, S.H. In vivo selection of synthetic nucleocapsids for tissue targeting. PNAS 2023, 120(46), e2306129120.
Lv, S.*, Song, K.*, Yen, A., Peeler, D.J., Nguyen, D.C., Olshefsky, A., Sylvestre, M., Srinivasan, S., Stayton, P.S., and Pun, S.H. Well-defined mannosylated polymer for peptide vaccine delivery with enhanced antitumor immunity. Advanced Healthcare Materials 2022, 11(9), 2101651.
Kacherovsky, N.*, Cardle, I.I.*, Cheng, E.L., Yu, J.L., Baldwin, M.L., Salipante, S.J., Jensen, M.C., and Pun, S.H. Traceless aptamer-mediated isolation of CD8+ T cells for chimeric antigen receptor T-cell therapy. Nature Biomedical Engineering 2019, 3, 783-795.

We are grateful to the following current and past funding sources: NIH NCI, NIH NIBIB, NSF DMR, Alliance for Cancer Gene Therapy, Washington Research Foundation.

2. Materials for Trauma Medicine

Traumatic injuries are the leading cause of death for the 1 to 46 age group in the United States. With Dr. Nathan White (UW Emergency Medicine), we are developing new biomaterials for treatment of trauma victim, including injectable hemostatic materials, multifunctional wound bandages, and low volume resuscitants. This work has been featured on the AAAS Science Update podcast and UWTV. This work is conducted as part of the RESCU (Resuscitation Engineering Science Unit) at the University of Washington.

Selected recent publications:

Pichon, T.J., Wang, X., Mickelson, E.E., Huang, W.C., Hilburg, S.L., Stucky, S., Ling, M., St. John, A.E., Ringgold, K.W., Snyder, J.M., Pozzo, L.D., Lu, M., White, N.J., and Pun, S.H. Engineering low volume resuscitants for the prehospital care of severe hemorrhagic shock. Angewandte Chemie 2024, 63(31), e202402078.
Chan, L.W.G., Kim, C.H., Wang, X., Pun, S.H., White, N.J., and Kim, T.H. PolySTAT-modified chitosan gauzes for improved hemostasis in external hemorrhage. Acta Biomaterialia 2016, 31, 178–185.
Chan, L.W.G., Wang, X., Wei, H., Pozzo, L.D., White, N.J., and Pun, S.H. A synthetic fibrin cross-linking polymer for modulating clot properties and inducing hemostasis. Science Translational Medicine 2015, 7, 277ra29.

We are grateful to NIH NIBIB, NIH NHLBI and DOD for funding support.

3. Kidney Disease Treatment

Chronic kidney disease is a major health problem worldwide. Due to limited therapies to arrest disease advancement to kidney failure, many patients suffer high morbidity and poor five-year survival rates. In many kidney diseases, injury and loss of kidney podocytes directly underlies declining kidney function. With Dr. Stuart Shankland (UW Nephrology), we are developing polymer-based materials for targeted drug delivery to the kidney.

Selected recent publications:

Liu, G.W.*, Pippin, J.W.*, Eng, D.G., Lv, S., Shankland, S.J., and Pun, S.H. Nanoparticles exhibit greater accumulation in kidney glomeruli during experimental glomerular kidney disease. Physiological Reports 2020, 8, e14545.
Cheng, Y.*, Liu, G.W.*, Jain, R., Pippin, J.W., Shankland, S.J., and Pun, S.H. Boronic acid copolymers for direct loading and acid-triggered release of Bis-T-23 in cultured podocytes. ACS Biomaterials Science & Engineering 2018, 4, 3968–3973.
Liu, G.W.*, Prossnitz, A.N.*, Eng, D.G., Cheng, Y., Subrahmanyam, N., Pippin, J.W., Lamm, R.J., Ngambenjawong, C., Ghandehari, H., Shankland, S.J., and Pun, S.H. Glomerular disease augments kidney accumulation of synthetic anionic polymers. Biomaterials 2018, 178, 317–325.

We are grateful to the DOD PRMRP for funding support.

4. Aptamer Discovery and Engineering

Aptamers are oligonucleotide sequences capable of folding into secondary structures that bind with high affinities to target molecules. We are interested in discovering novel aptamers and developing these aptamers for biomedical applications, ranging from cell therapy manufacturing to diagnostics to targeted drug delivery.

Selected recent publications:

Cheng, E.L.*, Cardle, I.I.*, Kacherovsky, N.*, Bansia, H.*, Wang, T.*, Zhou, Y-S., Raman, J., Yen, A., Gutierrez, D., Salipante, S.J., des Georges, A., Jensen, M.C., and Pun, S.H. Discovery of a transferrin receptor 1-binding aptamer and its application in cancer cell depletion for adoptive T-cell therapy manufacturing. Journal of the American Chemical Society 2022, 144(30), 13851–13864.

Yang, L.F., Kacherovsky, N., Liang, J., Salipante, S.J., and Pun, S.H. SCORe: SARS-CoV-2 Omicron variant RBD-binding DNA aptamer for multiplexed detection and pseudovirus neutralization. Analytical Chemistry 2022, 94(37), 12683–12690.

Kacherovsky, N.*, Yang, L.F.*, Dang, H.V.*, Cheng, E.L., Cardle, I.I., Walls, A.C., McCallum, M., Sellers, D.L., DiMaio, F., Salipante, S.J., Corti, D., Veesler, D., and Pun, S.H. Discovery and characterization of spike N-terminal domain-binding aptamers for rapid SARS-CoV-2 S detection. Angewandte Chemie 2021, 133, 21381–21385.

Kacherovsky, N.*, Cardle, I.I.*, Cheng, E.L., Yu, J.L., Baldwin, M.L., Salipante, S.J., Jensen, M.C., and Pun, S.H. Traceless aptamer-mediated isolation of CD8+ T cells for chimeric antigen receptor T-cell therapy. Nature Biomedical Engineering 2019, 3, 783-795.

We are grateful to the NIH NIBIB and NIAAA for funding support.