Submitted/In preparation Manuscripts
*co-first authors; +corresponding authorsPark S+, Ho C, Birocchi F, Wolff AN, Bouffard AA, Kelly C, Mucci A, Leick M, Berger T, Maus MV+. "Rewiring transferrin receptor expression enhances CAR-T cell proliferative fitness", (In preparation)
Birocchi F*, Knudsen N*, Kienka T*, Schwartz J, Bi K, Parker A, Nobrega C, Escobar G, Cheng A, Bouffard A, Kelly C, Leick M, Mucci A, Suermondt, J, Rojas A, Pezeshki M, Park S, Barkal A, Elsallab M, Pope, H, Berger T, Sen D, Yates K, Manguso R, Maus MV. "Combinatorial in vivo CRISPR screens reveal SOCS1-anchored perturbations that enhance CAR-T cell function in solid tumors", Submitted
Key Publications
*co-first authors; +co-corresponding authors9. Park S+, Ho C, Wolff AN, Fan Y, Paek JH, Bouffard AA, Mucci A, Berger T, Paszek MJ, Maus MV+. "Engineering CAR-T cells to remodel the mucin-rich cancer glycocalyx", bioRxiv (2026) [Link]
"We show that nanoscale glycocalyx architecture and epitope position determine CAR-T cell recognition. We identify KLK5 as a protease that remodels the mucin-rich glycocalyx and enhances CAR-T cell engagement and antitumor activity. Engineering CAR-T cells to express KLK5 enables local remodeling of the tumor-cell surface and improves therapeutic activity across multiple tumor models and antigen targets. These findings establish the glycocalyx as an engineerable biophysical checkpoint and demonstrate that immune cells can be programmed to modify the physical environment surrounding their target antigens."
8. Park S+, Ho C, Alam F, Maus MV+ "Targeting the sweet coat: glycan-directed CAR-T cell therapies for cancer", Experimental & Molecular Medicine. Accepted (2026) [review]
"Cancer-associated glycans, glycoforms, mucins, glycolipids, and other highly glycosylated surface proteins create distinct targets for CAR-T-cell therapy, with several strategies already advancing into clinical testing. This review summarizes the preclinical and clinical landscape of glycan-directed CAR-T therapies and highlights key translational challenges, including antigen heterogeneity, epitope accessibility, persistence, and toxicity."
7. Park S*+, Paek JH*, Colville MJ, Huang LT, Struzyk PA, Neelamegham S, Maus MV+, Paszek MJ+. "Cancer cell glycocalyx thickness is a druggable physical barrier to cellular immunotherapy", bioRxiv. (2026) [Link]
"We establish cancer-cell glycocalyx thickness as a pharmacologically actionable physical phenotype and develop a SAIM-based screening platform that identifies compound- and cell-type-specific nanoscale glycocalyx remodeling. Castanospermine emerged as a strong thinning agent that reduced mucin-probe binding, increased MUC17 CAR-T-cell avidity, and enhanced CAR-T-mediated tumor control in real-time co-culture assays."
6. Park S, Ho CE, Birocchi F, Wolff AN, Bouffard AA, Kelly C, Salas-Benito D, Escobar G, Mucci A, Berger TR, Maus MV. "CAR-T cell therapy targeting cell-surface MUC17 in gastric tumors", Journal for ImmunoTherapy of Cancer (2025) [Link]
"We identified MUC17, a membrane-tethered mucin-type glycoprotein with minimal expression in normal tissues and frequent upregulation in gastric cancers, as a potential target for CAR-T therapy. We developed and validated MUC17-specific CAR-T cells incorporating a 4-1BB/CD3ζ signaling domain. In vitro assays assessed cytotoxicity, cytokine secretion, and T cell phenotypes across multiple gastric cancer cell lines, including CRISPR-mediated MUC17 knockout controls. In vivo efficacy was evaluated using NSG xenograft models."
5. Park S, Ho CE, Darnell EP, Wolff AN, Takei H, Birocchi F, Bouffard AA, Salas-Benito D, Escobar G, Leick MB, Mucci A, Berger TR, Maus MV. "Tuning CAR-T cells by targeting cancer-associated glycan in pancreatic cancer", Nature Communications (2025) [Link]
"We incorporate an additional binder targeting Tn-MUC1, termed a "glyco-bridge", into mesothelin-targeted CAR-T cells to enhance CAR-T cell-mediated killing. This bridge not only facilitates CAR-T cell infiltration and increases avidity for their target cells but also activates CAR molecules in a manner dependent on the density of the bridge-target antigens and the affinity of the antigen-binding domain. To broaden the glyco-bridge targeting range, we modified the binding domain to be composed of tandem Helix pomatia agglutinin (HPA) lectins, enabling effective recognition of Tn antigens across various cancer types. Our CAR-T cells with the HPA glyco-bridge exhibit superior cytotoxicity in cell-line and patient-derived xenograft (PDX) models of pancreatic cancer. By advancing binding strategies to penetrate the cancer glycocalyx, this approach opens new pathways for enhanced CAR-T cell efficacy in solid tumor immunotherapy."
4. Park S, Maus MV, Choi BD. "CAR-T cell therapy for the treatment of adult high-grade gliomas", NPJ Precision Oncology (2024) [review; Link]
"Treatment for malignant primary brain tumors, including glioblastoma, remains a significant challenge despite advances in therapy. CAR-T cell immunotherapy represents a promising alternative to conventional treatments. This review discusses the landscape of clinical trials for CAR-T cell therapy targeting brain tumors, highlighting key advancements like novel target antigens and combinatorial strategies designed to address tumor heterogeneity and immunosuppression, with the goal of improving outcomes for patients with these aggressive cancers."
3. Park S*, Choi S*, Shimpi AA, Estroff LA, Fischbach C+, Paszek MJ+. "Collagen mineralization decreases NK cell-mediated cytotoxicity of breast cancer cells via increased glycocalyx thickness", Advanced Materials (2024) [Link]
"Skeletal metastasis is common in patients with advanced breast cancer and often caused by immune evasion of disseminated tumor cells (DTCs). Here, a combination of synthetic bone matrix models with controlled mineral content, nanoscale optical imaging, and flow cytometry are utilized to evaluate how collagen type I mineralization affects the biochemical and biophysical properties of the tumor cell glycocalyx, a dense layer of glycosylated proteins and lipids decorating their cell surface. These results suggest that collagen mineralization upregulates mucin-type O-glycosylation and sialylation by tumor cells, which increases their glycocalyx thickness while enhancing resistance to attack by natural killer (NK) cells."
2. Park S, Colville MJ, Paek JH, Shurer CR, Singh A, Secor EJ, Sailer CJ, Huang L, Kuo JCH, Goudge MC, Su J, Kim M, DeLisa MP, Neelamegham S, Lammerding J, Zipfel WR, Fischbach C, Reesink HL, Paszek MJ. "Immunoengineering can overcome the glycocalyx armor of cancer cells", Nature Materials (2024) [Link]
*Highlight [Nature Materials] [Technology Networks]
"Cancer cell glycocalyx is a major line of defence against immune surveillance. However, how specific physical properties of the glycocalyx are regulated on a molecular level, contribute to immune evasion and may be overcome through immunoengineering must be resolved. Here we report how cancer-associated mucins and their glycosylation contribute to the nanoscale material thickness of the glycocalyx and consequently modulate the functional interactions with cytotoxic immune cells. Natural-killer-cell-mediated cytotoxicity is inversely correlated with the glycocalyx thickness of the target cells. Together, our results motivate the development of immunoengineering strategies that overcome the glycocalyx armour of cancer cells."
1. Park S, Kuo JCH, Reesink HL, Paszek MJ. "Recombinant mucin biotechnology and engineering", Advanced Drug Delivery Reviews (2023) [review; Link]
"Mucins represent a largely untapped class of polymeric building block for biomaterials, therapeutics, and other biotechnology. Because the mucin polymer backbone is genetically encoded, sequence-specific mucins with defined physical and biochemical properties can be fabricated using recombinant technologies. The pendent O-glycans of mucins are increasingly implicated in immunomodulation, suppression of pathogen virulence, and other biochemical activities. In this review, we discuss these advances, and the opportunities for engineered mucins in biomedical applications ranging from in vitro models to therapeutics."
Other Publications
16. Blumenberg V, June KB, Birocchi F, Escobar G, Graham C, Fan Y, Philipps MK, Park S, Harris D, Bouffard A, Kelly C, Elsallab M, Berger TR, Gallagher K, Leick MB, Mucci A, Maus MV. "Gene regulatory elements determine efficacy of BCMA-targeted CAR T-cell products", Journal for ImmunoTherapy of Cancer (2026)
15. Tharp K, Park S, Timblin G, Richards A, Berg J, Twells N, Riley NM, Peltan E, Shon DJ, Stevenson E, Tsui CK, Palomba F, Lefebvre AE, Soens R, Ayad N, Hoeve-Scott JT, Healy K, Digman M, Dilin A, Bertozzi C, Mahal LK, Swaney D, Cantor J, Paszek MJ, Weaver V. "The microenvironment dictates glyco-immune surveillance via HSF1-mediated metabolism", Science Advances (2026)
14. Ha Y, Kuo JCH, Paek JH, Park S, Jani P, Roh S, Paszek M, Abbott N. " Single cell spreading and deconstruction at liquid crystal interfaces", Journal of Colloid and Interface Science (2026)
13. Park S and Maus MV. "When tumor contact reshapes CAR-T cells", Journal of Experimental Medicine (2026)
12. Kuo A, Tender GS, Chow WD, Riley NM, Wen KC, Park S, Paek JH, Roberts DS, Peltan EL, Paszek MJ, Bertozzi CR. "The protease Cathepsin K can debulk the cancer glycocalyx", Journal of Biological Chemistry (2026)
11. Armstrong A, Plancke GVD, Nishiguchi S, Salas-Benito D, Bouffard AA, Gonclaves S, Kelly C, Birocchi F, Park S, Leick M, Berger T, Maus MV, Escobar G. "Ibrutinib and PD-1 blockade potentiate mesothelin-targeting CAR-T cell therapy in preclinical models of pancreatic cancer", Clinical Cancer Research (2025)
10. Knudsen NH, Escobar G, Korell F, Kienka T, Nobrega C, Aderson S, Cheng A, Zschummel M, Armstrong A, Bouffard A, Kann MC, Goncalves S, Pope HW, Pezeshki M, Rojas A, Suermondt JS, Philips M, Berger T, Park S, Salas-Benito D, Darnell E, Birocchi F, Leick M, Larson R, Doench JG, Sen D, Yates KB, Mangusso RT, Maus MV. " In vivo CRISPR screens identify key modifiers of CAR T cell function in myeloma", Nature (2025)
9. Salas-Benito D, Birocchi F, Park S, Ho C, Armstrong A, Parker A, Bouffard AA, Frank JA, Kim E, Kienka T, Graham K, Kelly C, Goncalves S, Leick MB, Escobar G, Rueda B, Berger TR, Maus MV. "Tandem CAR-T cells targeting mesothelin and MUC16 overcome tumor heterogeneity by targeting one antigen at a time", Journal for ImmunoTherapy of Cancer (2025)
8. Supper VM*, Donner H*, Birocchi F, Bratt A, Escobar G, Kann MC, Park S, Martin G, Korell F, Takei H, Parker A, Salas-Benito D, Darnell EP, Bailey SR, Kienka T, Bouffard A, Goncalves S, Choi BD, Haradhvala NJ, Maus MV, Leick MB. "Secretion of a VEGF-blocking scFv enhances CAR-T cell potency", Cancer Immunology Research (2025)
7. Jani P, Colville MJ, Park S, Ha Y, Paszek MJ+, and Abbott NL+. "Influence of the glycocalyx on the size and mechanical properties of plasma membrane-derived vesicles", Soft Matter (2025)
6. Beyrent E, Wei DT, Beacham GM, Park S, Zheng J, Paszek MJ, and Hollopeter G. "Dimerization activates the Inversin complex in C. elegans", Molecular Biology of the Cell (2024)
5. Wallace M, Fedorchak GR, Agrawal R, Gilbert RM, Patel J, Park S, Paszek MJ, Lammerding J. "The Lamin A/C Ig-fold undergoes cell density-dependent changes that alter epitope binding", Nucleus (2023)
4. Colville MJ, Park S, Singh A, Paszek MJ, Zipfel WR. "Azimuthal Beam Scanning Microscope Design and Implementation for Axial Localization with Scanning Angle Interference Microscopy", Biomedical Engineering Technologies (2022) [review]
3. Kuo JCH, Goudge MC, Metzloff AE, Huang L, Colville MJ, Park S, Zipfel WR, Paszek MJ. "Litmus-Body: A Molecularly Targeted Sensor for Cell-Surface pH Measurements", ACS Sensors (2020)
2. Colville MJ, Park S, Zipfel WR, Paszek MJ. "High-speed device synchronization in optical microscopy with an open-source hardware control platform", Scientific Reports (2019)
1. Lee H., Choi B, Kang HN, Kim H, Min A, Cha M, Ryu JY, Park S, Sohn J, Shin K, Yun M, Han JY, Shon MJ, Jeong C, Chung J, Lee S, Im S, Cho BC, Yoon T. "Profiling of protein–protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors ", Nature Biomedical Engineering (2018)