Chao Ma

All Publications

• Engineered mucus-tethering bispecific nanobodies enhance mucosal immunity against respiratory pathogens. Nature nanotechnology Zhao, L., O'Donnell, K. L., Dubey, M., Wang, Y., Martinez, N. R., Zhang, Y., Steininger, H. M., Ma, C., Mallajosyula, V., Lee, L. L., Lachmansingh, R. N., Stavitsky, S., Takematsu, E., Hoover, M. Y., Chen, H., Guo, J., Wu, A., Ma, Y., Wang, X., Nalin, A. P., Jeong, S. D., Lu, W. J., Nguyen, P. K., Clancy, C. S., Tal, M. C., Xiao, J., Longaker, M. T., Lee, A. S., Kim, B. Y., Ambrosi, T. H., Weissman, I. L., Davis, M. M., Hasenkrug, K. J., Chien, Y. H., Jiang, W., Marzi, A., Chan, C. K. 2026

  Abstract

  Despite advances in vaccine and antiviral drug development, the prevention of respiratory viral infection and transmission remains a substantial challenge worldwide. One obvious limitation of these approaches is that they do not provide robust protection at the initial site of infection, which is the respiratory mucosa. Currently, strategies to enhance mucosal immunity against respiratory pathogens remain lacking. Here we engineered mucus-tethering bispecific nanobodies designed to provide the simultaneous neutralization of viruses by binding to their surface proteins and the entrapment of viruses within the mucus by securing them to mucin. Compared with conventional non-mucus-tethering nanobodies, these mucus-tethering bispecific nanobodies demonstrated increased retention in the respiratory tract, provided enhanced protection against influenza viral infection in mice and reduced SARS-CoV-2 transmission in hamsters. Together, our findings represent a promising strategy for enhancing mucosal defences against respiratory viruses by blocking viral entry and limiting onward transmission.

  View details for DOI 10.1038/s41565-025-02107-8

  View details for PubMedID 41565781

  View details for PubMedCentralID 8023351

• Cajanin transcriptionally disrupts the Siglec15/NFATc1 signaling cascade to attenuate osteoclast fusion and bone resorption. International immunopharmacology Ma, C., Mo, L., Wang, Z., He, W., Niu, W., Goodman, S. B., Goodnough, L. H., Liu, Y. 2025; 168 (Pt 2): 115726

  Abstract

  Osteoclast fusion is a critical step for bone resorption, and its dysregulation contributes to pathological bone loss such as postmenopausal osteoporosis. Siglec15, a membrane-bound lectin, has emerged as a key regulator of osteoclast precursor recognition and fusion. Herein, it is reported that Cajanin, a natural small-molecule compound, potently inhibits osteoclastogenesis and bone resorption both in vitro and in vivo. Cajanin treatment suppressed actin ring formation, bone resorptive activity and the expression of osteoclastic markers including Ctsk and Mmp9 in a dose-dependent manner. Transcriptomic profiling revealed that Cajanin downregulated key fusion mediators such as Siglec15, DC-STAMP, OC-STAMP and NFATc1. Gene enrichment analysis identified attenuated MAPK and NF-κB signaling, which was validated by decreased phosphorylation of ERK, JNK and p38, increased IκB-α levels and reduced nuclear translocation of p65. Moreover, Cajanin significantly suppressed NFATc1 expression and nuclear localization. In an ovariectomy-induced bone loss model, Cajanin preserved trabecular bone architecture and reduced TRAP-positive osteoclasts. Collectively, these findings demonstrate that Cajanin transcriptionally disrupts the Siglec15-NFATc1 signaling axis, thereby impairing osteoclast fusion and bone resorption, and highlight its potential as a therapeutic candidate for selectively targeting pathological osteoclast fusion in osteolytic diseases.

  View details for DOI 10.1016/j.intimp.2025.115726

  View details for PubMedID 41260165

• Combination of Distinct Vascular Stem/Progenitor Cells for Neovascularization and Ischemic Rescue. Arteriosclerosis, thrombosis, and vascular biology Zhao, L., Lee, A. S., Sasagawa, K., Sokol, J., Wang, Y., Ransom, R. C., Zhao, X., Ma, C., Steininger, H. M., Koepke, L. S., Borrelli, M. R., Brewer, R. E., Lee, L. L., Huang, X., Ambrosi, T. H., Sinha, R., Hoover, M. Y., Seita, J., Weissman, I. L., Wu, J. C., Wan, D. C., Xiao, J., Longaker, M. T., Nguyen, P. K., Chan, C. K. 2023

  Abstract

  Peripheral vascular disease remains a leading cause of vascular morbidity and mortality worldwide despite advances in medical and surgical therapy. Besides traditional approaches, which can only restore blood flow to native arteries, an alternative approach is to enhance the growth of new vessels, thereby facilitating the physiological response to ischemia.The ActinCreER/R26VT2/GK3 Rainbow reporter mouse was used for unbiased in vivo survey of injury-responsive vasculogenic clonal formation. Prospective isolation and transplantation were used to determine vessel-forming capacity of different populations. Single-cell RNA-sequencing was used to characterize distinct vessel-forming populations and their interactions.Two populations of distinct vascular stem/progenitor cells (VSPCs) were identified from adipose-derived mesenchymal stromal cells: VSPC1 is CD45-Ter119-Tie2+PDGFRa-CD31+CD105highSca1low, which gives rise to stunted vessels (incomplete tubular structures) in a transplant setting, and VSPC2 which is CD45-Ter119-Tie2+PDGFRa+CD31-CD105lowSca1high and forms stunted vessels and fat. Interestingly, cotransplantation of VSPC1 and VSPC2 is required to form functional vessels that improve perfusion in the mouse hindlimb ischemia model. Similarly, VSPC1 and VSPC2 populations isolated from human adipose tissue could rescue the ischemic condition in mice.These findings suggest that autologous cotransplantation of synergistic VSPCs from nonessential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.

  View details for DOI 10.1161/ATVBAHA.122.317943

  View details for PubMedID 37051932

• Integrated Bioinformatic Analysis of the Shared Molecular Mechanisms Between Osteoporosis and Atherosclerosis. Frontiers in endocrinology Mo, L., Ma, C., Wang, Z., Li, J., He, W., Niu, W., Chen, Z., Zhou, C., Liu, Y. 2022; 13: 950030

  Abstract

  Osteoporosis and atherosclerosis are common in the elderly population, conferring a heavy worldwide burden. Evidence links osteoporosis and atherosclerosis but the exact underlying common mechanism of its occurrence is unclear. The purpose of this study is to further explore the molecular mechanism between osteoporosis and atherosclerosis through integrated bioinformatic analysis.The microarray data of osteoporosis and atherosclerosis in the Gene Expression Omnibus (GEO) database were downloaded. The Weighted Gene Co-Expression Network Analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to identify the co-expression genes related to osteoporosis and atherosclerosis. In addition, the common gene targets of osteoporosis and atherosclerosis were analyzed and screened through three public databases (CTD, DISEASES, and GeneCards). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape. Then, the common microRNAs (miRNAs) in osteoporosis and atherosclerosis were screened out from the Human microRNA Disease Database (HMDD) and the target genes of whom were predicted through the miRTarbase. Finally, the common miRNAs-genes network was constructed by Cytoscape software.The results of common genes analysis showed that immune and inflammatory response may be a common feature in the pathophysiology of osteoporosis and atherosclerosis. Six hub genes (namely, COL1A1, IBSP, CTSD, RAC2, MAF, and THBS1) were obtained via taking interaction of different analysis results. The miRNAs-genes network showed that has-let-7g might play an important role in the common mechanisms between osteoporosis and atherosclerosis.This study provides new sights into shared molecular mechanisms between osteoporosis and atherosclerosis. These common pathways and hub genes may offer promising clues for further experimental studies.

  View details for DOI 10.3389/fendo.2022.950030

  View details for PubMedID 35937806

  View details for PubMedCentralID PMC9353191