Songnan Wang

All Publications

• 2-5A is an immunotransmitter that fuels RNase L immunity. Immunity Wang, S., Li, L. 2025; 58 (4): 770-772

  Abstract

  cGAS-cGAMP-STING and OAS-2-5A-RNase L are evolutionarily convergent innate immune pathways. cGAMP acts as an immunotransmitter; what about 2-5A? In this issue of Immunity, Huai etal. map the transfer of 2-5A between cells, establishing it as a bona fide immunotransmitter.

  View details for DOI 10.1016/j.immuni.2025.03.007

  View details for PubMedID 40203803

• Pilot Implementation of a Simulation-Based Surgical Curriculum for Rwandan Medical Interns. Journal of surgical education Kirsch, M., Mpirimbanyi, C., Wang, S., Kansayisa, G., Gasakure, M., Ntirenganya, F., Lin, Y. 2025; 82 (5): 103475

  Abstract

  Develop and implement a standardized surgical training curriculum for Rwandan medical interns to better prepare them for general practice at district hospitals. Assess the curriculum's impact on participants surgical knowledge and technical skills and identify areas for iterative improvement.A 2-day surgical curriculum combining theory-based didactics and hands-on, simulation-based skills training was developed and implemented. Rwandan medical interns were surveyed before and after participation to evaluate their comfort with various core surgical topics and skills.The study was conducted in Kigali, Rwanda.35 participated, Rwandan medical interns who had completed or were completing their surgical rotations were enrolled in the study.Significant improvements were observed in participants' confidence in both surgical knowledge and techniques after completing the curriculum. Participants identified simulation as a valuable training technique but reported barriers such as limited access to simulation resources. Most participants reported that the curriculum was beneficial, realistic, and something they would recommend to others.Rwanda faces a shortage of surgical specialists necessitating an expanded scope of practice for general practitioners, including performing common surgical procedures. Our pilot surgical skills curriculum for Rwandan interns demonstrates potential in addressing this need. Future iterations will refine the curriculum and expand its implementation to all Rwandan medical interns to enhance the surgical care that they will provide as general practitioners.

  View details for DOI 10.1016/j.jsurg.2025.103475

  View details for PubMedID 40073675

• Cost-effectiveness analysis of valvular surgery in high- and low- to middle-income countries: A scoping review. World journal of surgery Mlambo, V., Hyles, K., Wang, S., Lin, Y. 2024

  Abstract

  Global disparities in valvular surgery services exist. Cost-effectiveness analysis (CEA) and cost-utility analysis can be used to guide national investment decisions. This scoping review aims to synthesize economic evaluations for valvular surgery by income settings and provide recommendations.A systematic literature review identified primary CEAs or CUAs in English comparing surgical management strategies for valvular heart disease. MEDLINE, Embase, CINAHL, Web of Science, and Business Source Complete were searched using keywords "valvular surgery," "valve disease," "cost-effectiveness," and "cost-benefit analysis". Articles comparing outcomes or costs only were excluded. Search results were uploaded and screened on COVIDENCE. Variables from eligible articles were charted in a spreadsheet.Twenty articles were eligible, six from low- and middle-income countries (LMICs) and 14 from high-income countries (HICs). In HICs, the top conditions were degenerative aortic valve disease (7/14) and mitral valve disease (4/14) compared to congenital (2/6) and rheumatic heart diseases (2/6) in LMICs. HICs evaluated new technologies and techniques, whereas LMICs compared different valve types or surgery versus no intervention. Most articles used published studies (12/20) or databases (7/20) to conduct their CEA and quality-adjusted life years was the most common effectiveness measure (12/20). Comparator interventions were cost-effective in all LMIC articles and in 8/14 for HICs.Economic evaluations are mostly conducted in HICs and for adult conditions. More analyses in LMICs are needed. This can be facilitated by maintaining databases, documenting costs, and implementing quality of life assessments.

  View details for DOI 10.1002/wjs.12381

  View details for PubMedID 39428550

• Identification of the extracellular membrane protein ENPP3 as a major cGAMP hydrolase and innate immune checkpoint. Cell reports Mardjuki, R., Wang, S., Carozza, J., Zirak, B., Subramanyam, V., Abhiraman, G., Lyu, X., Goodarzi, H., Li, L. 2024: 114209

  Abstract

  2'3'-Cyclic guanosine monophosphate (GMP)-AMP (cGAMP) is a second messenger synthesized upon detection of cytosolic double-stranded DNA (dsDNA) and passed between cells to facilitate downstream immune signaling. Ectonucleotide pyrophosphatase phosphodiesterase I (ENPP1), an extracellular enzyme, was the only metazoan hydrolase known to regulate cGAMP levels to dampen anti-cancer immunity. Here, we uncover ENPP3 as the second and likely the only other metazoan cGAMP hydrolase under homeostatic conditions. ENPP3 has a tissue expression pattern distinct from ENPP1's and accounts for all cGAMP hydrolysis activity in ENPP1-deficient mice. Importantly, we also show that, as with ENPP1, selectively abolishing ENPP3's cGAMP hydrolysis activity results in diminished cancer growth and metastasis of certain tumor types in a stimulator of interferon genes (STING)-dependent manner. Both ENPP1 and ENPP3 are extracellular enzymes, suggesting the dominant role that extracellular cGAMP must play as a mediator of cell-cell innate immune communication. Our work demonstrates that ENPP1 and ENPP3 non-redundantly dampen extracellular cGAMP-STING signaling, pointing to ENPP3 as a target for cancer immunotherapy.

  View details for DOI 10.1016/j.celrep.2024.114209

  View details for PubMedID 38749434

• ENPP1 is an innate immune checkpoint of the anticancer cGAMP-STING pathway in breast cancer. Proceedings of the National Academy of Sciences of the United States of America Wang, S., Böhnert, V., Joseph, A. J., Sudaryo, V., Skariah, G., Swinderman, J. T., Yu, F. B., Subramanyam, V., Wolf, D. M., Lyu, X., Gilbert, L. A., Van't Veer, L. J., Goodarzi, H., Li, L. 2023; 120 (52): e2313693120

  Abstract

  Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) expression correlates with poor prognosis in many cancers, and we previously discovered that ENPP1 is the dominant hydrolase of extracellular cGAMP: a cancer-cell-produced immunotransmitter that activates the anticancer stimulator of interferon genes (STING) pathway. However, ENPP1 has other catalytic activities and the molecular and cellular mechanisms contributing to its tumorigenic effects remain unclear. Here, using single-cell RNA-seq, we show that ENPP1 in both cancer and normal tissues drives primary breast tumor growth and metastasis by dampening extracellular 2'3'-cyclic-GMP-AMP (cGAMP)-STING-mediated antitumoral immunity. ENPP1 loss-of-function in both cancer cells and normal tissues slowed primary tumor growth and abolished metastasis. Selectively abolishing the cGAMP hydrolysis activity of ENPP1 phenocopied ENPP1 knockout in a STING-dependent manner, demonstrating that restoration of paracrine cGAMP-STING signaling is the dominant anti-cancer mechanism of ENPP1 inhibition. Finally, ENPP1 expression in breast tumors deterministically predicated whether patients would remain free of distant metastasis after pembrolizumab (anti-PD-1) treatment followed by surgery. Altogether, ENPP1 blockade represents a strategy to exploit cancer-produced extracellular cGAMP for controlled local activation of STING and is therefore a promising therapeutic approach against breast cancer.

  View details for DOI 10.1073/pnas.2313693120

  View details for PubMedID 38117852

• Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells. Cell reports Takahashi, K., Jeong, D., Wang, S., Narita, M., Jin, X., Iwasaki, M., Perli, S. D., Conklin, B. R., Yamanaka, S. 2020; 31 (9): 107715

  Abstract

  Previous studies have suggested that the loss of the translation initiation factor eIF4G1 homolog NAT1 induces excessive self-renewability of naive pluripotent stem cells (PSCs); yet the role of NAT1 in the self-renewal and differentiation of primed PSCs is still unclear. Here, we generate a conditional knockout of NAT1 in primed PSCs and use the cells for the functional analyses of NAT1. Our results show that NAT1 is required for the self-renewal and neural differentiation of primed PSCs. In contrast, NAT1 deficiency in naive pluripotency attenuates the differentiation to all cell types. We also find that NAT1 is involved in efficient protein expression of an RNA uridyltransferase, TUT7. TUT7 is involved in the neural differentiation of primed PSCs via the regulation of human endogenous retrovirus accumulation. These data demonstrate the essential roles of NAT1 and TUT7 in the precise transition of stem cell fate.

  View details for DOI 10.1016/j.celrep.2020.107715

  View details for PubMedID 32492424

  View details for PubMedCentralID PMC8195978

• Hypoxia and matrix viscoelasticity sequentially regulate endothelial progenitor cluster-based vasculogenesis. Science advances Blatchley, M. R., Hall, F., Wang, S., Pruitt, H. C., Gerecht, S. 2019; 5 (3): eaau7518

  Abstract

  Vascular morphogenesis is the formation of endothelial lumenized networks. Cluster-based vasculogenesis of endothelial progenitor cells (EPCs) has been observed in animal models, but the underlying mechanism is unknown. Here, using O2-controllabe hydrogels, we unveil the mechanism by which hypoxia, co-jointly with matrix viscoelasticity, induces EPC vasculogenesis. When EPCs are subjected to a 3D hypoxic gradient ranging from <2 to 5%, they rapidly produce reactive oxygen species that up-regulate proteases, most notably MMP-1, which degrade the surrounding extracellular matrix. EPC clusters form and expand as the matrix degrades. Cell-cell interactions, including those mediated by VE-cadherin, integrin-β2, and ICAM-1, stabilize the clusters. Subsequently, EPC sprouting into the stiffer, intact matrix leads to vascular network formation. In vivo examination further corroborated hypoxia-driven clustering of EPCs. Overall, this is the first description of how hypoxia mediates cluster-based vasculogenesis, advancing our understanding toward regulating vascular development as well as postnatal vasculogenesis in regeneration and tumorigenesis.

  View details for DOI 10.1126/sciadv.aau7518

  View details for PubMedID 30906859

  View details for PubMedCentralID PMC6426463

• Modulator Effects on the Water-Based Synthesis of Zr/Hf Metal-Organic Frameworks: Quantitative Relationship Studies between Modulator, Synthetic Condition, and Performance CRYSTAL GROWTH & DESIGN Hu, Z., Castano, I., Wang, S., Wang, Y., Peng, Y., Qan, Y., Chi, C., Wang, X., Zhao, D. 2016; 16 (4): 2295-2301

  View details for DOI 10.1021/acs.cgd.6b00076

  View details for Web of Science ID 000373747700062

• Transcriptional Landscape of Cardiomyocyte Maturation. Cell reports Uosaki, H., Cahan, P., Lee, D. I., Wang, S., Miyamoto, M., Fernandez, L., Kass, D. A., Kwon, C. 2015; 13 (8): 1705-16

  Abstract

  Decades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM) differentiation. However, control of the CM maturation that is subsequently required to generate adult myocytes remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and identified a large number of genes whose expression shifts gradually and continuously during maturation. We generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs), which show discrete sets of key transcriptional regulators and pathways activated or suppressed during CM maturation. We developed a GRN-based program named MatStat(CM) that indexes CM maturation status. MatStat(CM) reveals that pluripotent-stem-cell-derived CMs mature early in culture but are arrested at the late embryonic stage with aberrant regulation of key transcription factors. Our study provides a foundation for understanding CM maturation.

  View details for DOI 10.1016/j.celrep.2015.10.032

  View details for PubMedID 26586429

  View details for PubMedCentralID PMC4662925

• Combination of Optimization and Metalated-Ligand Exchange: An Effective Approach to Functionalize UiO-66(Zr) MOFs for CO2 Separation. Chemistry (Weinheim an der Bergstrasse, Germany) Hu, Z., Faucher, S., Zhuo, Y., Sun, Y., Wang, S., Zhao, D. 2015; 21 (48): 17246-55

  Abstract

  The strategy to functionalize water-stable metal-organic frameworks (MOFs) in order to improve their CO2 uptake capacities for efficient CO2 separation remains limited and challenging. We herein present an effective approach to functionalize a prominent water-stable MOF, UiO-66(Zr), by a combination of optimization and metalated-ligand exchange. In particular, by systematic optimization, we have successfully obtained UiO-66(Zr) of the highest BET surface area reported so far (1730 m(2)  g(-1) ). Moreover, it shows a hybrid Type I/IV N2 isotherm at 77 K and a mesopore size of 3.9 nm for the first time. The UiO-66 MOF underwent a metalated-ligand-exchange (MLE) process to yield a series of new UiO-66-type MOFs, among which UiO-66-(COONa)2 -EX and UiO-66-(COOLi)4 -EX MOFs have both enhanced CO2 working capacity and IAST CO2 /N2 selectivity. Our approach has thus suggested an alternative design to achieve water-stable MOFs with high crystallinity and gas uptake for efficient CO2 separation.

  View details for DOI 10.1002/chem.201503078

  View details for PubMedID 26477589