Stephen Liangtjan Trisno

All Publications

• Conjugation of Peptide Ligands to AAV Towards Pancreatic Cell AAV Gene Delivery Trisno, S., Kay, M. CELL PRESS. 2025

  View details for Web of Science ID 001573749200046

• Esophageal pathology and the aerodigestive triple endoscopy for pediatric recurrent croup. International journal of pediatric otorhinolaryngology Trisno, S. L., Carver, M., Sidell, D., Khan, S. 2025; 193: 112367

  Abstract

  Recurrent croup (RC) is characterized by recurrent episodes of stridor, barking cough, and hoarseness. While viral infections are the primary cause in croup, RC is thought to be caused by non-infectious etiologies such as structural airway abnormalities, allergic disorders, airway hyperresponsiveness and gastroesophageal reflux (GERD). Recent studies have suggested a potential link between esophageal diseases, particularly GERD/reflux esophagitis and eosinophilic esophagitis (EoE), and RC. This retrospective study aims to explore the association between esophageal disorders and RC through a multidisciplinary approach. A total of 68 patients with RC were identified in our aerodigestive center, 47 of whom underwent dual or triple endoscopy. Of these, 17 patients (36 %) were found to have esophageal disease, including EoE (15 %) and reflux esophagitis (19 %). Notably, food allergies were significantly more prevalent in the EoE group, and all patients with EoE had reported GI symptoms previously. While airway abnormalities were common across all groups, there were no significant differences between patients with and without esophageal disease. The study highlights the prevalence of esophageal diseases in patients with RC, particularly EoE, and a multidisciplinary aerodigestive evaluation may be beneficial for diagnosing concomitant esophageal conditions. Further studies are needed to determine the causal relationship between esophageal disorders and RC.

  View details for DOI 10.1016/j.ijporl.2025.112367

  View details for PubMedID 40318473

• Generation of DNA Aptamers Against Pancreatic Surface Receptors Towards AAV Cell-Specific Targeting Trisno, S. L., Puzzo, F., Kay, M. A. CELL PRESS. 2023: 228

  View details for Web of Science ID 001045144201068

• Case Report: Esophageal Bronchus in a Neonate, With Image, Histological, and Molecular Analysis. Frontiers in pediatrics Trisno, S. L., Higano, N. S., Kechele, D., Nasr, T., Chung, W., Zorn, A. M., Woods, J. C., Wells, J. M., Kingma, P. S. 2021; 9: 707822

  Abstract

  In this case report, we describe the clinical course of a neonate who presented initially with respiratory distress and later with choking during feeding. He was subsequently found to have an esophageal bronchus to the right upper lung lobe, a rare communicating bronchopulmonary foregut malformation. Histological and molecular analysis of the fistula and distal tissues revealed that the proximal epithelium from the esophageal bronchus has characteristics of both esophageal and respiratory epithelia. Using whole exome sequencing of the patient's and parent's DNA, we identified gene variants that are predicted to impact protein function and thus could potentially contribute to the phenotype. These will be the subject of future functional analysis.

  View details for DOI 10.3389/fped.2021.707822

  View details for PubMedID 34307264

  View details for PubMedCentralID PMC8298819

• Disruption of a hedgehog-foxf1-rspo2 signaling axis leads to tracheomalacia and a loss of sox9+ tracheal chondrocytes. Disease models & mechanisms Nasr, T., Holderbaum, A. M., Chaturvedi, P., Agarwal, K., Kinney, J. L., Daniels, K., Trisno, S. L., Ustiyan, V., Shannon, J. M., Wells, J. M., Sinner, D., Kalinichenko, V. V., Zorn, A. M. 2020; 14 (2)

  Abstract

  Congenital tracheomalacia, resulting from incomplete tracheal cartilage development, is a relatively common birth defect that severely impairs breathing in neonates. Mutations in the Hedgehog (HH) pathway and downstream Gli transcription factors are associated with tracheomalacia in patients and mouse models; however, the underlying molecular mechanisms are unclear. Using multiple HH/Gli mouse mutants including one that mimics Pallister-Hall Syndrome, we show that excessive Gli repressor activity prevents specification of tracheal chondrocytes. Lineage tracing experiments show that Sox9+ chondrocytes arise from HH-responsive splanchnic mesoderm in the fetal foregut that expresses the transcription factor Foxf1. Disrupted HH/Gli signaling results in 1) loss of Foxf1 which in turn is required to support Sox9+ chondrocyte progenitors and 2) a dramatic reduction in Rspo2, a secreted ligand that potentiates Wnt signaling known to be required for chondrogenesis. These results reveal a HH-Foxf1-Rspo2 signaling axis that governs tracheal cartilage development and informs the etiology of tracheomalacia.

  View details for DOI 10.1242/dmm.046573

  View details for PubMedID 33328171

  View details for PubMedCentralID PMC7875488

• Esophageal Organoids from Human Pluripotent Stem Cells Delineate Sox2 Functions during Esophageal Specification. Cell stem cell Trisno, S. L., Philo, K. E., McCracken, K. W., Catá, E. M., Ruiz-Torres, S., Rankin, S. A., Han, L., Nasr, T., Chaturvedi, P., Rothenberg, M. E., Mandegar, M. A., Wells, S. I., Zorn, A. M., Wells, J. M. 2018; 23 (4): 501-515.e7

  Abstract

  Tracheal and esophageal disorders are prevalent in humans and difficult to accurately model in mice. We therefore established a three-dimensional organoid model of esophageal development through directed differentiation of human pluripotent stem cells. Sequential manipulation of bone morphogenic protein (BMP), Wnt, and RA signaling pathways was required to pattern definitive endoderm into foregut, anterior foregut (AFG), and dorsal AFG spheroids. Dorsal AFG spheroids grown in a 3D matrix formed human esophageal organoids (HEOs), and HEO cells could be transitioned into two-dimensional cultures and grown as esophageal organotypic rafts. In both configurations, esophageal tissues had proliferative basal progenitors and a differentiated stratified squamous epithelium. Using HEO cultures to model human esophageal birth defects, we identified that Sox2 promotes esophageal specification in part through repressing Wnt signaling in dorsal AFG and promoting survival. Consistently, Sox2 ablation in mice causes esophageal agenesis. Thus, HEOs present a powerful platform for modeling human pathologies and tissue engineering.

  View details for DOI 10.1016/j.stem.2018.08.008

  View details for PubMedID 30244869

  View details for PubMedCentralID PMC6225525

• Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nature medicine Workman, M. J., Mahe, M. M., Trisno, S., Poling, H. M., Watson, C. L., Sundaram, N., Chang, C. F., Schiesser, J., Aubert, P., Stanley, E. G., Elefanty, A. G., Miyaoka, Y., Mandegar, M. A., Conklin, B. R., Neunlist, M., Brugmann, S. A., Helmrath, M. A., Wells, J. M. 2017; 23 (1): 49-59

  Abstract

  The enteric nervous system (ENS) of the gastrointestinal tract controls many diverse functions, including motility and epithelial permeability. Perturbations in ENS development or function are common, yet there is no human model for studying ENS-intestinal biology and disease. We used a tissue-engineering approach with embryonic and induced pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining human-PSC-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity, as measured by rhythmic waves of calcium transients. ENS-containing HIOs grown in vivo formed neuroglial structures similar to a myenteric and submucosal plexus, had functional interstitial cells of Cajal and had an electromechanical coupling that regulated waves of propagating contraction. Finally, we used this system to investigate the cellular and molecular basis for Hirschsprung's disease caused by a mutation in the gene PHOX2B. This is, to the best of our knowledge, the first demonstration of human-PSC-derived intestinal tissue with a functional ENS and how this system can be used to study motility disorders of the human gastrointestinal tract.

  View details for DOI 10.1038/nm.4233

  View details for PubMedID 27869805

  View details for PubMedCentralID PMC5562951

• On the activation of integrin αIIbβ3: outside-in and inside-out pathways. Biophysical journal Mehrbod, M., Trisno, S., Mofrad, M. R. 2013; 105 (6): 1304-15

  Abstract

  Integrin αIIbβ3 is a member of the integrin family of transmembrane proteins present on the plasma membrane of platelets. Integrin αIIbβ3 is widely known to regulate the process of thrombosis via activation at its cytoplasmic side by talin and interaction with the soluble fibrinogen. It is also reported that three groups of interactions restrain integrin family members in the inactive state, including a set of salt bridges on the cytoplasmic side of the transmembrane domain of the integrin α- and β-subunits known as the inner membrane clasp, hydrophobic packing of a few transmembrane residues on the extracellular side between the α- and β-subunits that is known as the outer membrane clasp, and the key interaction group of the βA domain (located on the β-subunit head domain) with the βTD (proximal to the plasma membrane on the β-subunit). However, molecular details of this key interaction group as well as events that lead to detachment of the βTD and βA domains have remained ambiguous. In this study, we use molecular dynamics models to take a comprehensive outside-in and inside-out approach at exploring how integrin αIIbβ3 is activated. First, we show that talin's interaction with the membrane-proximal and membrane-distal regions of integrin cytoplasmic-transmembrane domains significantly loosens the inner membrane clasp. Talin also interacts with an additional salt bridge (R734-E1006), which facilitates integrin activation through the separation of the integrin's α- and β-subunits. The second part of our study classifies three types of interactions between RGD peptides and the extracellular domains of integrin αIIbβ3. Finally, we show that the interaction of the Arg of the RGD sequence may activate integrin via disrupting the key interaction group between K350 on the βA domain and S673/S674 on the βTD.

  View details for DOI 10.1016/j.bpj.2013.07.055

  View details for PubMedID 24047981

  View details for PubMedCentralID PMC3785890

• Removal of spurious coherence in MEG source-space coherence analysis. IEEE transactions on bio-medical engineering Sekihara, K., Owen, J. P., Trisno, S., Nagarajan, S. S. 2011; 58 (11): 3121-9

  Abstract

  Source-space coherence analysis has become a popular method to estimate functional connectivity based on MEG/EEG. Source-space analysis involves solving the inverse problem, estimating the time courses of specific brain regions, and then examining the coherence between activities at different brain regions. However, source-space coherence analysis can be confounded by spurious coherence caused due to the leakage properties of the inverse algorithm employed. Such spurious coherence is typically manifested as an artifactual large peak around the seed voxel, called seed blur, in the resulting coherence images. This seed blur often obscures important details of brain interactions. This paper proposes the use of the imaginary part of the coherence to remove the spurious coherence caused by the leakage of an imaging algorithm. We present a theoretical analysis that explains how the use of imaginary part can remove this spurious coherence. We then present results from both computer simulations and experiments using resting-state MEG data which demonstrate the validity of our analysis.

  View details for DOI 10.1109/TBME.2011.2162514

  View details for PubMedID 21824842

  View details for PubMedCentralID PMC4096348