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Biomedical subjects

Eric C Huang

Publications and source records attributed to Eric C Huang.

4 recordsLinked to original sources

An integrated single-cell and spatial transcriptomic atlas of thyroid cancer progression identifies prognostic fibroblast subpopulations.

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts (myCAFs) that are intimately associated with invasive tumor cells and correlate with poor prognosis, lymph node metastasis, and disease progression in thyroid carcinoma. We also revealed a population of inflammatory CAFs that are distant to tumor cells and are found in the inflammatory stromal microenvironment of autoimmune thyroiditis. Together, our study provides spatial profiling of thyroid cancer evolution in samples with mixed WDTC/ATC histopathology and identifies a prognostic myCAF subtype with potential clinical utility in predicting aggressive disease in both children and adults.

Humans↗

Accommodative microfluctuations and iris contour.

Mechanical interaction between aqueous humor, iris, and intraocular structures can alter the iris profile from its normal curvature. In particular, significant changes to the iris profile occur during accommodation as the anterior lens movement forces the iris into greater posterior bowing. We extended a previous mathematical model of the anterior segment and investigated the response of this coupled fluid-solid system due to accommodative microfluctuations. The results showed that the system response exhibited the same waveform as the stimulus for small-amplitude microfluctuations generally associated with the high-frequency component. Low-frequency microfluctuations with relatively larger amplitudes elicited a response different from the stimulus, indicating that the forces generated by the lens movement significantly affected the aqueous-iris mechanical interaction.

Accommodation, Ocular↗

Cross-reactivity of T lymphocytes recognizing a human cytotoxic T-lymphocyte epitope within BK and JC virus VP1 polypeptides.

A transgenic mouse model was used to identify an HLA-A*02-restricted epitope within the VP1 polypeptide of a human polyomavirus, BK virus (BKV), which is associated with polyomavirus-associated nephropathy in kidney transplant patients. Peptide stimulation of splenocytes from mice immunized with recombinant modified vaccinia virus Ankara expressing BKV VP1 resulted in expansion of cytotoxic T lymphocytes (CTLs) recognizing the sequence LLMWEAVTV corresponding to amino acid residues 108 to 116 (BKV VP1p108). These effector T-cell populations represented functional CTLs as assessed by cytotoxicity and cytokine production and were cross-reactive against antigen-presenting cells pulsed with a peptide corresponding to the previously described JC virus (JCV) VP1 homolog sequence ILMWEAVTL (JCV VP1p100) (I. J. Koralnik et al., J. Immunol. 168:499-504, 2002). A panel of 10 healthy HLA-A*02 human volunteers and two kidney transplant recipients were screened for T-cell immunity to this BK virus VP1 epitope by in vitro stimulation of their peripheral blood mononuclear cells (PBMC) with the BKV VP1p108 peptide, followed by tetramer labeling combined with simultaneous assays to detect intracellular cytokine production and degranulation. PBMC from 4/10 subjects harbored CTL populations that recognized both the BKV VP1p108 and the JCV VP1p100 peptides with comparable efficiencies as measured by tetramer binding, gamma interferon production, and degranulation. CTL responses to the JCV VP1p100 epitope have been associated with prolonged survival in progressive multifocal leukoencephalopathy patients (R. A. Du Pasquier et al., Brain 127:1970-1978, 2004; I. J. Koralnik et al., J. Immunol. 168:499-504, 2002). Given that both human polyomaviruses are resident in a high proportion of healthy individuals and that coinfection occurs (W. A. Knowles et al., J. Med. Virol. 71:115-123, 2003), our findings suggest a reinterpretation of this protective T-cell immunity, suggesting that the same VP1 epitope is recognized in HLA-A*02 persons in response to either BK or JC virus infection.

Animals↗

Active iris mechanics and pupillary block: steady-state analysis and comparison with anatomical risk factors.

Primary angle-closure glaucoma arises when the iris physically obstructs outflow of aqueous humor, increasing the intraocular pressure and damaging the optic nerve. Pupillary block, the predominant mechanism for angle closure, is believed to be driven by mechanical interaction between the aqueous humor and the iris. We performed steady-state simulations of this coupled fluid-solid system, including an active sphincter to control pupil constriction. Model results compared favorably against Mapstone's pupil-blocking force analysis. We also evaluated anatomical risk factors and quantified their contributions to pupillary block and angle closure. The results showed that greater lens curvature and shorter iris-zonule distance contribute significantly to pupillary block and the associated narrowing of the angle. Surprisingly, the model predicted that maximum pupillary block and angle closure occur at the minimum pupil dilation, contradicting the clinical observation that angle closure is most severe in dark conditions. This discrepancy suggests the involvement of one or more phenomena not captured by our current model.

Animals↗