Hubert Lau

All Publications

• Deep learning identifies histopathologic changes in bladder cancers associated with smoke exposure status. PloS one Eminaga, O., Lau, H., Shkolyar, E., Wardelmann, E., Abbas, M. 2024; 19 (7): e0305135

  Abstract

  Smoke exposure is associated with bladder cancer (BC). However, little is known about whether the histologic changes of BC can predict the status of smoke exposure. Given this knowledge gap, the current study investigated the potential association between histology images and smoke exposure status. A total of 483 whole-slide histology images of 285 unique cases of BC were available from multiple centers for BC diagnosis. A deep learning model was developed to predict the smoke exposure status and externally validated on BC cases. The development set consisted of 66 cases from two centers. The external validation consisted of 94 cases from remaining centers for patients who either never smoked cigarettes or were active smokers at the time of diagnosis. The threshold for binary categorization was fixed to the median confidence score (65) of the development set. On external validation, AUC was used to assess the randomness of predicted smoke status; we utilized latent feature presentation to determine common histologic patterns for smoke exposure status and mixed effect logistic regression models determined the parameter independence from BC grade, gender, time to diagnosis, and age at diagnosis. We used 2,000-times bootstrap resampling to estimate the 95% Confidence Interval (CI) on the external validation set. The results showed an AUC of 0.67 (95% CI: 0.58-0.76), indicating non-randomness of model classification, with a specificity of 51.2% and sensitivity of 82.2%. Multivariate analyses revealed that our model provided an independent predictor for smoke exposure status derived from histology images, with an odds ratio of 1.710 (95% CI: 1.148-2.54). Common histologic patterns of BC were found in active or never smokers. In conclusion, deep learning reveals histopathologic features of BC that are predictive of smoke exposure and, therefore, may provide valuable information regarding smoke exposure status.

  View details for DOI 10.1371/journal.pone.0305135

  View details for PubMedID 39083547

  View details for PubMedCentralID PMC11290674

• Artificial Intelligence Reveals Distinct Prognostic Subgroups of Muscle-Invasive Bladder Cancer on Histology Images. Cancers Eminaga, O., Leyh-Bannurah, S. R., Shariat, S. F., Krabbe, L. M., Lau, H., Xing, L., Abbas, M. 2023; 15 (20)

  Abstract

  Muscle-invasive bladder cancer (MIBC) is a highly heterogeneous and costly disease with significant morbidity and mortality. Understanding tumor histopathology leads to tailored therapies and improved outcomes. In this study, we employed a weakly supervised learning and neural architecture search to develop a data-driven scoring system. This system aimed to capture prognostic histopathological patterns observed in H&E-stained whole-slide images. We constructed and externally validated our scoring system using multi-institutional datasets with 653 whole-slide images. Additionally, we explored the association between our scoring system, seven histopathological features, and 126 molecular signatures. Through our analysis, we identified two distinct risk groups with varying prognoses, reflecting inherent differences in histopathological and molecular subtypes. The adjusted hazard ratio for overall mortality was 1.46 (95% CI 1.05-2.02; z: 2.23; p = 0.03), thus identifying two prognostic subgroups in high-grade MIBC. Furthermore, we observed an association between our novel digital biomarker and the squamous phenotype, subtypes of miRNA, mRNA, long non-coding RNA, DNA hypomethylation, and several gene mutations, including FGFR3 in MIBC. Our findings underscore the risk of confounding bias when reducing the complex biological and clinical behavior of tumors to a single mutation. Histopathological changes can only be fully captured through comprehensive multi-omics profiles. The introduction of our scoring system has the potential to enhance daily clinical decision making for MIBC. It facilitates shared decision making by offering comprehensive and precise risk stratification, treatment planning, and cost-effective preselection for expensive molecular characterization.

  View details for DOI 10.3390/cancers15204998

  View details for PubMedID 37894365

  View details for PubMedCentralID PMC10605516

• Efficient Augmented Intelligence Framework for Bladder Lesion Detection. JCO clinical cancer informatics Eminaga, O., Lee, T. J., Laurie, M., Ge, T. J., La, V., Long, J., Semjonow, A., Bogemann, M., Lau, H., Shkolyar, E., Xing, L., Liao, J. C. 2023; 7: e2300031

  Abstract

  Development of intelligence systems for bladder lesion detection is cost intensive. An efficient strategy to develop such intelligence solutions is needed.We used four deep learning models (ConvNeXt, PlexusNet, MobileNet, and SwinTransformer) covering a variety of model complexity and efficacy. We trained these models on a previously published educational cystoscopy atlas (n = 312 images) to estimate the ratio between normal and cancer scores and externally validated on cystoscopy videos from 68 cases, with region of interest (ROI) pathologically confirmed to be benign and cancerous bladder lesions (ie, ROI). The performance measurement included specificity and sensitivity at frame level, frame sequence (block) level, and ROI level for each case.Specificity was comparable between four models at frame (range, 30.0%-44.8%) and block levels (56%-67%). Although sensitivity at the frame level (range, 81.4%-88.1%) differed between the models, sensitivity at the block level (100%) and ROI level (100%) was comparable between these models. MobileNet and PlexusNet were computationally more efficient for real-time ROI detection than ConvNeXt and SwinTransformer.Educational cystoscopy atlas and efficient models facilitate the development of real-time intelligence system for bladder lesion detection.

  View details for DOI 10.1200/CCI.23.00031

  View details for PubMedID 37774313

• A magnetic hydrogel for the efficient retrieval of kidney stone fragments during ureteroscopy. Nature communications Ge, T. J., Roquero, D. M., Holton, G. H., Mach, K. E., Prado, K., Lau, H., Jensen, K., Chang, T. C., Conti, S., Sheth, K., Wang, S. X., Liao, J. C. 2023; 14 (1): 3711

  Abstract

  Only 60-75% of conventional kidney stone surgeries achieve complete stone-free status. Up to 30% of patients with residual fragments <2 mm in size experience subsequent stone-related complications. Here we demonstrate a stone retrieval technology in which fragments are rendered magnetizable with a magnetic hydrogel so that they can be easily retrieved with a simple magnetic tool. The magnetic hydrogel facilitates robust in vitro capture of stone fragments of clinically relevant sizes and compositions. The hydrogel components exhibit no cytotoxicity in cell culture and only superficial effects on ex vivo human urothelium and in vivo mouse bladders. Furthermore, the hydrogel demonstrates antimicrobial activity against common uropathogens on par with that of common antibiotics. By enabling the efficient retrieval of kidney stone fragments, our method can lead to improved stone-free rates and patient outcomes.

  View details for DOI 10.1038/s41467-023-38936-1

  View details for PubMedID 37349287

  View details for PubMedCentralID 5853829

• Clinicopathologic Features of Human Monkeypox Lymphadenitis. Histopathology Qian, Z. J., Gong, R., Mann, D. S., Walding, K., Miller, T., Nicholas, V., Kappagoda, S., Pinsky, B. A., Silva, O., Lau, H. D. 2023

  View details for DOI 10.1111/his.14878

  View details for PubMedID 36734592

• Sequential modeling for cystoscopic image classification Laurie, M., Eminaga, O., Shkolyar, E., Jia, X., Lee, T., Long, J., Islam, M., Lau, H., Xing, L., Liao, J. C. 2023

  View details for DOI 10.1117/12.2649334

• Randomized controlled trial investigating use of submucosal injection of EverLift in rates of complete resection of non-pedunculated 4-9mm polyps. International journal of colorectal disease Wei, M. T., Louie, C. Y., Chen, Y., Pan, J. Y., Quan, S. Y., Wong, R., Brown, R., Clark, M., Jensen, K., Lau, H., Friedland, S. 2022

  Abstract

  INTRODUCTION: Currently, cold snare polypectomy (CSP) without submucosal injection is recommended for removing polyps<10mm. Use of viscous submucosal agents has not been previously evaluated in CSP. We investigate the potential role of EverLift (GI Supply, Pennsylvania) in CSP.METHODS: The study is a single-center prospective randomized non-inferiority clinical trial evaluating CSP of non-pedunculated 4-9mm polyps, with or without submucosal injection of EverLift. Patients 18-80years of age presenting for colonoscopy were recruited. Eligible polyps underwent block randomization to CSP with or without EverLift. Following CSP, two biopsies were performed at the CSP site margin. The primary non-inferiority outcome was complete resection rate, defined by absence of residual polyp in the margin biopsies (non-inferiority margin-10%).RESULTS: A total of 291 eligible polyps underwent CSP, with 142 removed using EverLift. There was similar polyp size and distribution of pathology between the two groups. Overall, there was a low rate of positive margins with (1.4%) or without submucosal injection (2.8%), with no significant difference in complete resection (difference 1.28%, 95% CI:-2.66 to 5.42%), demonstrating non-inferiority of EverLift injection. Use of EverLift significantly increased CSP time (109.8 vs 38.8s, p<0.0001) and frequency of use of hemostatic clips (13.4 vs 3.6%, p=0.002).CONCLUSION: Submucosal injection of EverLift was non-inferior to CSP of 4-9mm polyps without injection and increased time for resection as well as use of hemostatic clips to control acute bleeding. Our results suggest that polypectomy of 4-9mm polyps can be safely performed without submucosal injection of EverLift.

  View details for DOI 10.1007/s00384-022-04136-4

  View details for PubMedID 35507047

• Randomized controlled Trial Investigating cold snare aNd forceps polypectomY among small POLYPs in rates of complete resection: the TINYPOLYP Trial. The American journal of gastroenterology Wei, M. T., Louie, C. Y., Chen, Y., Pan, J. Y., Quan, S. Y., Wong, R., Brown, R., Clark, M., Jensen, K., Lau, H., Friedland, S. 2022

  Abstract

  BACKGROUND: Optimizing complete resection during colonoscopy is important as residual neoplastic tissue may play a role in interval cancers. The United States Multi-Society Task Force recommends diminutive (<5mm) and small (6-9mm) polyps be removed by cold snare polypectomy (CSP). However, evidence is less clear whether CSP retains significant advantage over cold forceps polypectomy (CFP) for polyps <3mm.METHODS: This study is a single-center prospective non-inferiority randomized clinical trial evaluating CFP and CSP for nonpedunculated polyps <3mm. Patients >18 years of age undergoing colonoscopy for any indication were recruited. During each colonoscopy, polyps underwent block randomization to removal with CFP or CSP. Following polypectomy, two biopsies were taken from the polypectomy margin. The primary non-inferiority outcome was complete resection rate, defined by absence of residual polyp in the margin biopsies.RESULTS: A total of 179 patients were included. Patients had similar distribution in age, sex, race/ethnicity, as well as indication of procedure. A total of 279 polyps <3mm were identified, with 138 in the CSP group and 141 in the CFP group. Mean polypectomy time was longer for CSP compared to CFP (42.3 vs 23.2 seconds, p<0.001), though a higher proportion of polyps removed by CFP were removed in more than one piece compared to CSP (15.6 vs 3.6%, p<0.001). There were positive margin biopsies in 2 cases per cohort, with complete resection rate of 98.3% in both groups. There was no significant difference in cohorts in complete resection rates (difference in complete resection rates was 0.057%, 95% CI: -4.30 to 4.53%), demonstrating non-inferiority of CFP compared to CSP.CONCLUSIONS: Use of CFP was non-inferior to CSP in the complete resection of nonpedunculated polyps <3mm. CSP required significantly more time to perform compared to CFP. CFP should be considered an acceptable alternative to CSP for removal of polyps <3mm.

  View details for DOI 10.14309/ajg.0000000000001799

  View details for PubMedID 35467557

• Immunohistochemical Characterization of 120 Testicular Sex Cord-Stromal Tumors With an Emphasis on the Diagnostic Utility of SOX9, FOXL2, and SF-1. The American journal of surgical pathology Lau, H. D., Kao, C., Williamson, S. R., Cheng, L., Ulbright, T. M., Idrees, M. T. 2021

  Abstract

  Sex cord-stromal tumors (SCSTs) account for the second most common category of testicular neoplasms and include several entities that may show overlapping morphologies and present diagnostic challenges. We analyzed a cohort of 120 testicular SCSTs and investigated the diagnostic utility of SRY-box transcription factor 9 (SOX9), forkhead box protein L2 (FOXL2), and steroidogenic factor 1 (SF-1) immunohistochemical stains. The results were compared with the more commonly used SCST markers, inhibin alpha, calretinin, and Wilms' tumor 1 (WT1). SF-1 was overall the most sensitive stain (91%), followed by inhibin alpha (70%), calretinin (52%), FOXL2 (50%), SOX9 (47%), and WT1 (37%), but sensitivities varied by tumor type. SOX9 and calretinin were more commonly positive in sex cord elements versus stromal elements (62% vs. 27% and 47% vs. 9%, respectively), whereas FOXL2 was more commonly positive in stromal elements versus sex cord elements (100% vs. 55%) when excluding Leydig cell tumors from the stromal category. Although no individual stain was diagnostically specific, some immunophenotypic patterns were noted that may help in the subclassification of SCSTs. We conclude that SOX9, FOXL2, and SF-1 are useful immunohistochemical stains for confirming sex cord-stromal differentiation in testicular tumors and provide increased sensitivity as well as additional diagnostic information, especially when combined with the more commonly used inhibin alpha, calretinin, and WT1 immunostains. Although morphology is paramount for subclassification of SCSTs, knowledge of certain immunohistochemical patterns may be helpful for diagnostically challenging cases.

  View details for DOI 10.1097/PAS.0000000000001704

  View details for PubMedID 34232606

• Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor. The American Journal of dermatopathology Brown, R. A., Cloutier, J. M., Bahrani, E. n., Liman, A. n., Tasso, D. n., Palmer, A. n., Manning, M. A., Galperin, I. n., Rieger, K. E., Novoa, R. A., Lau, H. n., Louie, C. Y. 2021

  Abstract

  Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.

  View details for DOI 10.1097/DAD.0000000000001931

  View details for PubMedID 33767072

• Metastatic squamous cell carcinoma transformed from prostatic adenocarcinoma following androgen deprivation therapy: A case report with clinicopathologic and molecular findings. Diagnostic cytopathology Lau, H. D., Clark, M. 2020; 48 (12): E14-E17

  Abstract

  Squamous cell carcinoma (SCC) of the prostate is a rare and clinically aggressive entity that may arise de novo or through transformation of prostatic adenocarcinoma, typically following hormonal or radiation therapy. Confirmation of prostatic origin, especially when evaluating a metastatic focus, often requires correlation with clinical and imaging findings, as the morphologic and immunohistochemical features of SCC are not organ-specific. Comprehensive genomic profiling (CGP) may provide additional information useful for confirming the primary site and for identifying potential targeted therapy options. CGP data may also contribute to our understanding of the molecular basis of squamous differentiation in prostatic malignancies. However, these data are limited, and to our knowledge, there are only three previously published cases of prostatic SCC with reported CGP findings. Herein, we report a case of metastatic keratinizing SCC diagnosed by core needle biopsy in a 68-year-old man with a history of prostatic adenocarcinoma status post radical prostatectomy and androgen deprivation therapy (ADT). NKX3.1 immunohistochemistry was negative. CGP was performed, and a TMPRSS2-ERG fusion, among other genetic alterations, was detected, supporting a diagnosis of metastatic SCC transformed from prostatic adenocarcinoma following ADT. This case supports the use of CGP or other molecular techniques not only to query potential targeted therapy options but also to refine the diagnosis and confirm the primary site of disease in cases with non-specific morphologic and immunophenotypic features, such as SCC.

  View details for DOI 10.1002/dc.24539

  View details for PubMedID 32628337

• Targeted deep sequencing of cell-free DNA in serous body cavity fluids with malignant, suspicious, and benign cytology. Cancer cytopathology Yang, S., Mooney, K. L., Libiran, P., Jones, C. D., Joshi, R., Lau, H. D., Stehr, H., Berry, G. J., Zehnder, J. L., Long, S. R., Kong, C. S., Kunder, C. A. 2019

  Abstract

  BACKGROUND: Liquid biopsy using cell-free DNA (cfDNA) presents new opportunities for solid tumor genotyping. While studies have demonstrated the utility of cfDNA from plasma, cfDNA from other body fluids remains underexplored.METHODS: We evaluated the molecular features and clinicopathologic correlates of cfDNA from serous body cavity fluids by performing hybrid capture-based next-generation sequencing (NGS) on cfDNA isolated from residual effusion supernatants. Twenty-one serous effusions from pleural (n=15), peritoneal (n=5), and pericardial (n=1) cavity were analyzed.RESULTS: The supernatants provided a median cfDNA concentration of 10.3ng/L. Notably, all effusions were sequenced successfully to a median depth >1000*, revealing a broad range of genetic alterations including single nucleotide variants, small insertions and deletions, amplifications, and fusions. Specifically, pathogenic alterations were identified in all malignant fluids (13/13), all fluids suspicious for malignancy (2/2), and 1 benign fluid (1/6) from a patient with metastatic cancer. To validate our findings, we examined matching results from 11 patients who underwent additional testing using formalin-fixed, paraffin-embedded (FFPE) specimens. In 8 patients, the paired results between FFPE and supernatant testing were concordant, whereas in the remaining 3 patients, supernatant analysis identified additional variants likely associated with resistance to targeted therapies. Additional comparison between FFPE and supernatant testing showed no difference in DNA concentration (P=.5), depth of coverage (P=.6), or allele frequency of pathogenic mutations (P=.7).CONCLUSION: cfDNA isolated from serous body cavity fluids represents a promising source of genomic input for targeted NGS.

  View details for DOI 10.1002/cncy.22205

  View details for PubMedID 31751001

• A Clinicopathologic and Molecular Analysis of Fumarate Hydratase-Deficient Renal Cell Carcinoma in 32 Patients. The American journal of surgical pathology Lau, H. D., Chan, E., Fan, A. C., Kunder, C. A., Williamson, S. R., Zhou, M., Idrees, M. T., Maclean, F. M., Gill, A. J., Kao, C. 2019

  Abstract

  Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and recently described entity associated with hereditary leiomyomatosis and RCC syndrome. FH-deficient RCC may show variable clinical and pathologic findings, but commonly presents with locally advanced and metastatic disease and carries a poor prognosis. We identified 32 patients with FH-deficient RCC, confirmed by FH immunohistochemistry (IHC) and/or FH mutation analysis, and performed a retrospective review of the clinical and pathologic features. Median age at presentation was 43 years (range, 18 to 69y), and the M:F ratio was 2.2:1. Median tumor size was 6.5cm (range, 2.5 to 28cm), and 71% presented at stage ≥pT3a. After a median follow-up of 16 months (range, 1 to 118mo) in 26 patients, 19% showed no evidence of disease, 31% were alive with disease, and 50% were dead of disease. The vast majority of cases showed multiple histologic growth patterns, with papillary (52%) being the most common predominant pattern, followed by solid (21%), cribriform/sieve-like (14%), sarcomatoid (3%), tubular (3%), cystic (3%), and low-grade oncocytic (3%). Viral inclusion-like macronucleoli with perinucleolar clearing were present in almost all cases (96%). All cases were evaluated using FH IHC, and 3 cases (9%) showed retained FH expression. Nineteen cases had germline or tumor mutation analysis confirming a FH mutation, with 79% (11/14) of cases showing mutations within coding regions and 21% (3/14) showing mutations within intronic splice-sites. By IHC, 97% (32/33) of cases were negative for CK7, 93% (27/29) were negative for p63, and 52% (15/29) were negative for GATA3. All cases stained were positive for PAX8 and showed retained succinate dehydrogenase B expression. Our overall findings show that FH-deficient RCC is considerably heterogenous in morphology and frequently behaves aggressively. Suspicion for this entity should be raised even in the absence of predominantly papillary architecture and characteristic nucleolar features. We have included cases with uncommonly seen features, including 4 cases with predominantly cribriform/sieve-like architecture as well as one case with pure low-grade oncocytic morphology (9y of clinical follow-up without evidence of disease). Although FH IHC is a useful tool for identifying cases of FH-deficient RCC, not all cases of FH-deficient RCC show loss of FH staining, and FH mutation analysis should be considered for patients with suspicious clinical or pathologic features, even in cases with retained FH IHC expression.

  View details for DOI 10.1097/PAS.0000000000001372

  View details for PubMedID 31524643

• Evaluation of Diagnostic Accuracy and a Practical Algorithmic Approach for the Diagnosis of Renal Masses by FNA CANCER CYTOPATHOLOGY Lau, H. D., Kong, C. S., Kao, C. 2018; 126 (9): 782–96

  View details for DOI 10.1002/cncy.22037

  View details for Web of Science ID 000454533300006

• Flow Immunophenotyping of Benign Lymph Nodes Sampled by FNA: Representative With Diagnostic Pitfalls CANCER CYTOPATHOLOGY Scott, G. D., Lau, H. D., Kurzer, J. H., Kong, C. S., Gratzinger, D. A. 2018; 126 (9): 797–808

  View details for DOI 10.1002/cncy.22038

  View details for Web of Science ID 000454533300007

• An integrated flow cytometry analysis of 286 mature B cell neoplasms identifies CD13 as a useful marker for diagnostic subtyping. International journal of laboratory hematology Lau, H., Nagy, A., Atwater, S. K., Cascio, M. J., Ohgami, R. S. 2018

  Abstract

  INTRODUCTION: CD13 is a myeloid associated antigen, which may be expressed by a subset of B cell lymphomas; however, the significance of its expression along with other B cell associated antigens is not well characterized.METHODS: Two hundred and eighty-six mature B cell neoplasms with flow cytometric analysis performed at the time of diagnosis were identified. Expression of CD13, CD45, CD19, CD20, CD5, CD10, CD38, CD22, CD23, FMC7, and kappa and lambda light chains was assessed for each case and correlated with clinicopathologic features.RESULTS: CD13 expression was associated specifically with cases of lymphoplasmacytic lymphoma (LPL) (16/26)- and FMC7-positive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (11/30). No cases of follicular lymphoma (FL) expressed CD13 (0/48). Across all B cell neoplasms, CD13 expression positively correlated with FMC7 co-expression and kappa light chain restriction and negatively correlated with CD10 co-expression and lambda light chain restriction. No significant association of CD13 with overall or disease free survival in B cell neoplasms was seen.CONCLUSION: CD13 expression is present more often in LPL- and FMC7-positive CLL/SLL than other mature B cell lymphoma subtypes and absent in cases of FL and may be a useful feature for diagnostic subtyping.

  View details for PubMedID 30066366

• Cardiovascular pathology in 2 young adults with sudden, unexpected death due to coronary aneurysms from Kawasaki disease in childhood CARDIOVASCULAR PATHOLOGY Shimizu, C., Sood, A., Lau, H. D., Oharaseki, T., Takahashi, K., Krous, H. F., Campman, S., Burns, J. C. 2015; 24 (5): 310-316

  Abstract

  Coronary artery aneurysms (CAA) may remain silent after Kawasaki disease (KD) until adulthood when myocardial ischemia can lead to sudden death. We postulated that there would be young adults with sudden, unexpected death due to CAA from KD who would have a state-mandated autopsy performed by the San Diego County Medical Examiner's Office (SDCMEO).We reviewed all autopsy cases <35years of age from 1997 to 2012 at the SDCMEO with a cardiovascular cause of death (n=154).We found 2 cases meeting inclusion criteria. Case 1 was a 22-year-old Korean male with chronic ischemic changes due to a partially occluded and diffusely calcified 15mm aneurysm at the bifurcation of the left main coronary artery. Interview of the mother revealed that this patient had been diagnosed with KD complicated by giant aneurysms at age two years. Case 2 was a 30-year-old Hispanic male with myocardial infarction due to thrombosis of a calcified left anterior descending artery aneurysm. Histologic findings included diffuse myocardial fibrosis and a recanalized aneurysm in the right coronary artery. Interview of the family revealed a KD-compatible illness in childhood. Immunohistochemical staining showed expression of transforming growth factor β pathway molecules in the aneurysmal arterial wall.In a medical examiner's office serving a population of approximately 3 million people, 2 of 154 (1.3%) cardiovascular deaths in persons <35years were attributed to cardiovascular complications of KD in childhood. Antecedent KD should be considered in the evaluation of all cases of sudden, unexpected death in young adults.

  View details for DOI 10.1016/j.carpath.2015.02.006

  View details for Web of Science ID 000361183400007

  View details for PubMedID 25791439

  View details for PubMedCentralID PMC4547904

• Synthesis of Dihydropyrimidinones/Thiopyrimidinones: Nafion-Ga, an Efficient "Green" Lewis Acid Catalyst for the Biginelli Reaction CATALYSIS LETTERS Prakash, G. K., Lau, H., Panja, C., Bychinskaya, I., Ganesh, S. K., Zaro, B., Mathew, T., Olah, G. A. 2014; 144 (12): 2012-2020

  View details for DOI 10.1007/s10562-014-1364-8

  View details for Web of Science ID 000345843700004

• Differential Expression of miR-145 in Children with Kawasaki Disease PLOS ONE Shimizu, C., Kim, J., Stepanowsky, P., Trinh, C., Lau, H. D., Akers, J. C., Chen, C., Kanegaye, J. T., Tremoulet, A., Ohno-Machado, L., Burns, J. C. 2013; 8 (3)

  Abstract

  Kawasaki disease is an acute, self-limited vasculitis of childhood that can result in structural damage to the coronary arteries. Previous studies have implicated the TGF-β pathway in disease pathogenesis and generation of myofibroblasts in the arterial wall. microRNAs are small non-coding RNAs that modulate gene expression at the post-transcriptional level and can be transported between cells in extracellular vesicles. To understand the role that microRNAs play in modifying gene expression in Kawasaki disease, we studied microRNAs from whole blood during the acute and convalescent stages of the illness.RNA isolated from the matched whole blood of 12 patients with acute and convalescent Kawasaki disease were analyzed by sequencing of small RNA. This analysis revealed six microRNAs (miRs-143, -199b-5p, -618, -223, -145 and -145* (complementary strand)) whose levels were significantly elevated during the acute phase of Kawasaki disease. The result was validated using targeted qRT-PCR using an independent cohort (n = 16). miR-145, which plays a critical role in the differentiation of neutrophils and vascular smooth muscle cells, was expressed at high levels in blood samples from acute Kawasaki disease but not adenovirus-infected control patients (p = 0.005). miR-145 was also detected in small extracellular vesicles isolated from acute Kawasaki disease plasma samples. Pathway analysis of the predicted targets of the 6 differentially expressed microRNAs identified the TGF-β pathway as the top pathway regulated by microRNAs in Kawasaki disease.Sequencing of small RNA species allowed discovery of microRNAs that may participate in Kawasaki disease pathogenesis. miR-145 may participate, along with other differentially expressed microRNAs, in regulating expression of genes in the TGF-β pathway during the acute illness. If the predicted target genes are confirmed, our findings suggest a model of Kawasaki disease pathogenesis whereby miR-145 modulates TGF-β signaling in the arterial wall.

  View details for DOI 10.1371/journal.pone.0058159

  View details for Web of Science ID 000316936100081

  View details for PubMedID 23483985

  View details for PubMedCentralID PMC3590129

• Precise Control of Protein Concentration in Living Cells ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Lau, H. D., Yaegashi, J., Zaro, B. W., Pratt, M. R. 2010; 49 (45): 8458-8461

  View details for DOI 10.1002/anie.201003073

  View details for Web of Science ID 000284015600031

  View details for PubMedID 20878685