Medical Microbiology Commons^™

Oleuropein Suppresses Endometriosis Progression And Improves The Fertility Of Mice With Endometriosis, Yuri Park, Yeon Jean Cho, Nuri Sung, Mi Jin Park, Xiaoming Guan, William E Gibbons, Bert W O'Malley, Sang Jun Han

Faculty, Staff and Students Publications

BACKGROUND: Endometriosis is an estrogen-dependent inflammatory reproductive disease. Therefore, systematic estrogen depletion and anti-inflammatory drugs are the current treatment for endometriosis. However, current endometriosis treatments have low efficacy and cause adverse effects in endometriosis patients. Consequently, alternative endometriosis treatments targeting endometriosis-specific factors are in demand. In this context, ERβ was selected as a druggable target for endometriosis due to its critical role in progression. Therefore, selective targeting of ERβ without inhibiting ERα activity would be a new paradigm for endometriosis treatment to overcome the low efficacy and adverse effects of hormonal endometriosis therapy.

METHODS: Cell-based ERβ and ERα activity assay …

Lipid Surfaces And Glutamate Anions Enhance Formation Of Dynamic Biomolecular Condensates Containing Bacterial Cell Division Protein Ftsz And Its Dna-Bound Regulator Slma, Gianfranco Paccione, Miguel Á Robles-Ramos, Carlos Alfonso, Marta Sobrinos-Sanguino, William Margolin, Silvia Zorrilla, Begoña Monterroso, Germán Rivas

Faculty, Staff and Student Publications

Dynamic biomolecular condensates formed by liquid-liquid phase separation can regulate the spatial and temporal organization of proteins, thus modulating their functional activity in cells. Previous studies showed that the cell division protein FtsZ from Escherichia coli formed dynamic phase-separated condensates with nucleoprotein complexes containing the FtsZ spatial regulator SlmA under crowding conditions, with potential implications for condensate-mediated spatiotemporal control of FtsZ activity in cell division. In the present study, we assessed formation of these condensates in the presence of lipid surfaces and glutamate ions to better approximate the E. coli intracellular environment. We found that potassium glutamate substantially promoted the …

Modified Messengers: Flatworm Stem Cells And Regeneration Are Guarded By Rna Methylation, Blair W Benham-Pyle

Faculty, Staff and Students Publications

The contribution of RNA modifications to whole-body regeneration remains unclear. In this issue, Dagan et al (2022) show that m6a mRNA pathway components are critically required for stem cell differentiation, survival, and tissue renewal in the planarian Schmidtea mediterranea.

The Breast Cancer Microenvironment And Lipoprotein Lipase: Another Negative Notch For A Beneficial Enzyme?, Zhu-Hong Chen, Yu-Ling Cui, Jing-Ting Sun, Yu-Ting Li, Chi Zhang, Yang-Ming Zhang, Ze-Yang Li, Yu-Xuan Shang, Min-Hua Ni, Bo Hu, Lin-Feng Yan, Wen Wang

Faculty, Staff and Student Publications

Objectives: To quantitatively summarize the specific changes in brain structure and function in migraine patients.

Methods: A literature screening of migraine was conducted from inception to Sept 1, 2022, in PubMed, Web of Science, Cochrane Library, and Medline databases using the keyword combination of "migraine and MRI." Activation likelihood estimation (ALE) was performed to assess the differentiation of functional connectivity (FC), regional homogeneity (ReHo), and gray matter volume (GMV) of migraine patients.

Results: Eleven voxel-based morphometry (VBM) studies and 25 resting-state fMRI (rs-fMRI) studies (16 FC and 9 ReHo studies) were included in this study. ALE analysis revealed the ReHo …

Triphenyl Phosphate Activates Estrogen Receptor Α/Nf-Κb/ Cyclin D1 Signaling To Stimulate Cell Cycle Progression In Human Ishikawa Endometrial Cancer Cells, Hyun Young Kwon, Seung Bin Park, Myoungseok Han, Jung-Woo Park, Yongmin Lee, Sang Jun Han, Youngmin Kwon, Yeon Jean Cho

Faculty, Staff and Students Publications

OBJECTIVE: Triphenyl phosphate (TPHP) is one of the most commonly used organophosphorus flame retardants that may accumulate in the environment. However, its effects on human reproductive organs have not been well studied. We aimed to investigate the in vitro effects of TPHP in human Ishikawa endometrial cancer cells to elucidate how TPHP exposure disrupts intracellular signaling and cell proliferation in reproductive tissues.

METHODS: Human Ishikawa endometrial cancer cells were exposed to TPHP.

RESULTS: Exposure to TPHP elevated the levels of estrogen receptor (ER) α and progesterone receptor-B and reduced ER β in human Ishikawa endometrial cancer cells. TPHP stimulated phosphoinositide …

Steroid Receptor Coactivator-3 Inhibition Generates Breast Cancer Antitumor Immune Microenvironment, Sang Jun Han, Nuri Sung, Jin Wang, Bert W O'Malley, David M Lonard

Faculty, Staff and Students Publications

BACKGROUND: The tumor immune microenvironment (TIME) generated by cancer-infiltrating immune cells has a crucial role in promoting or suppressing breast cancer progression. However, whether the steroid receptor coactivator-3 (SRC-3) modulates TIME to progress breast cancer is unclear. Therefore, the present study evaluates whether SRC-3 generates a tumor-promoting TIME in breast tumors using a syngeneic immune-intact mouse model of breast cancer.

METHODS: We employed E0771 and 4T1 breast cancer in immune-intact syngeneic female C57BL/6 and BALB/c mice, respectively. SI-2, a specific small-molecule inhibitor of SRC-3, was administered daily (2.5 mg/kg) to E0771 and 4T1 breast tumor-bearing immune-intact mice. In addition, SRC-3 …

Interferon Signaling In The Endometrium And In Endometriosis, Yuri Park, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is an estrogen-dependent inflammatory disease that develops in reproductive-aged women who experience pelvic pain and infertility. Even though endometriosis is not a new disease, its molecular etiology has not been clearly elucidated. Defects in the immune system might be one of the factors that promote endometriosis progression. For example, elevated levels of proinflammatory cytokines are associated with endometriosis. Interferon is one of the cytokines that is elevated in endometriotic tissues compared with normal endometrium. Therefore, high interferon levels play a crucial role in endometriosis progression. In addition to endometriosis, however, interferon has a critical role in endometrial function, particularly …

Sensitive Image-Based Chromatin Binding Assays Using Inducible Erα To Rapidly Characterize Estrogenic Chemicals And Mixtures, Adam T Szafran, Maureen G Mancini, Fabio Stossi, Michael A Mancini

Faculty, Staff and Students Publications

The United States Environmental Protection Agency (EPA) has been pursuing new high throughput in vitro assays to characterize endocrine disrupting chemicals (EDCs) that interact with estrogen receptor signaling. We characterize two new PRL-HeLa cell models expressing either inducible C-terminal (iGFP-ER) or N-terminal (iER-GFP) tagged estrogen receptor-α (ERα) that allows direct visualization of chromatin binding. These models are an order of magnitude more sensitive, detecting 87 - 93% of very weak estrogens tested compared to only 27% by a previous PRL-HeLa variant and compares favorably to the 73% detected by an EPA-developed computational model using in vitro data. Importantly, the chromatin …

Elevated Nras Expression During Dcis Is A Potential Driver For Progression To Basal-Like Properties And Local Invasiveness, Ze-Yi Zheng, Hanan Elsarraj, Jonathan T Lei, Yan Hong, Meenakshi Anurag, Long Feng, Hilda Kennedy, Yichao Shen, Flora Lo, Zifan Zhao, Bing Zhang, Xiang H-F Zhang, Ossama W Tawfik, Fariba Behbod, Eric C Chang

Faculty, Staff and Students Publications

BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression. In this study, we investigated whether NRAS expression at the DCIS stage can control transition from luminal DCIS to basal-like invasive breast cancers.

METHODS: Wilcoxon rank-sum test was performed to assess expression of NRAS in DCIS compared to invasive breast tumors in patients. NRAS …

Structural And Functional Diversity Of Type Iv Secretion Systems, Melissa R Cruz, Shane Cristy, Shantanu Guha, Giuseppe Buda De Cesare, Elena Evdokimova, Hiram Sanchez, Dominika Borek, Pedro Miramón, Junko Yano, Paul L Fidel, Alexei Savchenko, David R Andes, Peter J Stogios, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also …

The Temporal Impulse Response Function In Infantile Nystagmus, Gal Avital, Felicia Kuperwaser, Andrew W Pountain, Keenan A Lacey, Erin E Zwack, Magdalena Podkowik, Bo Shopsin, Victor J Torres, Itai Yanai

Faculty, Staff and Student Publications

Innate immune recognition of bacterial pathogens is a key determinant of the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact the course of infection. To gain insight into host response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one of which consists of four sub-states, reflecting inflammatory activation. Infection with six additional bacterial species—Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella enterica—recapitulates these states, though at …

Oxidation Of Two Cysteines Within Yeast Hsp70 Impairs Proteostasis While Directly Triggering An Hsf1-Dependent Cytoprotective Response, Alec Santiago, Kevin A Morano

Faculty, Staff and Student Publications

Neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases affect millions of Americans every year. One factor linked to the formation of aggregates associated with these diseases is damage sustained to proteins by oxidative stress. Management of protein misfolding by the ubiquitous Hsp70 chaperone family can be modulated by modification of two key cysteines in the ATPase domain by oxidizing or thiol-modifying compounds. To investigate the biological consequences of cysteine modification on the Hsp70 Ssa1 in budding yeast, we generated cysteine null (cysteine to serine) and oxidomimetic (cysteine to aspartic acid) mutant variants of both C264 and C303 and demonstrate …

Wellness In The Face Of Frailty Among Older Adults In First Nations Communities, Morgan Slater, Gabrielle Bruser, Roseanne Sutherland, Melissa K Andrew, Wayne Warry, Kristen M Jacklin, Jennifer D Walker

Faculty, Staff and Student Publications

OBJECTIVES: First Nations people report high levels of wellness despite high rates of chronic illness. Our goal was to understand the factors associated with wellness among First Nations adults in Ontario who were considered frail.

METHODS: Using the First Nations Regional Health Survey, we created a profile of First Nations adults (aged 45+) who were categorized as "frail" (weighted sample size = 8121). We used multivariate logistic regression to determine associations between wellness (as measured by self-reported physical, emotional, mental, and spiritual balance) and determinants of health.

RESULTS: Rates of reported wellness were high among those who were frail, ranging …

Identification Of An Early Survival Prognostic Gene Signature For Localized Osteosarcoma Patients, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Faculty, Staff and Students Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …

Plasma Protein Biomarkers For Primary Graft Dysfunction After Lung Transplantation: A Single-Center Cohort Analysis, Lourdes Chacon-Alberty, Rupa S Kanchi, Shengbin Ye, Camila Hochman-Mendez, Daoud Daoud, Cristian Coarfa, Meng Li, Sandra L Grimm, Maher Baz, Ivan Rosas, Gabriel Loor

Faculty, Staff and Students Publications

The clinical use of circulating biomarkers for primary graft dysfunction (PGD) after lung transplantation has been limited. In a prospective single-center cohort, we examined the use of plasma protein biomarkers as indicators of PGD severity and duration after lung transplantation. The study comprised 40 consecutive lung transplant patients who consented to blood sample collection immediately pretransplant and at 6, 24, 48, and 72 h after lung transplant. An expert grader determined the severity and duration of PGD and scored PGD at T0 (6 h after reperfusion), T24, T48, and T72 h post-reperfusion using the 2016 ISHLT consensus guidelines. A bead-based …

Overlapping And Distinct Functions Of The Paralogous Pagr Regulators Of Bacillus Anthracis, Ileana D Corsi, Theresa M Koehler

Faculty, Staff and Student Publications

The Bacillus anthracis pagA gene, encoding the protective antigen component of anthrax toxin, is part of a bicistronic operon on pXO1 that codes for its own repressor, PagR1. In addition to the pagAR1 operon, PagR1 regulates sap and eag, two chromosome genes encoding components of the surface layer, a mounting structure for surface proteins involved in virulence. Genomic studies have revealed a PagR1 paralog, PagR2, encoded by a gene on pXO2. The amino acid sequences of the paralogues are 71% identical and show similarity to the ArsR family of transcription regulators. We determined that the expression of either rPagR1 …

Comparative Analysis Of Co-Cultured Amniotic Cell-Conditioned Media With Cell-Free Amniotic Fluid Reveals Differential Effects On Epithelial-Mesenchymal Transition And Myofibroblast Activation, Naiyou Liu, Charles M Bowen, Mohammadali M Shoja, Karen Larissa Castro De Pereira, Laxmi Priya Dongur, Antonio Saad, William K Russell, Thomas Christopher Broderick, Jeffrey H Fair, William Samuel Fagg

Faculty, Staff and Student Publications

Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we …

Mab21l4 Deficiency Drives Squamous Cell Carcinoma Via Activation Of Ret, Ankit Srivastava, Cristina Tommasi, Dane Sessions, Angela Mah, Tomas Bencomo, Jasmine M Garcia, Tiffany Jiang, Michael Lee, Joseph Y Shen, Lek Wei Seow, Audrey Nguyen, Kimal Rajapakshe, Cristian Coarfa, Kenneth Y Tsai, Vanessa Lopez-Pajares, Carolyn S Lee

Faculty, Staff and Students Publications

UNLABELLED: Epithelial squamous cell carcinomas (SCC) most commonly originate in the skin, where they display disruptions in the normally tightly regulated homeostatic balance between keratinocyte proliferation and terminal differentiation. We performed a transcriptome-wide screen for genes of unknown function that possess inverse expression patterns in differentiating keratinocytes compared with cutaneous SCC (cSCC), leading to the identification of MAB21L4 (C2ORF54) as an enforcer of terminal differentiation that suppresses carcinogenesis. Loss of MAB21L4 in human cSCC organoids increased expression of RET to enable malignant progression. In addition to transcriptional upregulation of RET, deletion of MAB21L4 preempted recruitment of the CacyBP-Siah1 E3 ligase …

Ppm1d In Solid And Hematologic Malignancies: Friend And Foe?, Linda Zhang, Joanne I Hsu, Margaret A Goodell

Faculty, Staff and Students Publications

In the face of constant genomic insults, the DNA damage response (DDR) is initiated to preserve genome integrity; its disruption is a classic hallmark of cancer. Protein phosphatase Mg2+/Mn2+-dependent 1D (PPM1D) is a central negative regulator of the DDR that is mutated or amplified in many solid cancers. PPM1D overexpression is associated with increased proliferative and metastatic behavior in multiple solid tumor types and patients with PPM1D-mutated malignancies have poorer prognoses. Recent findings have sparked an interest in the role of PPM1D in hematologic malignancies. Acquired somatic mutations may provide hematopoietic stem cells with a competitive advantage, leading to a …

Distinguishing Intrathyroid Parathyroid Adenoma From Colloid Nodules And Papillary Thyroid Carcinomas Using Multiphasic Multidetector Computed Tomography, J Matthew Debnam, T Linda Chi, Michael Kwon, Jia Sun, Dawid Schellingerhout, Brandon T Golant, Salmaan Ahmed, Nancy D Perrier, Thinh Vu

Faculty, Staff and Student Publications

OBJECTIVE: The aim of the study is to determine whether multiphase multidetector computed tomography (4D-MDCT) can differentiate between intrathyroid parathyroid adenomas (ITPAs), colloid nodules, and papillary thyroid carcinoma (PTC).

METHODS: We studied 22 ITPAs, 22 colloid nodules, and 11 PTCs in 55 patients. Hounsfield unit (HU) values of the nodules were measured on 4D-MDCT in the precontrast, arterial, venous, and delayed phases. Raw HU values, phase with peak enhancement, and washout percentages between the phases were evaluated.

RESULTS: Regardless of size, all ITPAs (22/22) showed peak enhancement in the arterial phase, which was significantly greater than both colloid nodules (15/22) …

Amphotericin B Resistance In Leishmania Mexicana: Alterations To Sterol Metabolism And Oxidative Stress Response, Edubiel A Alpizar-Sosa, Nur Raihana Binti Ithnin, Wenbin Wei, Andrew W Pountain, Stefan K Weidt, Anne M Donachie, Ryan Ritchie, Emily A Dickie, Richard J S Burchmore, Paul W Denny, Michael P Barrett

Faculty, Staff and Student Publications

Amphotericin B is increasingly used in treatment of leishmaniasis. Here, fourteen independent lines of Leishmania mexicana and one L. infantum line were selected for resistance to either amphotericin B or the related polyene antimicrobial, nystatin. Sterol profiling revealed that, in each resistant line, the predominant wild-type sterol, ergosta-5,7,24-trienol, was replaced by other sterol intermediates. Broadly, two different profiles emerged among the resistant lines. Whole genome sequencing then showed that these distinct profiles were due either to mutations in the sterol methyl transferase (C24SMT) gene locus or the sterol C5 desaturase (C5DS) gene. In three lines an additional deletion of …

Associations Between Maternal Reports Of Periconceptional Fever From Miscellaneous Causes And Structural Birth Defects, Nithya Lakshmi Mohan Dass, Lorenzo D Botto, Sarah C Tinker, Mark A Canfield, Richard H Finnell, Michael Shayne Gallaway, Syed Shahrukh Hashmi, Adrienne T Hoyt, Wendy N Nembhard, Dorothy K Waller, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

BACKGROUND: Associations between birth defects and fevers attributed to colds, influenza, and urinary tract infections (UTIs) have been observed in previous studies. Our aim was to study associations between birth defects and fevers attributed to other causes.

METHODS: We analyzed data from 34,862 participants in the National Birth Defects Prevention Study, a multistate case-control study of major structural birth defects. Using multivariable logistic regression, we assessed the association between maternal report of fever during early pregnancy due to causes other than colds, influenza, or UTI and 36 categories of birth defects.

RESULTS: Maternal reports of fever due to other causes …

Gene Expression Signatures Identify Biologically And Clinically Distinct Tuberculosis Endotypes, Andrew R Dinardo, Tanmay Gandhi, Jan Heyckendorf, Sandra L Grimm, Kimal Rajapakshe, Tomoki Nishiguchi, Maja Reimann, H Lester Kirchner, Jaqueline Kahari, Qiniso Dlamini, Christoph Lange, Torsten Goldmann, Sebastian Marwitz, Dzif-Tb Cohort Study Group, Abhimanyu, Jeffrey D Cirillo, Stefan H E Kaufmann, Mihai G Netea, Reinout Van Crevel, Anna M Mandalakas, Cristian Coarfa

Faculty, Staff and Students Publications

BACKGROUND:In vitro, animal model and clinical evidence suggests that tuberculosis is not a monomorphic disease, and that host response to tuberculosis is protean with multiple distinct molecular pathways and pathologies (endotypes). We applied unbiased clustering to identify separate tuberculosis endotypes with classifiable gene expression patterns and clinical outcomes.

METHODS: A cohort comprised of microarray gene expression data from microbiologically confirmed tuberculosis patients was used to identify putative endotypes. One microarray cohort with longitudinal clinical outcomes was reserved for validation, as were two RNA-sequencing (seq) cohorts. Finally, a separate cohort of tuberculosis patients with functional immune responses was evaluated …

Gray And White Matter Abnormality In Patients With T2dm-Related Cognitive Dysfunction: A Systemic Review And Meta-Analysis, Teng Ma, Ze-Yang Li, Ying Yu, Bo Hu, Yu Han, Min-Hua Ni, Yu-Xiang Huang, Hao-Han Chen, Wen Wang, Lin-Feng Yan, Guang-Bin Cui

Faculty, Staff and Student Publications

Aims/hypothesis

Brain structure abnormality in patients with type 2 diabetes mellitus (T2DM)-related cognitive dysfunction (T2DM-CD) has been reported for decades in magnetic resonance imaging (MRI) studies. However, the reliable results were still unclear. This study aimed to make a systemic review and meta-analysis to find the significant and consistent gray matter (GM) and white matter (WM) alterations in patients with T2DM-CD by comparing with the healthy controls (HCs).

Methods

Published studies were systemically searched from PubMed, MEDLINE, Cochrane Library and Web of Science databases updated to November 14, 2021. Studies reporting abnormal GM or WM between patients with T2DM-CD and …

Changes Of Brain Function In Patients With Type 2 Diabetes Mellitus Measured By Different Analysis Methods: A New Coordinate-Based Meta-Analysis Of Neuroimaging, Ze-Yang Li, Teng Ma, Ying Yu, Bo Hu, Yu Han, Hao Xie, Min-Hua Ni, Zhu-Hong Chen, Yang-Ming Zhang, Yu-Xiang Huang, Wen-Hua Li, Wen Wang, Lin-Feng Yan, Guang-Bin Cui

Faculty, Staff and Student Publications

OBJECTIVE: Neuroimaging meta-analysis identified abnormal neural activity alterations in patients with type 2 diabetes mellitus (T2DM), but there was no consistency or heterogeneity analysis between different brain imaging processing strategies. The aim of this meta-analysis was to determine consistent changes of regional brain functions in T2DM

METHODS: Since the indicators obtained using varied post-processing methods reflect different neurophysiological and pathological characteristics, we further conducted a coordinate-based meta-analysis (CBMA) of the two categories of neuroimaging literature, which were grouped according to similar data processing methods: one group included regional homogeneity (ReHo), independent component analysis (ICA), and degree centrality (DC) studies, while …

Exome Sequencing Identifies Genetic Variants In Anophthalmia And Microphthalmia, Jingjing Li, Wei Yang, Yuejun Jessie Wang, Chen Ma, Cynthia J Curry, Daniel Mcgoldrick, Deborah A Nickerson, Jessica X Chong, Elizabeth E Blue, James C Mullikin, Jennita Reefhuis, Wendy N Nembhard, Paul A Romitti, Martha M Werler, Marilyn L Browne, Andrew F Olshan, Richard H Finnell, Marcia L Feldkamp, Faith Pangilinan, Lynn M Almli, Mike J Bamshad, Lawrence C Brody, Mary M Jenkins, Gary M Shaw, University Of Washington Center For Mendelian Genomics, Nisc Comparative Sequencing Program, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 …

Patients With Lung Cancer Of Different Racial Backgrounds Harbor Distinct Immune Cell Profiles, Yitian Xu, Licheng Zhang, Jose Thaiparambil, Sunny Mai, Dimuthu Nuwan Perera, Jilu Zhang, Ping-Ying Pan, Cristian Coarfa, Kenneth Ramos, Shu-Hsia Chen, Randa El-Zein

Faculty, Staff and Students Publications

UNLABELLED: Tumors accumulated with infiltrated immune cells (hot tumors) have a higher response rate to immune checkpoint blockade, when compared with those with minimal T-cell infiltration (cold tumors). We report here that patients with lung cancer with different racial backgrounds harbored distinct immune cell profiles in the tumor microenvironment. Compared with African Americans (AA), Caucasian Americans (CA) exhibited increased immune cell infiltration and vasculature, and increased survival. Changes of survival and immune profile were most pronounced among active smokers and nonsmokers, compared with former smokers and total patients. Neighborhood analysis showed that immune cells accumulated around cancer cells in CAs …

Early Growth Response 1 Transcription Factor Is Essential For The Pathogenic Properties Of Human Endometriotic Epithelial Cells, Vineet K Maurya, Maria M Szwarc, Rodrigo Fernandez-Valdivia, David M Lonard, Song Yong, Niraj Joshi, Asgerally T Fazleabas, John P Lydon

Faculty, Staff and Students Publications

Although a non-malignant gynecological disorder, endometriosis displays some pathogenic features of malignancy, such as cell proliferation, migration, invasion and adaptation to hypoxia. Current treatments of endometriosis include pharmacotherapy and/or surgery, which are of limited efficacy and often associated with adverse side effects. Therefore, to develop more effective therapies to treat this disease, a broader understanding of the underlying molecular mechanisms that underpin endometriosis needs to be attained. Using immortalized human endometriotic epithelial and stromal cell lines, we demonstrate that the early growth response 1 (EGR1) transcription factor is essential for cell proliferation, migration and invasion, which represent some of the …

Hippo-Taz Signaling Is The Master Regulator Of The Onset Of Triple-Negative Basal-Like Breast Cancers, Hirotoshi Soyama, Miki Nishio, Junji Otani, Toshiko Sakuma, Shintaro Takao, Shigeo Hara, Takaaki Masuda, Koshi Mimori, Shinya Toyokuni, John P Lydon, Kazuwa Nakao, Hiroshi Nishina, Takumi Fukumoto, Tomohiko Maehama, Akira Suzuki

Faculty, Staff and Students Publications

A universal oncogenic driver of basal-like breast cancer (BLBC) has resisted identification. We show that continuous transcriptional coactivator with PDZ-binding motif (TAZ) activation in precancerous murine luminal cells generates luminal cancers that later become BLBCs. Subsequent TP53 alteration, a feature of invasive human BLBCs, accelerates tumor progression. Because BLBC development is inhibited by TAZ inactivation in vivo, our work provides a sound rationale for targeting Hippo-TAZ signaling as therapy for human BLBC. Our mouse model of BLBC represents a powerful tool for evaluating such drugs.

Comparison Of Flash-Free And Conventional Bonding Systems: A Systematic Review And Meta-Analysis, He Wang, Ge Feng, Bo Hu, Haonan Tian, Yunchun Kuang, Tingwei Zhang, Jinlin Song

Faculty, Staff and Student Publications

OBJECTIVES: To review the literature systematically to compare the performance of adhesive precoated flash-free bonding systems with conventional adhesive precoated (APC) and operator-coated (OPC) bonding systems.

MATERIALS AND METHODS: PubMed, Cochrane Library, Web of Science, and Embase were searched for potential eligible studies. Study selection and data collection were conducted independently. Statistical analysis was performed by Review Manager 5.3. The Cochran Q test was used to test heterogeneity in the included studies. Risk of bias was evaluated using Cochrane RoB 2.0 tool for randomized controlled trials.

RESULTS: Six studies were included and the overall risk-of-bias judgment was low risk of …