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Author Chad M Vezina

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A Uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate.

Hannah Ruetten, Jaskiran K Sandhu, Brett Mueller, Peiqing Wang, Helen L Zhang, Kyle A Wegner, Mark T Cadena, Simran K Sandhu, Lisa L Abler, Jonathan Zhu, Chelsea A O'Driscoll, Britta Chelgren, Zunyi Wang, Tian Shen, Jonathan Barasch, Dale E Bjorling, Chad M Vezina,

Bacterial infection is one known etiology of prostatic inflammation. Prostatic inflammation is associated with prostatic collagen accumulation and both are linked to progressive lower urinary tract symptoms in men. We characterized a model of prostatic inflammation utilizing transurethral instillations of E. coli UTI89 in C57BL/6J male mice with the goal ... Read more >>

Am J Physiol Renal Physiol (American journal of physiology. Renal physiology)
[2020, :]

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An immunohistochemical prostate cell identification key indicates that aging shifts procollagen 1A1 production from myofibroblasts to fibroblasts in dogs prone to prostate-related urinary dysfunction.

Hannah Ruetten, Clara Cole, Marlyse Wehber, Kyle A Wegner, Nicholas M Girardi, Nelson T Peterson, Brandon R Scharpf, Michael F Romero, Michael W Wood, Sara A Colopy, Dale E Bjorling, Chad M Vezina,

BACKGROUND:The identity and spatial distribution of prostatic cell types has been determined in humans but not in dogs, even though aging- and prostate-related voiding disorders are common in both species and mechanistic factors, such as prostatic collagen accumulation, appear to be shared between species. In this publication we characterize the ... Read more >>

PLoS One (PloS one)
[2020, 15(7):e0232564]

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Urethral luminal epithelia are castration-insensitive cells of the proximal prostate.

Diya B Joseph, Gervaise H Henry, Alicia Malewska, Nida S Iqbal, Hannah M Ruetten, Anne E Turco, Lisa L Abler, Simran K Sandhu, Mark T Cadena, Venkat S Malladi, Jeffrey C Reese, Ryan J Mauck, Jeffrey C Gahan, Ryan C Hutchinson, Claus G Roehrborn, Linda A Baker, Chad M Vezina, Douglas W Strand,

BACKGROUND:Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. ... Read more >>

Prostate (The Prostate)
[2020, 80(11):872-884]

Cited: 1 time

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GLI3 resides at the intersection of hedgehog and androgen action to promote male sex differentiation.

Anbarasi Kothandapani, Samantha R Lewis, Jessica L Noel, Abbey Zacharski, Kyle Krellwitz, Anna Baines, Stephanie Winske, Chad M Vezina, Elena M Kaftanovskaya, Alexander I Agoulnik, Emily M Merton, Martin J Cohn, Joan S Jorgensen,

Urogenital tract abnormalities are among the most common congenital defects in humans. Male urogenital development requires Hedgehog-GLI signaling and testicular hormones, but how these pathways interact is unclear. We found that Gli3XtJ mutant mice exhibit cryptorchidism and hypospadias due to local effects of GLI3 loss and systemic effects of testicular ... Read more >>

PLoS Genet (PLoS genetics)
[2020, 16(6):e1008810]

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Prostatic osteopontin expression is associated with symptomatic benign prostatic hyperplasia.

Petra Popovics, Wisam N Awadallah, Sarah E Kohrt, Thomas C Case, Nicole L Miller, Emily A Ricke, Wei Huang, Marisol Ramirez-Solano, Qi Liu, Chad M Vezina, Robert J Matusik, William A Ricke, Magdalena M Grabowska,

BACKGROUND:Male lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We ... Read more >>

Prostate (The Prostate)
[2020, 80(10):731-741]

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Radiation cystitis modeling: A comparative study of bladder fibrosis radio-sensitivity in C57BL/6, C3H, and BALB/c mice.

Bernadette M M Zwaans, Kyle A Wegner, Sarah N Bartolone, Chad M Vezina, Michael B Chancellor, Laura E Lamb,

A subset of patients receiving radiation therapy for pelvic cancer develop radiation cystitis, a complication characterized by mucosal cell death, inflammation, hematuria, and bladder fibrosis. Radiation cystitis can reduce bladder capacity, cause incontinence, and impair voiding function so severely that patients require surgical intervention. Factors influencing onset and severity of ... Read more >>

Physiol Rep (Physiological reports)
[2020, 8(4):e14377]

Cited: 2 times

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Cyp1b1 directs Srebp-mediated cholesterol and retinoid synthesis in perinatal liver; Association with retinoic acid activity during fetal development.

Meghan Maguire, Michele Campaigne Larsen, Chad M Vezina, Loredana Quadro, Youn-Kyung Kim, Sherry A Tanumihardjo, Colin R Jefcoate,

BACKGROUND:Cytochrome P450 1b1 (Cyp1b1) deletion and dietary retinol deficiency during pregnancy (GVAD) affect perinatal liver functions regulated by Srebp. Cyp1b1 is not expressed in perinatal liver but appears in the E9.5 embryo, close to sites of retinoic acid (RA) signaling. HYPOTHESIS:Parallel effects of Cyp1b1 and retinol on postnatal Srebp derive ... Read more >>

PLoS One (PloS one)
[2020, 15(2):e0228436]

Cited: 1 time

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Synthesis and biological evaluation of FICZ analogues as agonists of aryl hydrocarbon receptor.

Hao Wu, Binkai Liu, Ka Yang, Gabrielle N Winston-McPherson, Eric D Leisten, Chad M Vezina, William A Ricke, Richard E Peterson, Weiping Tang,

The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor involved in multiple biological processes including immune cell differentiation, intestinal function and inflammation. Based on the scaffold of naturally occurring AhR ligand 6-formylindolo (3,2-b) carbazole (FICZ, 2), a series of analogues has been designed, synthesized and evaluated by cell-based ... Read more >>

Bioorg Med Chem Lett (Bioorganic & medicinal chemistry letters)
[2020, 30(5):126959]

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Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: urethral histology.

Hannah Ruetten, Kyle A Wegner, Conner L Kennedy, Anne Turco, Helen L Zhang, Peiqing Wang, Jaskiran Sandhu, Simran Sandhu, Jacquelyn Morkrid, Zunyi Wang, Jill Macoska, Richard E Peterson, Dale E Bjorling, William A Ricke, Paul C Marker, Chad M Vezina,

The National Institutes of Health leveled new focus on sex as a biological variable with the goal of understanding sex-specific differences in health and physiology. We previously published a functional assessment of the impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology (Ruetten H, Wegner KA, Zhang ... Read more >>

Am J Physiol Renal Physiol (American journal of physiology. Renal physiology)
[2020, 318(3):F617-F627]

Cited: 0 times

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Loss-of-Function Variants in PPP1R12A: From Isolated Sex Reversal to Holoprosencephaly Spectrum and Urogenital Malformations.

Joel J Hughes, Ebba Alkhunaizi, Paul Kruszka, Louise C Pyle, Dorothy K Grange, Seth I Berger, Katelyn K Payne, Diane Masser-Frye, Tommy Hu, Michelle R Christie, Nancy J Clegg, Joshua L Everson, Ariel F Martinez, Laurence E Walsh, Emma Bedoukian, Marilyn C Jones, Catharine Jean Harris, Korbinian M Riedhammer, Daniela Choukair, Patricia Y Fechner, Meilan M Rutter, Sophia B Hufnagel, Maian Roifman, Gad B Kletter, Emmanuele Delot, Eric Vilain, Robert J Lipinski, Chad M Vezina, Maximilian Muenke, David Chitayat,

In two independent ongoing next-generation sequencing projects for individuals with holoprosencephaly and individuals with disorders of sex development, and through international research collaboration, we identified twelve individuals with de novo loss-of-function (LoF) variants in protein phosphatase 1, regulatory subunit 12a (PPP1R12A), an important developmental gene involved in cell migration, adhesion, ... Read more >>

Am J Hum Genet (American journal of human genetics)
[2020, 106(1):121-128]

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Insight and Resources From a Study of the "Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology.

Hannah Ruetten, Kyle A Wegner, Helen L Zhang, Peiqing Wang, Jaskiran Sandhu, Simran Sandhu, Jacquelyn Morkrid, Brett Mueller, Zunyi Wang, Jill Macoska, Richard E Peterson, Dale E Bjorling, William A Ricke, Paul C Marker, Chad M Vezina,

The purpose of this symposium report is to summarize information from a session 3 oral presentation at the Society of Toxicologic Pathology Annual Symposium in Raleigh, North Carolina. Mice are genetically tractable and are likely to play an important role in elucidating environmental, genetic, and aging-related mechanisms of urinary dysfunction ... Read more >>

Toxicol Pathol (Toxicologic pathology)
[2019, 47(8):1038-1042]

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Prostate epithelial-specific expression of activated PI3K drives stromal collagen production and accumulation.

Kyle A Wegner, Brett R Mueller, Christopher J Unterberger, Enrique J Avila, Hannah Ruetten, Anne E Turco, Steven R Oakes, Nicholas M Girardi, Richard B Halberg, Steven M Swanson, Paul C Marker, Chad M Vezina,

We genetically engineered expression of an activated form of P110 alpha, the catalytic subunit of PI3K, in mouse prostate epithelium to create a mouse model of direct PI3K activation (Pbsn-cre4Prb;PI3KGOF/+ ). We hypothesized that direct activation would cause rapid neoplasia and cancer progression. Pbsn-cre4Prb;PI3KGOF/+ mice developed widespread prostate intraepithelial hyperplasia, ... Read more >>

J Pathol (The Journal of pathology)
[2020, 250(2):231-242]

Cited: 1 time

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Sox9 in mouse urogenital sinus epithelium mediates elongation of prostatic buds and expression of genes involved in epithelial cell migration.

Andrew J Schneider, Joseph Gawdzik, Chad M Vezina, Tracie R Baker, Richard E Peterson,

Previous studies identified Sox9 as a critical mediator of prostate development but the precise stage when Sox9 acts had not been determined. A genetic approach was used to delete Sox9 from mouse urogenital sinus epithelium (UGE) prior to prostate specification. All prostatic bud types (anterior, dorsolateral and ventral) were stunted ... Read more >>

Gene Expr Patterns (Gene expression patterns : GEP)
[2019, 34:119075]

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Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment.

Hannah Ruetten, Kyle A Wegner, Helen L Zhang, Peiqing Wang, Jaskiran Sandhu, Simran Sandhu, Brett Mueller, Zunyi Wang, Jill Macoska, Richard E Peterson, Dale E Bjorling, William A Ricke, Paul C Marker, Chad M Vezina,

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically ... Read more >>

Am J Physiol Renal Physiol (American journal of physiology. Renal physiology)
[2019, 317(4):F996-F1009]

Cited: 0 times

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Void sorcerer: an open source, open access framework for mouse uroflowmetry.

Zunyi Wang, Emmanuel Contreras Guzman, Amit Nimunkar, Kimberly P Keil, Chad M Vezina, William A Ricke, Jill Macoska, Dale E Bjorling,

Observational and experimental studies of rodent voiding behaviors have greatly contributed to our understanding of lower urinary tract function including the complex social, environmental, and internal stimuli that affect voiding in health and models of disease. Void spot assays (VSA), cystometry (awake or anesthetized), and uroflowmetry are techniques commonly used ... Read more >>

(American journal of clinical and experimental urology)
[2019, 7(3):170-177]

Cited: 2 times

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A temporal and spatial map of axons in developing mouse prostate.

Anne E Turco, Mark T Cadena, Helen L Zhang, Jaskiran K Sandhu, Steven R Oakes, Thrishna Chathurvedula, Richard E Peterson, Janet R Keast, Chad M Vezina,

Prostate autonomic and sensory axons control glandular growth, fluid secretion, and smooth muscle contraction and are remodeled during cancer and inflammation. Morphogenetic signaling pathways reawakened during disease progression may drive this axon remodeling. These pathways are linked to proliferative activities in prostate cancer and benign prostate hyperplasia. However, little is ... Read more >>

Histochem Cell Biol (Histochemistry and cell biology)
[2019, 152(1):35-45]

Cited: 1 time

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Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate.

Kyle A Wegner, Vatsal Mehta, Jeanette A Johansson, Brett R Mueller, Kimberly P Keil, Lisa L Abler, Paul C Marker, M Mark Taketo, Denis J Headon, Chad M Vezina,

Beta-catenin (CTNNB1) directs ectodermal appendage spacing by activating ectodysplasin A receptor (EDAR) transcription, but whether CTNNB1 acts by a similar mechanism in the prostate, an endoderm-derived tissue, is unclear. Here we examined the expression, function, and CTNNB1 dependence of the EDAR pathway during prostate development. In situ hybridization studies reveal ... Read more >>

Biol Open (Biology open)
[2019, 8(3):]

Cited: 0 times

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Epithelial DNA methyltransferase-1 regulates cell survival, growth and maturation in developing prostatic buds.

Diya B Joseph, Anoop S Chandrashekar, Lisa L Abler, Li-Fang Chu, James A Thomson, Chad M Vezina,

DNA methyltransferase 1 (DNMT1) is required for embryogenesis but roles in late forming organ systems including the prostate, which emerges from the urethral epithelium, have not been fully examined. We used a targeted genetic approach involving a Shhcre recombinase to demonstrate requirement of epithelial DNA methyltransferase-1 (Dnmt1) in mouse prostate ... Read more >>

Dev Biol (Developmental biology)
[2019, 447(2):157-169]

Cited: 1 time

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A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

Gervaise H Henry, Alicia Malewska, Diya B Joseph, Venkat S Malladi, Jeon Lee, Jose Torrealba, Ryan J Mauck, Jeffrey C Gahan, Ganesh V Raj, Claus G Roehrborn, Gary C Hon, Malcolm P MacConmara, Jeffrey C Reese, Ryan C Hutchinson, Chad M Vezina, Douglas W Strand,

A comprehensive cellular anatomy of normal human prostate is essential for solving the cellular origins of benign prostatic hyperplasia and prostate cancer. The tools used to analyze the contribution of individual cell types are not robust. We provide a cellular atlas of the young adult human prostate and prostatic urethra using ... Read more >>

Cell Rep (Cell reports)
[2018, 25(12):3530-3542.e5]

Cited: 16 times

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Development of the human prostate.

Gerald R Cunha, Chad M Vezina, Dylan Isaacson, William A Ricke, Barry G Timms, Mei Cao, Omar Franco, Laurence S Baskin,

This paper provides a detailed compilation of human prostatic development that includes human fetal prostatic gross anatomy, histology, and ontogeny of selected epithelial and mesenchymal differentiation markers and signaling molecules throughout the stages of human prostatic development: (a) pre-bud urogenital sinus (UGS), (b) emergence of solid prostatic epithelial buds from ... Read more >>

Differentiation (Differentiation; research in biological diversity)
[2018, 103:24-45]

Cited: 9 times

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Peripartum Fluoxetine Reduces Maternal Trabecular Bone After Weaning and Elevates Mammary Gland Serotonin and PTHrP.

Samantha R Weaver, Hannah P Fricke, Cynthia Xie, Robert J Lipinski, Chad M Vezina, Julia F Charles, Laura L Hernandez,

Selective serotonin reuptake inhibitors (SSRIs) have been linked to osteopenia and fracture risk; however, their long-term impact on bone health is not well understood. SSRIs are widely prescribed to pregnant and breastfeeding women who might be at particular risk of bone pathology because lactation is associated with considerable maternal bone ... Read more >>

Endocrinology (Endocrinology)
[2018, 159(8):2850-2862]

Cited: 2 times

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In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells.

Diya B Joseph, Anoop S Chandrashekar, Lisa L Abler, Li-Fang Chu, James A Thomson, Cathy Mendelsohn, Chad M Vezina,

The bladder's remarkable regenerative capacity had been thought to derive exclusively from its own progenitors. While examining consequences of DNA methyltransferase 1 (Dnmt1) inactivation in mouse embryonic bladder epithelium, we made the surprising discovery that Wolffian duct epithelial cells can support bladder regeneration. Conditional Dnmt1 inactivation in mouse urethral and ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2018, 115(33):8394-8399]

Cited: 3 times

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High collagen density augments mTOR-dependent cancer stem cells in ERα+ mammary carcinomas, and increases mTOR-independent lung metastases.

Michael P Shea, Kathleen A O'Leary, Kyle A Wegner, Chad M Vezina, Linda A Schuler,

Metastatic estrogen receptor alpha positive (ERα+) cancers account for most breast cancer mortality. Cancer stem cells (CSCs) and dense/stiff extracellular matrices are implicated in aggression and therapy resistance. We examined this interplay and response to mTOR inhibition using ERα+ adenocarcinomas from NRL-PRL females in combination with Col1a1tmJae/+ (mCol1a1) mice, which ... Read more >>

Cancer Lett (Cancer letters)
[2018, 433:1-9]

Cited: 6 times

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Prostatic collagen architecture in neutered and intact canines.

Hannah Ruetten, Kyle A Wegner, Michael F Romero, Michael W Wood, Paul C Marker, Douglas Strand, Sara A Colopy, Chad M Vezina,

BACKGROUND:Prostate stiffness and increased collagen content both associate with the presence of urinary symptoms in men but mechanisms responsible, including impact of age and androgens, are unknown. Dogs develop prostate-related urinary dysfunction similar to humans, but mechanisms are also unknown. Mice have been used to examine how prostatic collagen accumulation ... Read more >>

Prostate (The Prostate)
[2018, 78(11):839-848]

Cited: 3 times

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An immunohistochemical identification key for cell types in adult mouse prostatic and urethral tissue sections.

Kyle A Wegner, Mark T Cadena, Ryan Trevena, Anne E Turco, Adam Gottschalk, Richard B Halberg, Jinjin Guo, Jill A McMahon, Andrew P McMahon, Chad M Vezina,

Though many methods can be used to identify cell types contained in complex tissues, most require cell disaggregation and destroy information about where cells reside in relation to their microenvironment. Here, we describe a polytomous key for cell type identification in intact sections of adult mouse prostate and prostatic urethra. ... Read more >>

PLoS One (PloS one)
[2017, 12(11):e0188413]

Cited: 4 times

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