Hoang Nguyen

Baylor College of Medicine

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Co-Authors

Amy T. Ku

Baylor College of Medicine

Jeffrey Howard

Southwestern Medical Center

Timothy M. Shaver

Menlo School

Qi Miao

Xi'an Jiaotong University

Gloria E. Garcia

Indiana University School of Medicine

Elaine Fuchs

Howard Hughes Medical Institute

Bradley J. Merrill

University of Illinois Chicago

Ajay S Rao

Baylor College of Medicine

Diep Le

Baylor College of Medicine

Christine N Rodriguez

Baylor College of Medicine

Cooperative Institutions

Technology Applications (United States)

162

Baylor College of Medicine

Chinese Academy of Sciences

Zhejiang University

University of Chinese Academy of Sciences

Shanghai Jiao Tong University

Huazhong University of Science and Technology

Sun Yat-sen University

The University of Texas MD Anderson Cancer Center

Peking University

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Research Field

Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses

British Journal of Dermatology (2018)

Jessica C. Sheu Jessica Tran Peter L. Rady H. Dao Stephen K. Tyring

Human polyomaviruses (HPyVs) are small, nonenveloped, double‐stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus – Merkel cell polyomavirus (MCPyV) – six more species have been detected in the skin: trichodysplasia spinulosa‐associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology. In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs. We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV‐associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.

Merkel cell polyomavirus

Polyomavirus Infections

Etiology

Merkel cell

10.1111/bjd.17592

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Citations (27)

Small T‐antigen of the TS‐associated polyomavirus activates factors implicated in the MAPK pathway

Journal of the European Academy of Dermatology and Venereology (2015)

Julie H. Wu Rebecca A. Simonette Hoang Nguyen Peter L. Rady Stephen K. Tyring

10.1111/jdv.13111

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Citations (20)

Function of Wnt/β-catenin in counteracting Tcf3 repression through the Tcf3–β-catenin interaction

Development (2012)

Chun-I Wu Jackson A. Hoffman Brian R. Shy Erin M. Ford Elaine Fuchs

The canonical Wnt/β-catenin signaling pathway classically functions through the activation of target genes by Tcf/Lef–β-catenin complexes. In contrast to β-catenin-dependent functions described for Tcf1, Tcf4 and Lef1, the known embryonic functions for Tcf3 in mice, frogs and fish are consistent with β-catenin-independent repressor activity. In this study, we genetically define Tcf3–β-catenin functions in mice by generating a Tcf3ΔN knock-in mutation that specifically ablates Tcf3–β-catenin. Mouse embryos homozygous for the knock-in mutation (Tcf3ΔN/ΔN) progress through gastrulation without apparent defects, thus genetically proving that Tcf3 function during gastrulation is independent of β-catenin interaction. Tcf3ΔN/ΔN mice were not viable, and several post-gastrulation defects revealed the first in vivo functions of Tcf3–β-catenin interaction affecting limb development, vascular integrity, neural tube closure and eyelid closure. Interestingly, the etiology of defects indicated an indirect role for Tcf3–β-catenin in the activation of target genes. Tcf3 directly represses transcription of Lef1, which is stimulated by Wnt/β-catenin activity. These genetic data indicate that Tcf3–β-catenin is not necessary to activate target genes directly. Instead, our findings support the existence of a regulatory circuit whereby Wnt/β-catenin counteracts Tcf3 repression of Lef1, which subsequently activates target gene expression via Lef1–β-catenin complexes. We propose that the Tcf/Lef circuit model provides a mechanism downstream of β-catenin stability for controlling the strength of Wnt signaling activity during embryonic development.

Beta-catenin

LRP6

LRP5

10.1242/dev.076067

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Citations (105)

TCF7L1 promotes skin tumorigenesis independently of β-catenin through induction of LCN2

eLife (2017)

Amy T. Ku Timothy M. Shaver Ajay S Rao Jeffrey Howard Christine N Rodriguez

The transcription factor TCF7L1 is an embryonic stem cell signature gene that is upregulated in multiple aggressive cancer types, but its role in skin tumorigenesis has not yet been defined. Here we document TCF7L1 upregulation in skin squamous cell carcinoma (SCC) and demonstrate that TCF7L1 overexpression increases tumor incidence, tumor multiplicity, and malignant progression in the chemically induced mouse model of skin SCC. Additionally, we show that downregulation of TCF7L1 and its paralogue TCF7L2 reduces tumor growth in a xenograft model of human skin SCC. Using separation-of-function mutants, we show that TCF7L1 promotes tumor growth, enhances cell migration, and overrides oncogenic RAS-induced senescence independently of its interaction with β-catenin. Through transcriptome profiling and combined gain- and loss-of-function studies, we identified LCN2 as a major downstream effector of TCF7L1 that drives tumor growth. Our findings establish a tumor-promoting role for TCF7L1 in skin and elucidate the mechanisms underlying its tumorigenic capacity.

10.7554/elife.23242

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Citations (23)

SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair

Nature Communications (2019)

Qi Miao Matthew C. Hill Fengju Chen Qianxing Mo Amy T. Ku

Abstract Tissue injury induces changes in cellular identity, but the underlying molecular mechanisms remain obscure. Here, we show that upon damage in a mouse model, epidermal cells at the wound edge convert to an embryonic-like state, altering particularly the cytoskeletal/extracellular matrix (ECM) components and differentiation program. We show that SOX11 and its closest relative SOX4 dictate embryonic epidermal state, regulating genes involved in epidermal development as well as cytoskeletal/ECM organization. Correspondingly, postnatal induction of SOX11 represses epidermal terminal differentiation while deficiency of Sox11 and Sox4 accelerates differentiation and dramatically impairs cell motility and re-epithelialization. Amongst the embryonic genes reactivated at the wound edge, we identify fascin actin-bundling protein 1 (FSCN1) as a critical direct target of SOX11 and SOX4 regulating cell migration. Our study identifies the reactivated embryonic gene program during wound repair and demonstrates that SOX11 and SOX4 play a central role in this process.

10.1038/s41467-019-11880-9

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Citations (76)

Runx1 Role in Epithelial and Cancer Cell Proliferation Implicates Lipid Metabolism and Scd1 and Soat1 Activity

Stem Cells (2018)

Prachi Jain Mary Nattakom David Holowka Dong Hao Wang J. Thomas Brenna

The role of lipid metabolism in epithelial stem cell (SC) function and carcinogenesis is poorly understood. The transcription factor Runx1 is known to regulate proliferation in mouse epithelial hair follicle (HF) SCs in vivo and in several mouse and human epithelial cancers. We found a novel subset of in vivo Runx1 HFSC target genes related to lipid metabolism and demonstrated changes in distinct classes of lipids driven by Runx1. Inhibition of lipid-enzymes Scd1 and Soat1 activity synergistically reduces proliferation of mouse skin epithelial cells and of human skin and oral squamous cell carcinoma cultured lines. Varying Runx1 levels induces changes in skin monounsaturated fatty acids (e.g., oleate, a product of Scd1) as shown by our lipidome analysis. Furthermore, varying Runx1 levels, the inhibition of Scd1, or the addition of Scd1-product oleate, individually affects the plasma membrane organization (or fluidity) in mouse keratinocytes. These factors also affect the strength of signal transduction through the membranes for Wnt, a pathway that promotes epithelial (cancer) cell proliferation and HFSC activation. Our working model is that HFSC factor Runx1 modulates the fatty acid production, which affects membrane organization, facilitating signal transduction for rapid proliferation of normal and cancer epithelial cells. Stem Cells 2018;36:1603-1616.

10.1002/stem.2868

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Citations (29)

Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments

Nature Reviews Molecular Cell Biology (2015)

Margaret A. Goodell Hoang Nguyen Noah F. Shroyer

Cell type

Intestinal epithelium

Stem cell marker

10.1038/nrm3980

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Citations (167)

Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms

Cell stem cell (2019)

Xing Wei Li Zhang Zhicheng Zhou Oh‐Joon Kwon Yiqun Zhang

LRP6

WNT3A

LRP5

WNT5A

Beta-catenin

10.1016/j.stem.2019.03.010

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Citations (57)

Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18

Development (2013)

Erin Leishman Jeffrey Howard Gloria E. Garcia Qi Miao Amy T. Ku

Hair follicles cyclically degenerate and regenerate throughout adult life and require regular stem cell activation to drive the cycle. In the resting phase of the hair cycle, hair follicle stem cells are maintained in a quiescent state until they receive signals to proliferate. We found that the forkhead transcription factor Foxp1 is crucial for maintaining the quiescence of hair follicle stem cells. Loss of Foxp1 in skin epithelial cells leads to precocious stem cell activation, resulting in drastic shortening of the quiescent phase of the hair cycle. Conversely, overexpression of Foxp1 in keratinocytes prevents cell proliferation by promoting cell cycle arrest. Finally, through both gain- and loss-of-function studies, we identify fibroblast growth factor 18 (Fgf18) as the key downstream target of Foxp1. We show that exogenously supplied FGF18 can prevent the hair follicle stem cells of Foxp1 null mice from being prematurely activated. As Fgf18 controls the length of the quiescent phase and is a key downstream target of Foxp1, our data strongly suggest that Foxp1 regulates the quiescent stem cell state in the hair follicle stem cell niche by controlling Fgf18 expression.

Hair cycle

10.1242/dev.097477

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Citations (79)

Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2

Nature Communications (2014)

Qi Miao Amy T. Ku Yudai Nishino Jeffrey Howard Ajay S Rao

10.1038/ncomms5088

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Citations (67)