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| 1 | Adenovirus-mediated gene delivery:Potential applications for gene and cell-based therapies in the new era of personalized medicine显示文摘With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology,it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies.Despite numerous setbacks,efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases.It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies.There has been a long-lasting interest in using viral vectors,especially adenoviral vectors,to deliver therapeutic genes for the past two decades.Among all currently available viral vectors,adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types.The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development.In fact,among over 2000 gene therapy clinical trials approved worldwide since 1989,a significant portion of the trials have utilized adenoviral vectors.This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors,including adenoviral biology,approaches to engineering adenoviral vectors,and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment,vaccination and regenerative medicine.Current challenges and future directions regarding the use of adenoviral vectors are also discussed.It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine. | Cody S.Lee Elliot S.Bishop Ruyi Zhang Xinyi Yu Evan M.Farina Shujuan Yan Chen Zhao Zongyue Zeng Yi Shu Xingye Wu Jiayan Lei Yasha Li Wenwen Zhang Chao Yang Ke Wu Ying Wu Sherwin Ho Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Russell R.Reid Tong-Chuan He | 2017 | Genes & Diseases2017，4，2： | 19 |
| 2 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 3 | Neural EGF-like protein 1(NELL-1):Signaling crosstalk in mesenchymal stem cells and applications in regenerative medicine显示文摘Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant morbidity.The differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth factors.Neural EGF Like-Like molecule 1(NELL-1)is a secreted glycoprotein that has proven,both in vitro and in vivo,to be a potent osteo-inductive factor.Furthermore,it has been shown to repress adipogenic differentiation and inflammation.NELL-1 can work synergistically with other osteogenic factors such as Bone Morphogenic Protein(BMP)2 and9,and has shown promise for use in tissue engineering and as a systemically administered drug for the treatment of osteoporosis.Here we provide a comprehensive up-to-date review on the molecular signaling cascade of NELL-1 in mesenchymal stem cells and potential applications in bone regenerative engineering. | Mikhail Pakvasa Alex Alverdy Sami Mostafa Eric Wang Lucy Fu Alexander Li Leonardo Oliveira Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Tong-Chuan He Guillermo A.Ameer Russell R.Reid | 2017 | Genes & Diseases2017，4，3： | 13 |
| 4 | Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)显示文摘Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and myocytes.MSCs represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult tissues.At least 14 BMPs have been identified in mammals.Different BMPs exert distinct but overlapping biological functions.Through a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of MSCs.Nonetheless,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully elucidated.Here,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of BMPs.Hierarchical clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 cluster.We also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase pathway.Furthermore,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR pathways.While the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs. | Linghuan Zhang Qing Luo Yi Shu Zongyue Zeng Bo Huang Yixiao Feng Bo Zhang Xi Wang Yan Lei Zhenyu Ye Ling Zhao Daigui Cao Lijuan Yang Xian Chen Bin Liu William Wagstaff Russell R*Reid Hue H*Luu Rex C*Haydon Michael J*Lee Jennifer Moriatis Wolf Zhou Fu Tong-Chuan He Quan Kang | 2019 | Genes & Diseases2019，6，3： | 11 |
| 5 | 3-D bioprinting technologies in tissue engineering and regenerative medicine:Current and future trends显示文摘Advances in three-dimensional(3D)printing have increased feasibility towards the synthesis of living tissues.Known as 3D bioprinting,this technology involves the precise layering of cells,biologic scaffolds,and growth factors with the goal of creating bioidentical tissue for a variety of uses.Early successes have demonstrated distinct advantages over conventional tissue engineering strategies.Not surprisingly,there are current challenges to address before 3D bioprinting becomes clinically relevant.Here we provide an overview of 3D bioprinting technology and discuss key advances,clinical applications,and current limitations.While 3D bioprinting is a relatively novel tissue engineering strategy,it holds great potential to play a key role in personalized medicine. | Elliot S.Bishop Sami Mostafa Mikhail Pakvasa Hue H.Luu Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He Russell R.Reid | 2017 | Genes & Diseases2017，4，4： | 10 |
| 6 | Highly expressed BMP9/GDF2 in postnatal mouse liver and lungs may account for its pleiotropic effects on stem cell differentiation,angiogenesis,tumor growth and metabolism显示文摘Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis.However,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed.Here,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice.By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult placenta.We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages.We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older mice.Interestingly,Bmp9 was only expressed at low to modest levels in developing bones.BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs.Furthermore,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues.However,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic fashion.Thus,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood. | Wei Liu Zhongliang Deng Zongyue Zeng Jiaming Fan Yixiao Feng Xi Wang Daigui Cao Bo Zhang Lijuan Yang Bin Liu Mikhail Pakvasa William Wagstaff Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Huiming Ding Yongtao Zhang Changchun Niu Rex C.Haydon Hue H.Luu Jennifer Moriatis Wolf Michael J.Lee Wei Huang Tong-Chuan He Yulong Zou | 2020 | Genes & Diseases2020，7，2： | 9 |
| 7 | Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference显示文摘Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics. | Shujuan Yan Ruyi Zhang Ke Wu Jing Cui Shifeng Huang Xiaojuan Ji Liping An Chengfu Yuan Cheng Gong Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Bo Liu Rex C.Haydon Michael J.Lee Russell R.Reid Jennifer Moriatis Wolf Qiong Shi Hue H.Luu Tong-Chuan He Yaguang Weng | 2018 | Genes & Diseases2018，5，2： | 8 |
| 8 | Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells(MSCs)显示文摘Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes.Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries.Bone morphogenetic protein 2(BMP2)induces effective chondrogenesis of mesenchymal stem cells(MSCs)and can thus be explored as a potential therapeutic agent for cartilage defect repair.However,BMP2 also induces robust endochondral ossification.Although the precise mechanisms through which BMP2 governs the divergence of chondrogenesis and osteogenesis remain to be fully understood,blocking endochondral ossification during BMP2-induced cartilage formation may have practical significance for cartilage tissue engineering.Here,we investigate the role of Sox9-donwregulated Smad7 in BMP2-induced chondrogenic differentiation of MSCs.We find that overexpression of Sox9 leads to a decrease in BMP2-induced Smad7 expression in MSCs.Sox9 inhibits BMP2-induced expression of osteopontin while enhancing the expression of chondrogenic marker Col2a1 in MSCs.Forced expression of Sox9 in MSCs promotes BMP2-induced chondrogenesis and suppresses BMP2-induced endochondral ossification.Constitutive Smad7 expression inhibits BMP2-induced chondrogenesis in stem cell implantation assay.Mouse limb explant assay reveals that Sox9 expands BMP2-stimulated chondrocyte proliferating zone while Smad7 promotes BMP2-intitated hypertrophic zone of the growth plate.Cell cycle analysis indicates that Smad7 induces significant early apoptosis in BMP2-stimulated MSCs.Taken together,our results strongly suggest that Sox9 may facilitate BMP2-induced chondrogenesis by downregulating Smad7,which can be exploited for effective cartilage tissue engineering. | Chen Zhao Wei Jiang Nian Zhou Junyi Liao Mingming Yang Ning Hu Xi Liang Wei Xu Hong Chen Wei Liu Lewis L.Shi Leonardo Oliveira Jennifer Moriatis Wolf Sherwin Ho Aravind Athiviraham H.M.Tsai Tong-Chuan He Wei Huang | 2017 | Genes & Diseases2017，4，4： | 7 |
| 9 | Stem cell therapy for chronic skin wounds in the era of personalized medicine:From bench to bedside显示文摘With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care. | Elam Coalson Elliot Bishop Wei Liu Yixiao Feng Mia Spezia Bo Liu Yi Shen Di Wu Scott Du Alexander J.Li Zhenyu Ye Ling Zhao Daigui Cao Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Rex C.Haydon Lewis Shi Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He Russell R.Reid | 2019 | Genes & Diseases2019，6，4： | 6 |
| 10 | Notch signaling:Its essential roles in bone and craniofacial development显示文摘Notch is a cellecell signaling pathway that is involved in a host of activities including development,oncogenesis,skeletal homeostasis,and much more.More specifically,recent research has demonstrated the importance of Notch signaling in osteogenic differentiation,bone healing,and in the development of the skeleton.The craniofacial skeleton is complex and understanding its development has remained an important focus in biology.In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton,skull,and face develop.We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system,and what importance it may play in the future. | Mikhail Pakvasa Pranav Haravu Michael Boachie-Mensah Alonzo Jones Elam Coalson Junyi Liao Zongyue Zeng Di Wu Kevin Qin Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Yongtao Zhang Changchun Niu Meng Wu Xia Zhao Hao Wang Linjuan Huang Deyao Shi Qing Liu Na Ni Kai Fu Michael J.Lee Jennifer Moriatis Wolf Aravind Athiviraham Sherwin S.Ho Tong-Chuan He Kelly Hynes Jason Strelzow Mostafa El Dafrawy Russell R.Reid | 2021 | Genes & Diseases2021，8，1： | 4 |
| 11 | Lateral Epi- eondylitis: Review and Current Concepts 显示文摘 | Frances Faro Jennifer Moriatis Wolf | 2007 | The Journal of Hand Surgery2007，8，32： | 1 |
| 12 | Epidemiology of Lateral and Medial Epicondylitis in a Military Population显示文摘 | Wolf Jennifer Moriatis Mountcastle Sally Burks Robert Sturdivant Rodney X Owens Brett D | 2010 | Military Medicine2010，，5： | 1 |
| 13 | Corrigendum to “Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells (MSCs)” [Genes & Diseases 4 (2017) 229–239]显示文摘The authors regret having image assembly errors in Figure 1A and Figure 3A.Specifically,in Figure 1A,the images for'C3H10T1/2',''BMP2'and'Sox9'were erroneously duplicated with the images from an irrelevant experiment that was conducted at the same time.In Figure 3A,the images for'Col2a1'and'β-actin'were erroneously duplicated with the images from an irrelevant experiment that was conducted at the same time. | Chen Zhao Wei Jiang Nian Zhou Junyi Liao Mingming Yang Ning Hu Xi Liang Wei Xu Hong Chen Wei Liu Lewis L. Shi Leonardo Oliveira Jennifer Moriatis Wolf Sherwin Ho Aravind Athiviraham H.M. Tsai Tong-Chuan He Wei Huang | 2023 | Genes & Diseases2023，10，2： | 0 |
| 14 | Corrigendum to “Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference” [Genes & Diseases 5(2018):172–184]显示文摘The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for 'AdsimB9-4 only'group was erroneously duplicated with an overlapping image from the'AdRFp'group;and the image for'AdsimB9-1+BMP9'groupwas erroneouslyduplicatedwithan overlapping image from'AdsimB9-8+BMP9'group.In Figure 4Apanel a,the images for'BMP9'group and 'BMP9+simB9-4'group were erroneously duplicated with an overlapping image from'simB9-4'group.In Figure 5A,the image for'BMP9+simB9-4/Day3'group was erroneously duplicated with an overlapping image from'BMP9+simB9-7/Day3'group;and the image for'BMP9+simB9-4/Day5'group was erroneously duplicated with an overlapping image from an unrelated experiment.In Figure 6B,the image for'BMP9+simB9-7/Day 11'group was erroneously duplicated with an overlapping image from the'BMP9+simB9-4/Day 11'group. | Shujuan Yan Ruyi Zhang Ke Wu Jing Cui Shifeng Huang Xiaojuan Ji Liping An Chengfu Yuan Cheng Gong Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Bo Liu Rex C. Haydon Michael J. Lee Russell R. Reid Jennifer Moriatis Wolf Qiong Shi Hue H. Luu Tong-Chuan He Yaguang Weng | 2023 | Genes & Diseases2023，10，2： | 0 |
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