Junwang Xu, PhD
Assistant Professor, Surgery-Peds Surgery

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Internships:
  • University of Pennsylvania Program (2005)
  • UMDNJ-New Jersey Medical School Program (2002)
Languages: English
Department: Surgery-Peds Surgery

Professional Titles

  • Assistant Professor, Surgery-Peds Surgery
  • Assistant Professor

Recognition & Awards

  • Junior Faculty Travel Award, Wound Healing Society (2014)
  • American Heart Association Award for Postdoctoral Fellowship, American Heart Association (2007)

Research Interests

• Complications of diabetes, such as impaired wound healing, represent a major clinical problem and result in significant morbidities and mortality. For example, diabetic wound healing complications are responsible for over 60% of all non-traumatic amputations and result in significant healthcare expenses. My team was the first to implicate dysregulation of microRNAs in the pathogenesis of the diabetic wound healing impairment. In particular, we demonstrated that the chronic inflammation seen in diabetic wounds was associated with decreased production of microRNA-146a, which acts as a molecular brake on the inflammatory response, resulting in increased production of downstream pro-inflammatory cytokines. In addition, we also demonstrated that the impaired angiogenesis seen in diabetic wounds was associated with increased expression of microRNA-15b, a key suppressor of angiogenesis. In related experiments, we also examined the mechanisms of mesenchymal stem cell (MSC) mediated correction of the diabetic wound healing impairment. We demonstrated that correction of the diabetic wound healing impairment with MSC was associated with correction of dysregulated expression of microRNA-146a and microRNA-15b. Our team continues to examine the role dysregulated microRNAs play in the diabetic wound healing impairment to develop potential therapeutic and diagnostic applications to improve diabetic wound healing. • After establishing my independent laboratory at the University of Colorado, My lab did the pioneer studies in understanding the role of lncRNA in wound healing. Lethe, an anti-inflammatory lncRNA, has been studied in our lab, and we provide the first evidence that lncRNA Lethe is involved in the regulation of ROS production in macrophages through modulation of NOX2 gene expression via NF?B signaling. We also found that lncRNA GAS5 (Growth Arrest-Specific 5) was up-regulated in diabetic wounds, and the persistence of the proinflammatory macrophage phenotype in diabetic wounds was mediated partly by GAS5/STAT1 pathway. Overexpression of GAS5 induced STAT1 gene expression in a dose-response pattern. Knockdown STAT1 resulted in significantly increased gene expression of M1 macrophage markers (iNOS, TNFa, and IL1-Beta), while demonstrating no change M2 macrophage markers (Arg1, and Mrc1). These findings provide evidence that the lncRNA GAS5 promotes proinflammatory macrophage phenotype through the cascade of GAS5/miR-222/STAT1. Furthermore, these results suggest a novel link between lncRNA and macrophage phenotype in diabetic wounds.

Publications

  • Hu J, Zhang L, Liechty C, Zgheib C, Hodges MM, Liechty KW, Xu J. Long non-coding RNA GAS5 regulates macrophage polarization and diabetic wound healing. J Invest Dermatol. 2020 Jan 28. [Epub ahead of print] PubMed PMID: 32004569
  • Hilton SA, Dewberry LC, Hodges MM, Hu J, Xu J, Liechty KW, Zgheib C. Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy. PLoS One. 2019;14(7):e0218536. PubMed PMID: 31306414
  • Hodges MM, Zgheib C, Xu J, Hu J, Dewberry LC, Hilton SA, Allukian MW, Gorman JH 3rd, Gorman RC, Liechty KW. Differential Expression of Transforming Growth Factor-ß1 Is Associated With Fetal Regeneration After Myocardial Infarction. Ann Thorac Surg. 2019 Jul;108(1):59-66. PubMed PMID: 30690019
  • Zgheib C, Hilton SA, Dewberry LC, Hodges MM, Ghatak S, Xu J, Singh S, Roy S, Sen CK, Seal S, Liechty KW. Use of Cerium Oxide Nanoparticles Conjugated with MicroRNA-146a to Correct the Diabetic Wound Healing Impairment. J Am Coll Surg. 2019 Jan;228(1):107-115. PubMed PMID: 30359833
  • Xu J, Zgheib C, Hodges MM, Caskey RC, Hu J, Liechty KW. Mesenchymal stem cells correct impaired diabetic wound healing by decreasing ECM proteolysis. Physiol Genomics. 2017 Oct 1;49(10):541-548. PubMed PMID: 28842435
  • Zgheib C, Hodges MM, Allukian MW, Xu J, Spiller KL, Gorman JH 3rd, Gorman RC, Liechty KW. Cardiac Progenitor Cell Recruitment Drives Fetal Cardiac Regeneration by Enhanced Angiogenesis. Ann Thorac Surg. 2017 Dec;104(6):1968-1975. PubMed PMID: 28821329
  • Zgheib C, Hodges MM, Hu J, Liechty KW, Xu J. Long non-coding RNA Lethe regulates hyperglycemia-induced reactive oxygen species production in macrophages. PLoS One. 2017;12(5):e0177453. PubMed PMID: 28494015
  • Zgheib C, Hodges M, Hu J, Beason DP, Soslowsky LJ, Liechty KW, Xu J. Mechanisms of mesenchymal stem cell correction of the impaired biomechanical properties of diabetic skin: the role of miR-29a. Wound Repair Regen. 2016 Jan 25. [Epub ahead of print] PubMed PMID: 26808714
  • Zgheib C, Hodges M, Hu J, Beason DP, Soslowsky LJ, Liechty KW, Xu J. Mechanisms of mesenchymal stem cell correction of the impaired biomechanical properties of diabetic skin: The role of miR-29a. Wound Repair Regen. 2016 Mar;24(2):237-46. PubMed PMID: 26808714
  • Zgheib C, Xu J, Mallette AC, Caskey RC, Zhang L, Hu J, Liechty KW. SCF increases in utero-labeled stem cells migration and improves wound healing. Wound Repair Regen. 2015 Jul-Aug;23(4):583-90. PubMed PMID: 26032674
  • Xu J, Zgheib C, Hu J, Wu W, Zhang L, Liechty KW. The role of microRNA-15b in the impaired angiogenesis in diabetic wounds. Wound Repair Regen. 2014 Sep-Oct;22(5):671-7. PubMed PMID: 25059098
  • Caskey RC, Zgheib C, Morris M, Allukian M, Dorsett-Martin W, Xu J, Wu W, Liechty KW. Dysregulation of collagen production in diabetes following recurrent skin injury: contribution to the development of a chronic wound. Wound Repair Regen. 2014 Jul-Aug;22(4):515-20. PubMed PMID: 24898050
  • Morris MW Jr, Allukian M 3rd, Herdrich BJ, Caskey RC, Zgheib C, Xu J, Dorsett-Martin W, Mitchell ME, Liechty KW. Modulation of the inflammatory response by increasing fetal wound size or interleukin-10 overexpression determines wound phenotype and scar formation. Wound Repair Regen. 2014 May-Jun;22(3):406-14. PubMed PMID: 24844340
  • Zgheib C, Allukian MW, Xu J, Morris MW Jr, Caskey RC, Herdrich BJ, Hu J, Gorman JH 3rd, Gorman RC, Liechty KW. Mammalian fetal cardiac regeneration after myocardial infarction is associated with differential gene expression compared with the adult. Ann Thorac Surg. 2014 May;97(5):1643-50. PubMed PMID: 24792251
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Professional Memberships

  • Wound Healing Society, Member
  • Wound Healing Society Award Committee, Member
  • American Heart Association, Member
  • The American Association for the Advancement of Science, Member
Personal Interests
My research has been focused primarily in the field of wound healing, the response to injury, and regenerative medicine, with an emphasis on elucidating the mechanisms involved in the regenerative response to injury in the fetus, the role of stem cells in tissue repair, and the correction of abnormal healing in the adult. The goal of this regenerative medicine approach is to restore normal tissue architecture and function and to prevent the complications of impaired healing or scar formation after injury. I completed my Ph.D. in molecular genetics in 2001 in the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. I has served as a postdoctoral fellow in Dr. Melissa Rogers’ lab in New Jersey Medical School, from 2002-05, and Dr. Jon Epstein’s lab in Upenn Medical School from 2005-09, Then I joined University Mississippi Medical Center, University of Colorado Anschutz campus as Assistant Professor in 2009 and 2014. I have a broad background in wound healing, with specific training and expertise in the role of non-coding RNA, including microRNAs, and long non-coding RNAs in diabetic wounds. My lab has pioneered the role of dysregulated microRNAs in the diabetic wound healing impairment, and the mechanisms of the correction of this wound healing impairment with stem cell and gene therapy. My team is developing novel treatment paradigms using stem cells, gene therapy strategies, and small molecule therapeutics to promote healing and tissue regeneration in multiple tissues by modulating the inflammatory response, angiogenesis, the composition of the extracellular matrix, and progenitor cell content.

Public Speaking
Yes

General Information

Internships:
  • University of Pennsylvania Program (2005)
  • UMDNJ-New Jersey Medical School Program (2002)
Languages: English
Department: Surgery-Peds Surgery
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