|Administrative Title: Vice Chair
The Joseph and Corinne Schwartz Professorship in Surgery
10 North Greene, VAMC
(410) 605-7000 ×5678
Dr. Jian-Ying Wang received his medical degree from Sun Yat-Sen University School of Medicine, China, in 1978 and Ph.D degree from Peking (Beijing) University School of Medicine in 1986. He then completed postdoctoral training at Kyoto Pharmaceutical University, Japan, and University of Texas School of Medicine at Houston.
In 1994, Dr. Wang joined the faculty of University of Maryland School of Medicine as an assistant professor. He was subsequently promoted to associate professor with tenure in 1998 and professor in 2002. Dr. Wang has been appointed as an associate chair for basic research of the Department of Surgery from 2005. Dr. Wang is also an investigator of Medical Research Service, US Department of Veterans Affairs, and he has been selected as an honor position as Senior Research Career Scientist from 2011.
Dr. Wang has published 131 original research articles, 19 review articles and book chapters, and 3 reference books on gut physiology and polyamine topics. Dr. Wang's research program has been continuously funded by multiple NIH grants and VA Merit-Review grants for more than twenty years. His service to the scientific community is also exceptional, as Dr. Wang serves as a member of multiple NIH study sections and VA-MERIT Review study sections, and is also on the editorial board for several scientific journals.
Dr. Wang's research focuses on understanding of how gut mucosa functions to repair itself after injury and how gut epithelial integrity is maintained under biological and critical pathological conditions, with specifically focusing on the importance of cellular polyamines in these processes. The natural polyamines (spermidine and spermine and their precursor putrescine) are organic cations found in all eukaryotic cells and are implicated in many aspects of cellular physiology. Studies in Dr. Wang's laboratory are to define the exact roles and mechanisms of polyamines and polyamine-regulated genes in the regulation of gut epithelial cell proliferation, apoptosis, migration, and cell-cell interaction.
He first reported that polyamines stimulate repair of damaged mucosa and are crucial for maintaining the gut epithelial integrity. His group further found that polyamines up-regulate expression of growth-promoting genes by increasing gene transcription but down-regulate growth-inhibiting genes through destabilization of mRNAs. His group has further elucidated critical mechanism underlying posttranscriptional gene regulation by polyamines, finding that polyamines regulate the stability and translation of mRNAs via RNA-binding proteins and microRNAs. Importantly, Dr. Wang's research projects are directly relevant to patients with trauma, hemorrhage, and massive surgical operations. The ongoing studies in Dr. Wang's group is to further define the link between the posttranscriptional gene regulation and mucosal injury/repair, inflammation, leaky gut, and sepsis.
In addition, Dr. Wang has successfully mentored young scientists and junior faculty. During the past five years, six trainees under Dr. Wang's mentorship received NIH grants, VA Career development Awards, and VA Merit-Review Awards. Dr. Wang's research program has added depth and a higher level of sophistication to our biomedical research community in general.
Lab Techniques and Equipment:
The Wang laboratory uses physiology, cell biology, biochemistry, molecular biology, and transgenic/knockout mouse models to study gut mucosal growth, injury/repair, and barrier function. This includes molecular cloning and expression of regulatory proteins, cellular transfection with cDNAs or microRNAs and infection with adenovirus, nuclear run-on transcription assays and gel shift assays, ribonucleoprotein and biotin pulldown assays, polysome profile analysis, promoter deletion and point mutations, and fluorescence measurement of intracellular Ca2+ concentration, and measurements of paracellular permeability and barrier functions.
- Jaladanki N. Rao, Ph.D - Assistant Professor
- Tongtong Zou, MD and Ph.D - Instructor
- Lan Liu, MD - Research Associate
- Lan Xiao, MD - Instructor
- Navneeta Rathor, MD - Postdoctoral Research Fellow
- Ran Zhang, MD and Ph.D - Postdoctoral research fellow
- Miao Ouyang, MD - Postdoctoral Research Fellow
- Shan Cao, MD and Ph.D - Postdoctoral Research Fellow
- Pornima Phatak, Ph.D - Postdoctoral Research Fellow
- Natasha Z. Hansraj, MD - Surgical Resident
- Daniel Mansour, MD - Surgical Resident
- Li L, Liu L, Rao JN, Esmaili A, Strauch ED, Bass BL, and Wang JY. JunD stabilization results in inhibition of normal intestinal epithelial cell growth through p21 after polyamine depletion. Gastroenterology 123:764-779, 2002.
- Zhang HF, Rao JN, Guo X, Liu L, Zou T, Turner DJ, and Wang JY. Akt kinase activation blocks apoptosis in intestinal epithelial cells by inhibiting caspase-3 after polyamine depletion. J Biol Chem 279:22539-22547, 2004.
- Zou T, Mazan-Mamczarz K, Rao JN, Liu L, Marasa BS, Zhang AH, Xiao L, Pullmann R, Gorospe M, and Wang JY. Polyamine depletion increases cytoplasmic levels of RNA-binding protein HuR leading to stabilization of nucleophosmin and p53 mRNAs. J Biol Chem 281:19387-19394, 2006.
- Xiao L, Rao JN, Zou T, Liu L, Marasa BS, Chen J, Turner DJ, Zhou H, Gorospe M, and Wang JY. Polyamines regulate the stability of activating transcription factor-2 mRNA through RNA-binding protein HuR in intestinal epithelial cells. Mol Biol Cell 18:4579-4590, 2007.
- Chen J, Rao JN, Zou T, Lan L, Xiao L, Bellavance E, Gorospe M, and Wang JY. JunD represses transcription and translation of the tight junction protein zona occludens-1 modulating intestinal epithelial barrier function. Mol Biol Cell 19:3701-3712, 2008.
- Zhang X, Zou T, Rao JN, Liu L, Xaio L, Wang PY, Cui YH, Gorospe M, and Wang JY. Stabilization of XIAP mRNA through the RNA-binding protein HuR regulated by cellular polyamines. Nucleic Acids Res 37:7623-7637, 2009.
- Liu L, Rao NJ, Zou T, Lan X, Wang PY, Turner DJ, Gorospe M, and Wang JY. Polyamines regulate c-Myc translation through Chk2-dependent HuR phosphorylation. Mol Biol Cell20:4885-4898, 2009.
- Zou T, Rao JN, Liu L, Xiao L, Yu TX, Jiang P, Gorospe M, and Wang JY. Polyamines regulate the stability of JunD mRNA by modulating the competitive binding to its 3’ untranslated region to HuR and AUF1. Mol Cell Biol 30: 5021-5032, 2010.
- Xiao L, Cui YH, Rao JN, Zou T, lIU l, Yu TX, Smith A, Turner DJ, Gorospe M, and Wang JY. Regulation of cycylin-dependent kinase 4 translation through CUGBP1 and miR-222 by polyamines. Mol Biol Cell 22: 3055-3069, 2011.
- Cui YH, Xiao L, Rao JN, Zou T, Liu L, Chen Y, Turner DJ, Gorospe M, and Wang JY. miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies. Mol Biol Cell 23: 151-162, 2012.
- Chung HK, Rao JN, Zou T, Liu L, Xiao L, Gu H, Turner DJ, Yang P, and Wang JY. Jnk2 deletion disrupts intestinal mucosal homeostasis and maturation by differentially modulating RNA-binding proteins HuR and CUGBP1. Am J Physiol C1167-C1175, 2014.
- Liu L, Christodoulou-Vafeiadou E, Rao JN, Zou T, Xiao L, Chung HK, Yang H, Gorospe M, Kontoyiannis D, Wang JY. RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway. Mol Biol Cell 25:3308-3318, 2014
- Rathor N, Chung HK, Mahavadi S, Wang JY, Turner DJ, and Rao JN. Caveolin-1 enhances rapid mucosal restitution by activating TRPC1-mediated Ca2+ signaling. Physiol Report published online: 2 (11). pii: e12193. doi: 10.14814/phy2.12193, 2014.
- Ouyang M, Su W, Xiao L, Rao JN, Jiang L, Li Y, Turner DJ, Gorospe M, and Wang JY. Modulation by miR-29b of intestinal epithelium homeostasis through the repression of menin translation. Biochem J 465:315-323, 2015.
- Gu H, Yu J, Dong D, Zhou Q, Wang JY, and Yang P. The miR-322-TRAF3 circuit mediates the pro-apoptotic effect of high glucose on neural stem cells. Toxicol Sci 144:186-196, 2015.
- Liu L, Rao JN, Zou T, Xiao L, Chung HK, Wu J, Gorospe M, and Wang JY. Competition between RNA-binding proteins CELF1 and HuR modulates MYC translation and intestinal epithelium renewal. Mol Biol Cell 26:1797-1810, 2015.
- Zou T, Rao JN, Liu L, Xiao L, Chung HK, Li YW, Gorospe M, and Wang JY. JUND enhances miR-29b levels transcriptionally and post-transcriptionally to inhibit cell proliferation. Am J Physiol Cell 308:C813-C824, 2015.
- Donahue J, Phatak P, Byrnes K, Mansour D, Liu L, Cal S, Li R, Rao JN, Turner DJ, and Wang JY. Overexpression of miR-214-3p in esophageal squamous cancer cells enhances sensitivity to cisplatin by targeting surviving directly and indirectly through CUG-BP1. Oncogene, accepted for publication on June 5, 2015.
- Chung HK, Chen Y, Rao JN, Liu L, Xiao L, Turner DJ, Yang P, Gorospe M, and Wang JY. Transgenic expression of miR-222 disrupts growth and protection of small intestinal mucosa by targeting Wnt receptor Frizzled-7. Mol Med (In Review), 2015.
- Xiao L, RaoJN, Cao S, Liu L, Chung HK, Zhang Y, Liu Y, Gorospe M, and Wang JY. Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins. EMBO Report (In Revision), 2015.
II. Reviews, Book Chapters, and Others:
- Yang H, Rao JN, and Wang JY. Posttranscriptional regulation of intestinal epithelial tight junction barrier by RNA-binding proteins and microRNAs. Tissue Barrier 2:e28320(1-8), 2014.
- Xiao L and Wang JY. RNA-binding proteins and microRNAs in gastrointestinal epithelial homeostasis and diseases. Current Opinion in Pharmacology 19:46-53, 2014.
- Takeuchi K and Wang JY. Editorial overview: Gastrointestinal: Gastrointestinal research –mucosal injury, protection, and repair at organ, cellular, and molecular levels. Current Opinion in Pharmacology 19:1-2, 2014.