Department of Physiology and Cell Biiology

 

 

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Seungil Ro, Ph. D.

Assistant Professor


My research interest is studying the roles of microRNAs (miRNAs) that control gut neuromuscular (motility) disorders. The gut is a vital organ for human survival: it is where food is digested, where nutrients are absorbed into the bloodstream, and where undigested waste moves through and leaves the body. This digestive process is achieved by the synchronized movement (motility) of gastrointestinal (GI) muscle, which mixes food and propels the digested content through the GI tract. Motility of GI muscle is controlled by three key cells: enteric nervous system (ENS), interstitial cells of Cajal (ICC), and smooth muscle cells (SMCs). ENS and ICC generate complex rhythmic motor behavior and spontaneous electrical slow waves, respectively, both of which control SMCs, the final effectors for muscle contraction and muscle relaxation. Developmental abnormalities and pathophysiological damage of these cells are directly linked to GI neuromuscular diseases such as Hirshsprung’s disease, diabetic gastroenteropathy (DGEP), gastrointestinal stromal tumor (GIST), and chronic intestinal pseudo-obstruction (CIPO). All these motility diseases are thought to be developed from the remodeling of the smooth muscle in the GI tract, leading to abnormal growth (hypertrophy or tumor) or death (myopathy) of the cells. miRNAs are a new class of small RNAs that are known to be powerful regulators of gene expression during animal development. Our previous studies discovered that miRNAs regulate SMC growth and differentiation in the GI tract, which are required for the animals’ survival. However, the cellular and molecular mechanisms underlying remodeling of the GI smooth muscle by miRNAs in motility disorders are largely unknown. We have currently generated several animal models with GI motility disorders (myopathy, hypertrophy, and diabetic gastroenteropathy) using: conventional cell-specific gene deletion (Dicer, Srf, and Dnmt1), inducible cell-specific gene deletion (Dicer, Srf, and Dnmt1), a congenital mutation (Edn3), a partial obstruction surgery on the small intestine, a conventional gene deletion (Lep), and a spontaneous gene mutation (TALLYHO/JungJ). In the animal models, SMCs or ICC are labeled with green fluorescent protein (GFP) (Fig. 1). We have developed cytometric techniques to isolate SMCs or ICC from the GFP mice using GFP, as well as non-GFP mice using cell specific surface markers. The GFP animal models are a powerful tool for studying the genetic, cellular, and functional changes in the motility disorders. Using these animal models, we seek to uncover novel mechanisms involving miRNAs that lead to the abnormal growth or loss of SMCs and ICC during the development of motility disorders. Identifying such mechanisms will aid not only in the development of a diagnostic tool for various neuromuscular diseases, but also of a therapeutic target that has the potential to reverse the genetic changes that are responsible for these pathological conditions, and thus possibly reverse some of the unwanted pathological changes that occur in these diseases.

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Fig. 1. GFP-labeled SMCs (A) and ICC (B) in the muscle layers of small intestine.

Smooth Muscle and Non-Coding RNAs Lab

 Location: Anderson Room 107 and 109

 Phone: 775-682-8838 (Room 107) and 775-784-1647 (Room 109)

Lab Members
Dr. Chanjae Park Chanjae Park PhD
Research Assistant Professor
  Dr. Paul Park Paul Park MD PhD
Post-Doctoral Fellow
Robyn Berent

Robyn Berent
CMPP PhD Student

  Nicholas Collins Nicholas Collins
IRUP Student
James Parkinson James Parkinson
IRUP Student
  Hannah Syn Hannah Syn
Biochemistry Undergraduate
Robby Fuchs Robby Fuchs
Biology Undergraduate
  Albert Chin Albert Chin
Biology Undergraduate
Jessica King Jessica King
Biochemistry Undergraduate
  Jessica King

Timothy Yu
Spanish Undergraduate

Jessica King Anton Abiog
Biology Undergraduate
  Jessica King Crystal Viss
Biology Undergraduate
         

Collaborators:

Kenton M. Sanders , Ph. D. (University of Nevada, School of Medicine)
Pankaj J. Pasricha, M.D. (Johns Hopkins, Medicine)
Sean M. Ward, Ph. D. (Unviversity of Nevada, School of Medicine)
Joseph M. Miano, Ph. D. (University of Rochester)
Wei Yan, M.D., Ph.D. (Unviversity of Nevada, School of Medicine)
Terence Smith, Ph.D. (Unviversity of Nevada, School of Medicine)
Laren S. Becker, M.D. (Stanford University, School of Medicine)
Brian Perrino, Ph.D. (Unviversity of Nevada, School of Medicine)
Kazuhide Horiguchi, Ph.D. (Unviversity of Fuki, Medical Sciences, Japan)
Minsheng Zhu, Ph.D. (Nanjing University, Model Animal Research Center, China)
Brian P. Rubin, Ph.D. (Cleveland Clinic, Taussig Cancer Center and Lerner Research Institute)
Dieter Saur, M.D. (Technische Universität München, Internal Medicine 2, Germany)
Doug Redelman, Ph. D. (Unviversity of Nevada, School of Medicine)
Grant Hennig, Ph. D. (Unviversity of Nevada, School of Medicine)
Karen Schlauch, Ph. D. (Unviversity of Nevada)
Michael I. Kotlikoff, VMD, Ph. D. (Cornell University)
Jong Kun Park, Ph. D. (Wonkwang University, Korea)
Stefan Offermanns, M.D. (University of Heidelberg, Germany)
Laurie Jackson-Grusby, Ph. D. (Children's Hospital Boston / Harvard Medical School)
Pin Wang, Ph. D. (USC Viterbi School of Engineering)
Tae-wan Kim, Ph. D. (Kyungpook National University, Korea)

Search For Dr. Ro's Publications In PubMed


Selected Publications

Ro S, Ma HY, Park C, Ortogero N, Song R, Hennig GW, Zheng H, Lin YM, Moro L, Hsieh JT, Yan W. The mitochondrial genome encodes abundant small noncoding RNAs. Cell Research, doi: 23(6) : 759-74, 2013

Sanders KM, Koh SD, Ro S, Ward SM. Regulation of gastrointestinal motility – insights from smooth muscle biology. Nature Reviews Gastroenterology & Hepatology, 9(11):633-45, 2012

Park C, Yan W, Ward SM, Hwang S, Wu Q, Hatton WJ, Park J, Sanders KM, Ro S. MicroRNAs dynamically remodel gastrointestinal smooth muscle cells. PLoS ONE, 6(4): e18628, 2011

Park C, Hennig GW, Sanders KM, Cho JH, Hatton W, Redelman D, Park J, Ward SM, Miano JM, Yan W, Ro S. Serum Response Factor-dependent microRNAs regulate gastrointestinal smooth muscle cell phenotypes. Gastroenterology, 141(1): 164-175

Ro S, Yan W. Small RNA cloning. Methods in Molecular Biology, 629:273-85, 2010

Ro S, Yan W. Detection and quantitative analysis of small RNAs by PCR. Methods in Molecular Biology, 629:295-305, 2010

Ro S, Park C, Jin J, Zheng H, Blair P, Redelman D, Ward SM, Yan W, Sanders KM. A model to study the phenotypic changes of interstitial cells of Cajal (ICC) in gastrointestinal diseases. Gastroenterology, 138(3):1068-1078, 2009

Song R*, Ro S*, Michaels J, Park C, McCarrey JR, Yan W. Many X-linked microRNAs escape meiotic sex chromosome inactivation. Nature Genetics, 41(4):488-93, 2009

Ro S, Song R, Park C, Zheng H, Sanders KM, Yan W. Cloning and Expression Profiling of Small RNAs Expressed in the Mouse Ovary. RNA, 13(12):2366-80, 2007. (Supplementary Data)

Ro S, Park C, Sanders KM, McCarrey JR, Yan W. Cloning and Expression Profiling of Testis-Expressed miRNAs. Developmental Biology, 311(2):592-602, 2007

Ro S, Park C, Young D, Sanders KM, Yan W. Tissue-dependent paired expression of miRNAs. Nucleic Acids Research, 35(17):5944-53, 2007

Ro S*, Park C, Song R, Nguyen D, Jin J, Sanders KM, McCarrey JR, Yan W. Cloning and Expression Profiling of Testis-Expressed piRNA-like RNAs. RNA, 13(10):1693-702, 2007. (Supplementary Data)

Ro S, Park C, Jin J, Sanders KM, Yan W. A PCR-based Method for Detection and Quantification of Small RNAs. Biochemical and Biophysical Research Communications, 351(3):756-63, 2006

Ro S, Kang SH, Farrelly AM, Ordog T, Partain R, Fleming N, Sanders KM, Kenyon JL, Keef KD. Template switching within exons 3 and 4 of KV11.1 (HERG) gives rise to a 5' truncated cDNA. Biochemical and Biophysical Research Communications, 345(4):1342-49, 2006

Ro S, Hwang SJ, Muto M, Jewett WK, Spencer NJ. Anatomical modifications in the enteric nervous system of piebald mice and the physiological consequences to colonic motor activity. American Journal of Physiology, 290(4):G710-18, 2006

Ro S, Hwang SJ, Ordog T, Sanders KM. Adenovirus-based short hairpin RNA vectors containing an eGFP marker and mouse U6, human H1 or human U6 promoter, , BioTechniques, 38(4):625-27, 2005

Ro S, Hatton WJ, Koh SD, Horowitz B.  Molecular properties of small conductance Ca2+ activated K+ channels expressed in murine colonic smooth muscle. American Journal of Physiology 281(4):G964-73, 2001

*Equally contributed

Patent:

Ro S and Ewing NN. Promoter of the tomato expansin gene LeExp-1. U.S. Patent number 6,340,748 (http://patft.uspto.gov/netahtml/PTO/srchnum.htm)

Technology Transfer:

Ro S, Yan W and Sanders KM. Transgenic line B6.129S7-Kit (tm1Rosan/J) transferred to The Jackson Laboratory. STOCK#15813, 2011

Microarray Data Deposit in GEO:

Park C and Ro S. MicroRNAs dynamically remodel gastric smooth muscle cells. GSE21738, 2010