Summary
- 2019-present Director, Cellular and Molecular Pharmacology and Physiology Graduate Program
- 2015-present Associate Professor, Physiology & Cell biology
- 2007-2015 Assistant Professor, Physiology & Cell biology
- 2004-2007 Research Assistant Professor, Physiology & Cell biology
- 2003-2004 Post-Doctoral Fellow, Physiology & Cell biology, UNR
Research interests
My research interests are focused on elucidating the roles of microRNAs (miRNAs) that control diabetes, obesity, fatty liver disease, gut neuromuscular disorders, and COVID-19. We have identified anti-diabetic miRNAs (Singh R and Ha S et al, Gastroenterology 2021; PCT Int’l Patent WO/2020/219872), which have a prolonged effect on diabetes, obesity, fatty liver disease, and gut dysmotility in animal models. The miRNAs also have been shown to prevent the onset of diabetes and obesity in animal models. Our research suggests miRNAs prevent the onset of diabetes in young and healthy individuals, but aging, poor diet and/or lack of exercise reduce the expression of the anti-diabetic miRNAs, triggering the development of these diseases. Restoring the miRNAs remarkably reverses diabetes by recovering the function of beta cells, adipocytes, and skeletal muscle (insulin production and sensitivity) in animal models. In addition, the miRNAs dramatically reverse obesity, fatty liver disease (steatosis and fibrosis), and dysmotility in the GI tract.
Furthermore, we identified anti-coronavirus miRNAs that are depleted in COVID-19 patients. The miRNAs target all members of the human α and β coronavirus family including SARS, MERS, and SARS-CoV-2. SARS-CoV-2 have multiple target sites on key viral proteins including RNA-dependent RNA Polymerase and the Spike protein. All the target sites are conserved in the seven SARS-CoV-2 variants including delta and omicron. The miRNAs target the RNA genome and subgenomic RNAs to reduce replication and protein synthesis. In addition, the miRNAs reduce expression of proinflammatory cytokines IL-6 and TNFα as well as IL-6R by targeting their transcription factors ATF6 and E2F3.
When patients with diabetes and/or obesity are infected with SARS-CoV-2, the severity and fatality of COVID-19 symptoms is drastically increased. Using anti-diabetic miRNAs, anti-coronavirus miRNAs, and mouse models with diabetes and/or COVID-19, we are performing preclinical studies to develop therapeutic approaches to treat these diseases.
We launched a biotech startup company “RosVivo Therapeutics Inc” in March, 2021. RosVivo has received Series A funding and is working with leading global biopharma companies specializing in diabetes care to develop therapeutic miRNAs that can prevent and rescue these diseases.
Selected publications
- Breland A*, Ha S*, Jorgensen BG*, Jin B, Gardner TA, Sanders KM, Ro S. Smooth Muscle Transcriptome Browser: offering genome-wide references of transcripts expressed in intestinal tissues and cells. Scientific Reports, 23;9(1):387, 2019 *Equally contributed
- Jorgensen BG, Ro S. Role of DNA methylation in the development and differentiation of intestinal epithelial cells and smooth muscle cells. J Neurogastroenterol Motil, 25(3):377-386, 2019
- Ha S, Wei L, Jorgensen BG, Lee MY, Park PJ, Poudrier SM, Ro S. A mouse model of intestinal partial obstruction. Journal of Visualized Experiments, 133, 2018
- Jorgensen BG*, Berent RM*, Ha S*, Horiguchi K, Sasse KC, Becker LS, Ro S. DNA methylation, through DNMT1, has an essential role in the development of gastrointestinal smooth muscle cells and disease. *Equally contributed. Cell Death Dis, 9: 474, 2018
- Lee MY, Park C, Ha S, Park PJ, Berent RM, Jorgensen BG, Corrigan R, Grainger N, Blair JP, Slivano OJ, Miano JM, Ward SM, Smith TK, Sanders KM, Ro S. Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels. PLoS ONE, 12(2):e0171262, 2017
- Lee MY*, Ha S*, Park C*, Park PJ, Fuchs R, Wei L, Jorgensen BG, Redelman D, Ward SM, Sanders KM, Ro S. Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures. PLoS ONE, 12(4):e0176031, 2017 *Equally contributed
- Ha S, Lee MY, Kurahashi M, Wei L, Jorgensen BG, Park C, Park PJ, Redelman D, Sasse KC, Becker LS, Sanders KM, Ro S. Transcriptome analysis of PDGFRα+ cells identify T-type Ca2+ channel CACNA1G as a new pathological marker for PDGFRα+ cell hyperplasia. PLoS ONE, 12(8):e0182265, 2017
- Ro S. Multi-Phenotypic Role of Serum Response Factor in the Gastrointestinal System. J Neurogastroenterol Motil, 22(2):193-200, 2016
- Park C, Lee MY, Slivano OJ, Park PJ, Ha S, Berent RM, Fuchs R, Collins NC, Yu T, Syn H, Park JK, Horiguchi K, Miano JM, Sanders KM, Ro S. Loss of serum response factor induces microRNA-mediated apoptosis in intestinal smooth muscle cells. Cell Death Dis, 6:e2011. doi: 10.1038/cddis.2015.353, 2015
- Park C*, Lee MY*, Park PJ, Ha S, Berent RM, Fuchs R, Miano JM, Becker LS, Sanders KM, Ro S. SRF is essential for prenatal gastrointestinal smooth muscle development and maintenance of differentiated phenotype. J Neurogastroenterol Motil, 21(4): 589-602, 2015 *Equally contributed
- Lee M, Park C, Berent R, Park PJ, Fuchs R, Syn H, Chin A, Townsend J, Benson CC, Redelman D, Shen T, Park J, Miano JM, Sanders KM, Ro S. Smooth muscle cell genome browser: enabling the identification of novel serum response factor target genes. PLoS ONE, In print 2015
- 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, 2011
- 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
- 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
- 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 expansion gene LeExp-1. U.S. Patent number 6,340,748, Issued January 22, 2002
- Ro S. MiR-10 mimic and targets thereof for use in the treatment of diabetes and gastrointestinal motility disorders. U.S. Patent, provisional, 2019
Technology Transfer
- Ro S, Yan W and Sanders KM. Transgenic line B6.129S7- Kittm1Rosan/J transferred to The Jackson Laboratory. STOCK#15813, 2011
- Smooth Muscle Genome/Transcriptome/Methylome Databases
- The databases are available.
- UCSC Smooth Muscle Genome Browser: The UCSC Smooth Muscle Genome Browser is an interactive browser that was built with custom tracks of transcriptomes from intestinal smooth muscle, mucosa, as well as sorted cells (SMC, ICC, and PDGFRα+ cells) including CArGome [serum response factor (SRF) binding sites] reference sites. This browser provides a comprehensive reference for all transcriptional variants expressed in the cell populations, GI tissues, and genome-wide SRF binding sites. The browser can also interact with the genome bioinformatics (e.g. ENCODE) data publically available in the UCSC Genome Browser.
- Smooth Muscle Transcriptome Browser: The Transcriptome Browser offers genome-wide genetic references that bring new insight into genetic structures, expression profiles, and isoforms of each individual gene expressed in the key cell populations for functional studies.
- UCSC Smooth Muscle Methylome Browser: The UCSC Smooth Muscle Methylome Browser is an interactive browser that was built with custom tracks representing the methylome and transcriptome of Dnmt1-WT and Dnmt1-KO murine jejunal smooth muscle. This browser provides a comprehensive reference for genomic DNA methylation status at CpG sites in Dnmt1-WT and Dnmt1-KO. The browser can also interact with the genome bioinformatics (e.g. ENCODE) data publically available in the UCSC Genome Browser.
Principal lab members
- Se Eun Ha PhD, Research Assistant Professor
- Rajan Singh, PhD, Post-Doctoral Fellow
- Lai (Lisa) Wei PhD, Post-Doctoral Fellow
- Brian Jorgensen, PhD, Post-Doctoral Fellow
- Byungchang Jin, Graduate Student (CMB)
- Hannah Zogg, Graduate Student (CMB)
- Allison Bartlett, Graduate Student (CMPP)
- Ga-in Beak, Graduate Student (Wonkang University, South Korea)
- Sandra Poudrier, Lab Manager (SRA II)
Other lab members
Medical students volunteers (2019)
- Brooke Clemmensen
- Robert Gullickson
- Denise Julian
- Charles Ronkon
Undergraduate thesis students and volunteers (2019)
- Mirabel Dafinone, Biochemistry and Molecular Biology (2016- present)
- Yixin Huang, Biochemistry and Molecular Biology (2019-present)
- Evan Lipschultz, Biochemistry and Molecular Biology
- Kaitlyn Solomon, Biochemistry and Molecular Biology (2017-2019)
- Marielle Tedlos Chemistry with Premed emphasis (2019-present)
Teaching
Medical students
Block 1: Foundations and Principles of Medical Sciences, CELL BIOL: Protein Synthesis, Modifications & Targeting, Molecular Biology and Forensics, Cell Renewal, Cell Death & Apoptosis
Graduate students
- BCH 705: Translation, Using the Genetic Code, Molecular Genetics, Regulatory RNAs, and Epigenetic Effects
- CMPP794 Journal Club: Gastrointestinal motility disorders and related metabolic diseases
- PCB 711: Genetic methods of physiological experimentation
Undergraduate students
- BIO298, 491, 492 Independent Study
- BCH 407/408 Senior Thesis
Press
- Channel 2 News, April 19, 2018: $2M Granted to UNR School of Medicine Researchers for Diabetes Breakthrough Discovery
- Channel 4 News, April 17, 2018: UNR doctor discovers molecule that could be the key to curing type 2 diabetes
- KOHAM780 News, April 18, 2018: UNR Associate Professor Makes Breakthrough in Diabetes Research
- NEVADAToday April 17, 2018: $2 million awarded for path to new diabetes treatment
- UNR SOM News & Events, April 17, 2018: University of Nevada, Reno School of Medicine researcher makes discovery, awarded $2M for path to new diabetes treatment
- Generation Boomer, June 6, 2018: UNR School of Medicine Researcher Awarded $2M for New Diabetes Treatment
- PR Newswire / US Newswire, April 17, 2018 : Research discovery awarded $2 million for path to new diabetes treatment
- MARKETS INSIDER, April 17, 2018: Research discovery awarded $2 million for path to new diabetes treatment
- ForImmediateRelease.net, April 17, 2018: Research discovery awarded $2 million for path to new diabetes treatment
Education
- Ph.D., Cell & Molecular Biology, University of Nevada, Reno, 2002
- M.S., Biological Sciences, California State University, Sacramento, 1999
- M.S., Molecular Biology, Wonkwang University, Korea, 1994
- B.S., Molecular Biology, Wonkwang University, Korea, 1992