Nuria Morral, PhD
Associate Professor of Medical & Molecular Genetics
Associate Professor of Biochemistry & Molecular Biology
Executive Committee Member, Center for Diabetes and Metabolic Diseases
Enrichment Core Director, Center for Diabetes and Metabolic Diseases
- Phone
- (317) 278-9039
- Address
-
IB 130
MMGE
IN
Indianapolis, IN - PubMed:
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Bio
Research in the Morral lab focuses on understanding mechanisms by which nutrients influence gene expression, as well as elucidating how nutrient excess disrupts these normal processes, contributing to NAFLD and hepatic insulin resistance.
Education
1987 B. Sc. Biology, University of Barcelona, Spain
1993 PhD Molecular Genetics, University of Barcelona, Spain
1994-1998 Postdoctoral fellow, Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Academic Appointments
1999-2001 Instructor, Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY
2001-2003 Research Assistant Professor, Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY
2003-2009 Assistant Professor, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
2005-2009 Assistant Professor, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN
2009-present Associate Professor (tenured), Department of Medical and Molecular Genetics, and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN
2010 Visiting Professor, Swiss Federal Institute of Technology (ETH), Institute of Food, Nutrition and Health, Zurich, Switzerland
Honors and Awards
1994 Best Young Investigator Award on Human Genetics, Spanish Association of Human Genetics, Spain
1999-2003 Juvenile Diabetes Research Foundation International/Career Development Award
2009-2012 Member, American Society of Gene and Cell Therapy, Gene therapy of Genetic Diseases Committee
2009-2012 Standing member, American Diabetes Association Research Grant Review Committee
2011-2017 Standing Member, Gene and Drug Delivery Systems study section, NIH
2019-2025 Education Committee member, ASGCT
2020 ASGCT 24th Annual Meeting; Chair, Education Session: Gene Therapies for Liver Diseases
2022 ASGCT 25th Annual Meeting; Chair, Education Session: CRISPR/CAS9 Gene Editing - Concepts to In-Vivo Editing
Key Publications
Qian G, Morral N. Role of non-coding RNAs on liver metabolism and NAFLD pathogenesis. Human Molecular Genetics 31 (R1): R4-R21 (2022).
Saxena R, Nassiri M, Yin X-M, Morral N. Insights from a high-fat diet fed mouse model with a humanized liver. PLoS One 17(5):e0268260 (2022).
Morral N, Liu S, Conteh AM, Chu X, Wang Y, Dong XC, Liu Y, Linnemann A, Wan J. Aberrant gene expression induced by a high fat diet is linked to H3K9 acetylation in the promoter-proximal region. BBA-Gene Regulatory Mechanisms 1864:194691 (2021).
Jideonwo VN, Hou, Y., Ahn M, Surendran S, Morral N. Impact of silencing hepatic SREBP-1 on insulin signaling. PLoS ONE 13(5): e0196704 (2018).
Surendran S, Jideonwo VN, Merchun C, Ahn M, Murray J, Ryan J, Dunn K, Kota J, Morral N. Gene targets of mouse miR-709: regulation of distinct pools. Scientific Reports 6:18958 (2016).
Ruiz, R., Jideonwo, V., Ahn, M., Surendran, S., Tagliabracci, VS., Hou, Y., Gamble, A., Kerner, J., Irimia-Dominguez, JM., Puchowicz, MA., DePaoli-Roach, A., Hoppel, C., Roach, P., Morral, N. Sterol Regulatory Element Binding Protein-1 (SREBP-1) is required to regulate glycogen synthesis and gluconeogenic gene expression in mouse liver. Journal of Biological Chemistry 289:5510-5517 (2014).
Ruiz, R., Witting, S.R., Saxena, R., Morral, N. Robust hepatic gene silencing for functional studies using helper-dependent adenovirus vectors. Human Gene Therapy 20:87-94 (2009).
Morral, N., Edenberg, HJ., Witting, SR., Altomonte, J., Chu, T., Brown, M. Effects of glucose metabolism on regulation of genes of fatty acid synthesis and triglyceride secretion in the liver. Journal of Lipid Research 48:1499-1510 (2007).
Morral, N. Novel targets and therapeutic strategies for type 2 diabetes. Trends in Endocrinology and Metabolism 14:169-75 (2003).
Morral, N., O’Neal, W.K., Rice, R., Leland, M., Kaplan, J., Piedra, P.A., Zhou, H., Parks, R., Velji, R., Aguilar-Cordova, E., Wadsworth, S., Graham, F.L., Kochanek, S., Carey, K.D., Beaudet, A.L. Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons. Proceedings of the National Academy of Sciences USA (Track II) 96:12816-12821 (1999).
| Year | Degree | Institution |
|---|---|---|
| 1993 | PhD | University of Barcelona |
| 1987 | BSC | University of Barcelona |
Currently, 30% of the USA population has non-alcoholic fatty liver disease (NAFLD), a condition that is increasing in parallel with the global obesity epidemic and is a risk factor for type 2 diabetes and cardiovascular disease. Aberrant transcriptional control of gene expression constitutes a central aspect of the pathophysiology of metabolic diseases. Hundreds of genes become dysregulated and their gene products are abnormally expressed, leading to hepatic insulin resistance and cellular dysfunction. Research in the Morral lab is focused at understanding basic mechanisms through which nutrients and hormones influence gene expression. Understanding how these mechanisms become dysregulated and contribute to NAFLD will pave the way for future development of drugs to treat NAFLD and associated metabolic diseases.
An area of research focus is the identification of epigenetic mechanisms contributing to dysregulated gene expression in NAFLD. We have found that diet-induced obesity leads to mRNA changes that are strongly associated with alterations in histone H3 acetylation at lys9 (H3K9ac) in the promoter-proximal region of genes. This histone modification is used for recruitment of the Super Elongation Complex and activation of paused RNA pol II. Our goal is to understand how nutrients modulate RNA pol II pause-release, and assess whether this fundamental mechanism works aberrantly in NAFLD.
Another focus of the lab is Sterol Regulatory Element Binding Protein 1c (SREBP-1c), a transcription factor of the basic helix-loop-helix leucine zipper (bHLH-Zip) family that controls the expression of genes of the de novo lipogenesis synthesis pathway. SREBP-1 activity is increased in livers of individuals with obesity and animal models of obesity and T2D, contributing to enhance the flux of glucose towards acetyl-CoA production and de novo synthesis of fatty acids. Data generated from the Morral lab indicates that silencing SREBP-1 in the liver of an animal model of T2D is associated with significant changes in expression of carbohydrate metabolism genes, in addition to lipogenesis genes, and with a concomitant decrease in chromatin remodeling factors. These data suggest that the epigenetic machinery senses changes in energy availability, and responds accordingly to adjust gene expression.
To address these fundamental questions, we are using animal models of diabetes and gene transfer approaches with helper-dependent adenoviral vectors. Our lab is pioneer in using the helper-dependent adenoviral system to express short hairpin RNA (shRNA) in the liver.