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
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IB 244B
MMGE
IN
Indianapolis, IN - PubMed:
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Bio
Dr. Morral's research is centered on elucidating the molecular basis of liver metabolism and how nutrient excess disrupts these normal processes, driving the development of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) and insulin resistance. To systematically dissect key regulatory nodes within the liver, her lab employs a diverse array of experimental models, including rodent models, primary human hepatocytes, advanced gene silencing techniques, and cutting-edge next-generation sequencing technologies.
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
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
Yadav AK, MacNeill JJ, Krylov A, Ashrafi N, Ashrafi Mimi R, Saxena R, Liu S, Graham SF, Wan J, Morral N. Sex and age-associated factors drive the pathophysiology of MASLD. Hepatology Communications 8:e0523 (2024).
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).
| Year | Degree | Institution |
|---|---|---|
| 1993 | PhD | University of Barcelona |
| 1987 | BSC | University of Barcelona |
Currently, 30% of adult Americans are affected by Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), a condition that is increasing in parallel with the global obesity epidemic. MASLD is a significant 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. 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 MASLD will pave the way for future development of drugs to treat MASLD and associated metabolic diseases.
Pioneering Adenoviral Vector Technology for Hepatic Gene Silencing
Early foundational research significantly contributed to the field of gene therapy, particularly in the development and optimization of adenoviral vectors. A landmark achievement was the demonstration that genomic DNA transfer with high-capacity helper-dependent adenoviral vectors resulted in markedly improved in vivo gene expression and decreased toxicity. Building on this expertise in gene delivery, Dr. Morral’s research transitioned to developing robust hepatic gene silencing methodologies using helper-dependent adenoviral vectors for functional studies, with a focus on metabolic diseases and type 2 diabetes.
SREBP-1: Key Regulator of Liver Metabolic Balance
Early work identified the crucial interplay between hepatic glucose metabolism and the regulation of genes governing fatty acid synthesis and triglyceride secretion, providing foundational insights into the liver's metabolic flexibility. Utilizing helper-dependent adenovirus vector technology to achieve Sterol Regulatory Element Binding Protein-1 (SREBP-1) knockdown in db/db mice, Dr. Morral's lab made the novel and significant discovery that SREBP-1 plays an essential role in orchestrating both glycogen synthesis and gluconeogenic gene expression, extending beyond its known involvement in lipogenesis. Complementary research highlighted the crucial importance of glycogen, showing that its deficiency induces hepatic insulin resistance and steatosis, thus establishing a critical link between glycogen storage and proper insulin and lipid metabolism. This was further substantiated by studies dissecting the impact of SREBP-1 silencing on insulin signaling pathways, revealing the complex interplay between lipid and glucose metabolism in the context of insulin sensitivity. Together, these findings emphasize the delicate balance between lipid and carbohydrate metabolism in the liver, where SREBP-1 influences both glycogen production and glucose output, and sufficient glycogen storage is essential for maintaining insulin sensitivity and preventing lipid accumulation.
The role of epigenetic regulation in MASLD pathophysiology
More recently, Dr. Morral's research has pioneered the exploration of epigenetic modifications in the context of liver disease. Using ChIP-seq, ATAC-seq, and RNA-seq they have demonstrated that aberrant gene expression driven by a high-fat diet is tightly linked to specific histone acetylation patterns (H3K9ac) in the promoter regions of affected genes, revealing a key mechanism by which environmental cues can reshape the hepatic transcriptome. In a significant contribution to the understanding of MASLD heterogeneity, the most recent work has directly addressed the critical influence of sex and age on disease pathophysiology, providing crucial insights into the differential susceptibility and progression of MASLD across these biological variables. This research extends to the fundamental mechanisms underlying sex-specific liver functions, implicating the histone modification H3K9me3 as well as DNA methylation.
Collectively, Dr. Morral's research focuses on understanding liver metabolism and the pathogenesis of MASLD, spanning from fundamental metabolic pathways to the intricate layers of epigenetic control, with a clear and growing focus on the critical roles of sex and age in shaping disease. These findings hold substantial promise for the development of more targeted and personalized therapeutic interventions for this prevalent liver disease.