Nuria Morral, PhD

Bio

Research in the lab focuses on understanding mechanisms by which nutrients influence gene expression, as well as elucidating how nutrient excess disrupts these normal processes, leading to 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

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

2017-2018 American Society of Gene and Cell Therapy, Oligonucleotide and RNAi Therapeutics Committee Chair

Key Publications

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).

Mansouri A, Pacheco-López G, Ramachandran D, Arnold M, Leitner C, Prip-Buus C, Langhans W, and Morral N. Enhancing hepatic mitochondrial fatty acid oxidation stimulates eating in food-deprived mice. The American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 308:R131-R137 (2015).

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).

Ahn, M., Witting, S.R., Ruiz, R., Saxena, R., Morral, N. Constitutive expression of shRNA in vivo triggers build up of mature hairpin molecules. Human Gene Therapy 22:1483-1497 (2011).

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).

Titles & Appointments

Associate Professor of Medical & Molecular Genetics
Associate Professor of Biochemistry & Molecular Biology
Associate Professor of Medical &amp
Molecular Genetics
Executive Committee Member, Indiana Diabetes Research Center
Enrichment Core Co-Director, Indiana Diabetes Research Center

Education

1993 PhD University of Barcelona

1987 BSC University of Barcelona
Research

Type 2 diabetes (T2D) is a complex multifactorial disease with a strong polygenic basis. However, environmental and lifestyle factors also play a significant role in disease development. My research is focused at understanding mechanisms through which nutrients and hormones influence gene expression, and elucidating basic mechanisms that lead to hepatic insulin resistance.

Sterol Regulatory Element Binding Protein 1c (SREBP-1c) is 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 our 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. Current research in the lab is focused at elucidating the contribution of epigenetics on the etiology of insulin resistance.

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.
Professional Organizations

American Diabetes Association

American Society of Gene Therapy

Spanish Association of Human Genetics

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