Luis Villacorta, PhD, FAHA 

Education

POSTGRADUATE:
University of Michigan
Fellowship: Cardiovascular Medicine

GRADUATE:
University of Bern, Switzerland
Degree: Doctor of Philosophy in Biochemistry

UNDERGRADUATE:
Autonoma University of Madrid, Spain
Degree: Bachelor of Science in Biochemistry and Molecular Biology

Research Interests

Dr. Villacorta’s research focuses on the interplay between inflammatory responses and energy metabolism, with special emphasis on vascular, liver and adipose tissues. In particular, Dr. Villacorta studies the role of bioactive nitrated fatty acids in the pathophysiology of obesity, diabetes and aligned-cardiovascular and -liver diseases geared towards the development of novel therapeutic approaches. Nitrated fatty acids have emerged as potent anti-inflammatory and anti-fibrotic signaling mediators. These lipids are generated during inflammation and digestion through non-enzymatic reactions of unsaturated fatty acids with nitrogen dioxide, yielding an array of electrophilic nitro-fatty acids with unique biochemical and signaling properties. Furthermore, their safety and pharmacokinetics have been clinically examined in phase I trials and its therapeutic potential currently evaluated in phase II clinical trials.

1. Nitro-fatty acids-based therapeutics against fatty liver diseases. Current research interest include developing nitro-fatty acids as potential therapeutic strategy against diseases involving imbalanced lipid metabolism, inflammation and fibrosis, including non-alcoholic fatty liver disease (NAFLD). Our previous experience with nitro-fatty acids has taught us that these bioactive lipids exert potent metabolic benefits as well as anti-inflammatory and anti-fibrotic properties. We work at biochemical, cellular and physiological levels, applying relevant approaches, including genetic (CRISPR/Cas9 tools), and “-omics” (lipidomics, metabolomics) for identification and validation of novel molecular targets of nitrated fatty acids with therapeutic potential.
   
   
2. Identification of molecular determinants of tissue inflammation and fibrosis. Using targeted lipidomics as a discovery tool, our current research efforts have identified molecules involved in the crosstalk between inflammatory responses and cellular metabolism, primarily engaging the endoplasmic reticulum (ER) proteins. We are currently developing functional studies of protein modification by nitro-fatty acids to determine their physiological relevance and cellular effects. Additionally, we will determine, using genetic tools, the contributions by the targeted ER proteins and explore new roles on inflammation, energy metabolism, and tissue fibrosis in preclinical models of obesity, diabetes, and cardiovascular diseases.
   
   
3. Non-invasive quantitative imaging analysis of tissue pathology. We are highly interested in developing and applying non-invasive imaging approaches for tissue pathology diagnosis, including quantitative analysis of lipid accumulation and fibrosis. We have recently applied photoacoustic-ultrasound imaging for NAFLD diagnosis aiming to mimic the ideal clinical scenario, which involves avoiding liver biopsy. More recently, we have applied in vivo imaging for quantitative analysis of endometriosis lesion formation in preclinical syngeneic models. We are currently exploring other imaging modalities such as modified MRI approaches for quantitative analysis of tissue fibrosis.

Publications

• Chang, F., Gunderstofte, C., Colussi, N., Pitts, M., Salvatore, S. R., Thielke, A. L., Turell, L., Alvarez, B., Goldbach-Mansky, R. Villacorta, L. Holm, C. K., Schopfer, F. J., & Hansen A. L. (2024). Development of nitroalkene-based inhibitors to target STING-dependent inflammation. Redox Biology 74:103202.
• Rom, O., Xu, G., Guo, Y., Zhu, Y., Wang, H., Zhang, J., Fan, Y., Liang, W., Lu, H., Liu, Y., Aviram, M., Liu, Z., Kim, S., Liu, W., Wang, X., Chen, Y. E., & Villacorta, L. (2019). Nitro-fatty acids protect against steatosis and fibrosis during development of nonalcoholic fatty liver disease in mice. EBioMedicine, 41, 62-72.
• Villacorta, L., Minarrieta, L., Salvatore, S. R., Khoo, N. K., Rom, O., Gao, Z., Berman, R. C., Jobbagy, S., Li, L., Woodcock, S. R., Chen, Y. E., Freeman, B. A., Ferreira, A. M., Schopfer, F. J., & Vitturi, D. A. (2018). In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation. Redox Biology, 15, 522-531.
• Villacorta, L., Chang, L., Salvatore, S. R., Ichikawa, T., Zhang, J., Petrovic-Djergovic, D., Jia, L., Carlsen, H., Schopfer, F. J., Freeman, B. A., & Chen, Y. E. (2013). Electrophilic nitro-fatty acids inhibit vascular inflammation by disrupting LPS-dependent TLR4 signalling in lipid rafts. Cardiovascular Research, 98(1), 116-124.
• Chang, L., Villacorta, L., Li, R., Hamblin, M., Xu, W., Dou, C., Zhang, J., Wu, J., Zeng, R., & Chen, Y. E. (2012). Loss of Perivascular Adipose Tissue on Peroxisome Proliferator-Activated Receptor-gamma Deletion in Smooth Muscle Cells Impairs Intravascular Thermoregulation and Enhances Atherosclerosis. Circulation, 126(9), 1067-1078.

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Honors and Awards

• 2024: Endometriosis Foundation of America Research Award
• 2023: UL1TR002378 National Center for Advancing Translational Sciences: Regression of endometriosis burden and associated pain by novel STING inhibitors.
• 2019: Fellow of the American Heart Association
• 2016: Peer Review Steering Committee Volunteer Recognition Award: American Heart Association
• 2014: McKay Research Award, University of Michigan
• 2011: Scientist Development Award, American Heart Association
• 2008: Marie Curie Fellow