Leon Gabriel Straub
Primary Appointment
Research Assistant Professor, Pharmacology
Research Disciplines
Biochemistry, Metabolism, Molecular Biology, Translational Science
Research Interests
Research Assistant Professor of Pharmacology
Research Description
My research program in the Department of Pharmacology at the University of Virginia focuses on understanding how adipose tissue dysfunction, metabolic signaling, and immune–stromal interactions drive human disease, and on developing targeted therapeutic strategies that directly address these mechanisms. My work combines mechanistic physiology, transcriptomics, and gene-therapy approaches to define disease pathways with a level of resolution that supports both biological insight and clinical translation.
A central focus of my work is the development of tissue-specific AAV-based interventions for metabolic disease. Building on prior work demonstrating that adipose tissue signaling profoundly shapes systemic glucose homeostasis, I am developing strategies that allow precise control of metabolic pathways in adipocytes and cardiomyocytes. These studies include gene-therapy approaches to counteract oxidized-lipid–driven cardiac dysfunction as well as adipocyte-targeted modulation of incretin pathways to improve glucose tolerance and energy balance. Together, these efforts aim to establish new mechanistic links between adipose tissue biology, metabolic resilience, and cardiometabolic health.
In parallel, I investigate the molecular basis of lipedema, a poorly understood adipose-tissue disorder that lacks both molecular diagnostic criteria and druggable targets. Through multi-center collaborations, I integrate harmonized RNA-sequencing datasets with advanced statistical modeling to identify reproducible gene-expression programs that distinguish lipedema from obesity and lymphedema. These analyses point toward distinct immunometabolic and extracellular-matrix remodeling processes and form the basis for the development of predictive transcriptomic tools for clinical use. My goal is to translate these mechanistic insights into objective diagnostic strategies and, ultimately, targeted therapeutic approaches.
Across these projects, my research leverages rigorous quantitative methods to define how local perturbations in adipose tissue shape systemic physiology. I am committed to building a research environment that promotes collaboration, supports trainees, and advances the department’s mission to develop mechanistically grounded therapies that improve human health.
Personal Statement
A central focus of my work is the development of tissue-specific AAV-based interventions for metabolic disease. Building on prior work demonstrating that adipose tissue signaling profoundly shapes systemic glucose homeostasis, I am developing strategies that allow precise control of metabolic pathways in adipocytes and cardiomyocytes. These studies include gene-therapy approaches to counteract oxidized-lipidâdriven cardiac dysfunction as well as adipocyte-targeted modulation of incretin pathways to improve glucose tolerance and energy balance. Together, these efforts aim to establish new mechanistic links between adipose tissue biology, metabolic resilience, and cardiometabolic health.
In parallel, I investigate the molecular basis of lipedema, a poorly understood adipose-tissue disorder that lacks both molecular diagnostic criteria and druggable targets. Through multi-center collaborations, I integrate harmonized RNA-sequencing datasets with advanced statistical modeling to identify reproducible gene-expression programs that distinguish lipedema from obesity and lymphedema. These analyses point toward distinct immunometabolic and extracellular-matrix remodeling processes and form the basis for the development of predictive transcriptomic tools for clinical use. My goal is to translate these mechanistic insights into objective diagnostic strategies and, ultimately, targeted therapeutic approaches.
Across these projects, my research leverages rigorous quantitative methods to define how local perturbations in adipose tissue shape systemic physiology. I am committed to building a research environment that promotes collaboration, supports trainees, and advances the departmentâs mission to develop mechanistically grounded therapies that improve human health.
Selected Publications
Straub, L. G., & Scherer, P. E. (2022). Insulin sensitive human adipocytes for in vitro studies. Nature Reviews Endocrinology, 18(10), 591-592. PMID: 35896823 DOI: 10.1038/s41574-022-00727-x
Straub, L. G., Efthymiou, V., Grandl, G., Balaz, M., Challa, T. D., Truscello, L., ... & Wolfrum, C. (2019). Antioxidants protect against diabetes by improving glucose homeostasis in mouse models of inducible insulin resistance and obesity. Diabetologia, 62(11), 2094-2105. PMID: 31309261 DOI: 10.1007/s00125-019-4937-7
Heine, M., Fischer, A. W., Schlein, C., Jung, C., Straub, L. G., Gottschling, K., ... & Heeren, J. (2018). Lipolysis triggers a systemic insulin response essential for efficient energy replenishment of activated brown adipose tissue in mice. Cell metabolism, 28(4), 644-655. PMID: 30033199 DOI: 10.1016/j.cmet.2018.06.020
Grandl, G., Straub, L., Rudigier, C., Arnold, M., Wueest, S., Konrad, D., & Wolfrum, C. (2018). Shortâterm feeding of a ketogenic diet induces more severe hepatic insulin resistance than an obesogenic highâfat diet. The Journal of physiology, 596(19), 4597-4609. PMID: 30089335, DOI: 10.1113/JP275173
Moser, C., Straub, L. G., Rachamin, Y., Dapito, D. H., Kulenkampff, E., Ding, L., ... & Wolfrum, C. (2021). Quantification of adipocyte numbers following adipose tissue remodeling. Cell Reports, 35(4). PMID: 33909996 DOI: 10.1016/j.celrep.2021.109023
Challa, T. D., Dapito, D. H., Kulenkampff, E., Kiehlmann, E., Moser, C., Straub, L., ... & Wolfrum, C. (2020). A genetic model to study the contribution of brown and brite adipocytes to metabolism. Cell Reports, 30(10), 3424-3433. PMID: 32160547 DOI: 10.1016/j.celrep.2020.02.055
Modica, S., Straub, L. G., Balaz, M., Sun, W., Varga, L., Stefanicka, P., ... & Wolfrum, C. (2016). Bmp4 promotes a brown to white-like adipocyte shift. Cell reports, 16(8), 2243-2258. PMID: 27524617 DOI: 10.1016/j.celrep.2016.07.048
Behrens, J., Braren, I., Jaeckstein, M. Y., Lilie, L., Heine, M., … Straub, L. G., ... & Scheja, L. (2024). An efficient AAV vector system of Rec2 serotype for intravenous injection to study metabolism in brown adipocytes in vivo. Molecular Metabolism, 88, 101999. PMID: 39094948 DOI: 10.1016/j.molmet.2024.101999
Lebek, S., Caravia, X. M., Straub, L. G., Alzhanov, D., Tan, W., Li, H., ... & Olson, E. N. (2024). CRISPR-Cas9 base editing of pathogenic CaMKIIδ improves cardiac function in a humanized mouse model. The Journal of Clinical Investigation, 134(1). PMID: 37856214 DOI: 10.1172/JCI175164
Straub, L. G., Funcke, J. B., Joffin, N., Joung, C., Al-Ghadban, S., Zhao, S., ... & Scherer, P. E. (2025). Defining lipedema's molecular hallmarks by multi-omics approach for disease prediction in women. Metabolism, 168, 156191. PMID: 40097137 DOI: 10.1016/j.metabol.2025.156191