Vlad Serbulea

GetPhoto.ashx?photo=vs9ck_1413
  • Phone: 4349240810

Primary Appointment

, Pharmacology

Education

  • BS, Chemistry and Biochemistry, University of California, Santa Barbara
  • PhD, Pharmacology, University of Virginia

Research Disciplines

Biochemistry, Cardiovascular Biology, Metabolism

Research Interests

Atherosclerosis, Redox Biology, Cellular Metabolism & Bioenergetics

Research Description

My graduate work investigated the link between adipose tissue inflammation and oxidative stress. Adipose tissue inflammation is an underlying cause of obesity-associated insulin resistance, affecting millions of people in the world. My work identified two classes of phospholipid oxidation products, using a novel liquid chromatography-mass spectrometry method, which drive macrophage polarization to an antioxidant or pro-inflammatory state, in lean and obese murine adipose tissue. These phospholipid classes have distinct effects on macrophage bioenergetics, which was recapitulated in adipose tissue macrophages found in lean and obese adipose tissue. The mechanisms of oxidized phospholipid action on macrophages were further characterized, paving the way for novel therapies for insulin resistance. As part of this work, I developed a novel mass spectrometry method for quantifying oxidized fatty acids in vivo.
My current work investigates the mechanisms governing smooth muscle cell phenotypic transitions during atherosclerosis, with the long-term goal of developing therapies that directly augment plaque stability. During the development of atherosclerotic lesions, smooth muscle cells phenotypically transition to a variety of detrimental, but also beneficial, cell types, including the plaque-stabilizing collagen-producing myofibroblast-like state. I have developed an in vitro model of the smooth muscle-to-myofibroblast transition. I am in the process of testing the role of smooth muscle cell metabolism plaque stability in vivo. More recently, I discovered that glucocorticoids play a major role in regulating the smooth muscle phenotypic transitions.

Selected Publications

2024

Shamsuzzaman, S., Deaton, R. A., Salamon, A., Doviak, H., Serbulea, V., Milosek, V. M., . . . Owens, G. K. (2024). Novel Mouse Model of Myocardial Infarction, Plaque Rupture, and Stroke Shows Improved Survival With Myeloperoxidase Inhibition.. Circulation. doi:10.1161/circulationaha.123.067931

2023

Genet, G., Genet, N., Paila, U., Cain, S. R., Cwiek, A., Chavkin, N. W., . . . Hirschi, K. K. (2024). Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia. CIRCULATION, 149(12), 944-962. doi:10.1161/CIRCULATIONAHA.122.062952

Chen, M., Shin, M., Ware, T. B., Donvito, G., Muchhala, K. H., Mischel, R., . . . Hsu, K. -L. (2023). Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 120(52). doi:10.1073/pnas.2304900120

Deaton, R. A., Bulut, G., Serbulea, V., Salamon, A., Shankman, L. S., Nguyen, A. T., & Owens, G. K. (2023). A New Autosomal Myh11-CreERT2 Smooth Muscle Cell Lineage Tracing and Gene Knockout Mouse Model-Brief Report. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 43(2), 203-211. doi:10.1161/ATVBAHA.122.318160

2022

Luse, M. A., Kruger, N., Good, M. E., Biwer, L. A., Serbulea, V., Salamon, A., . . . Isakson, B. E. (2022). Smooth muscle cell FTO regulates contractile function. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 323(6), H1212-H1220. doi:10.1152/ajpheart.00427.2022

Lempicki, M. D., Paul, S., Serbulea, V., Upchurch, C. M., Sahu, S., Gray, J. A., . . . Meher, A. K. (2022). BAFF antagonism via the BAFF receptor 3 binding site attenuates BAFF 60-mer-induced classical NF-?B signaling and metabolic reprogramming of B cells. CELLULAR IMMUNOLOGY, 381. doi:10.1016/j.cellimm.2022.104603

2021

Hartmann, F., Gorski, D. J., Newman, A. A. C., Homann, S., Petz, A., Owsiany, K. M., . . . Fischer, J. W. (2021). SMC-Derived Hyaluronan Modulates Vascular SMC Phenotype in Murine Atherosclerosis. CIRCULATION RESEARCH, 129(11), 992-1005. doi:10.1161/CIRCRESAHA.120.318479

Newman, A. A. C., Serbulea, V., Baylis, R. A., Shankman, L. S., Bradley, X., Alencar, G. F., . . . Owens, G. K. (2021). Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms. NATURE METABOLISM, 3(2), 166-+. doi:10.1038/s42255-020-00338-8

2020

Congdon, M., Fritzemeier, R. G., Kharel, Y., Brown, A. M., Serbulea, V., Bevan, D. R., . . . Santos, W. L. (2021). Probing the substitution pattern of indole-based scaffold reveals potent and selective sphingosine kinase 2 inhibitors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 212. doi:10.1016/j.ejmech.2020.113121

Senthivinayagam, S., Serbulea, V., Upchurch, C. M., Polanowska-Grabowska, R., Mendu, S. K., Sahu, S., . . . Leitinger, N. (2021). Adaptive thermogenesis in brown adipose tissue involves activation of pannexin-1 channels. MOLECULAR METABOLISM, 44. doi:10.1016/j.molmet.2020.101130

Seki, S. M., Posyniak, K., McCloud, R., Rosen, D. A., Fernandez-Castaneda, A., Beiter, R. M., . . . Gaultier, A. (2020). Modulation of PKM activity affects the differentiation of TH17 cells. SCIENCE SIGNALING, 13(655). doi:10.1126/scisignal.aay9217

Bories, G. F. P., Yeudall, S., Serbulea, V., Fox, T. E., Isakson, B. E., & Leitinger, N. (2020). Macrophage metabolic adaptation to heme detoxification involves CO-dependent activation of the pentose phosphate pathway. BLOOD, 136(13), 1535-1548. doi:10.1182/blood.2020004964

2019

Kruger, N., Biwer, L. A., Good, M. E., Ruddiman, C. A., Wolpe, A. G., DeLalio, L. J., . . . Isakson, B. E. (2020). Loss of Endothelial FTO Antagonizes Obesity-Induced Metabolic and Vascular Dysfunction. CIRCULATION RESEARCH, 126(2), 232-242. doi:10.1161/CIRCRESAHA.119.315531

Ahern, K. W., Serbulea, V., Wingrove, C. L., Palas, Z. T., Leitinger, N., & Harris, T. E. (2019). Regioisomer-independent quantification of fatty acid oxidation products by HPLC-ESI-MS/MS analysis of sodium adducts. SCIENTIFIC REPORTS, 9. doi:10.1038/s41598-019-47693-5

2018

Morioka, S., Perry, J. S. A., Raymond, M. H., Medina, C. B., Zhu, Y., Zhao, L., . . . Ravichandran, K. S. (2018). Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release. NATURE, 563(7733), 714-718. doi:10.1038/s41586-018-0735-5

Serbulea, V., Upchurch, C. M., Schappe, M. S., Voigt, P., DeWeese, D. E., Desai, B. N., . . . Leitinger, N. (2018). Macrophage phenotype and bioenergetics are controlled by oxidized phospholipids identified in lean and obese adipose tissue. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 115(27), E6254-E6263. doi:10.1073/pnas.1800544115

Meher, A. K., Spinosa, M., Davis, J. P., Pope, N., Laubach, V. E., Su, G., . . . Upchurch, G. R. J. (2018). Novel Role of IL (Interleukin)-1β in Neutrophil Extracellular Trap Formation and Abdominal Aortic Aneurysms. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 38(4), 843-853. doi:10.1161/ATVBAHA.117.309897

2017

Kerur, N., Fukuda, S., Banerjee, D., Kim, Y., Fu, D., Apicella, I., . . . Ambati, J. (2018). cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. NATURE MEDICINE, 24(1), 50-+. doi:10.1038/nm.4450

Serbulea, V., Upchurch, C. M., Ahern, K. W., Bories, G., Voigt, P., DeWeese, D. E., . . . Leitinger, N. (2018). Macrophages sensing oxidized DAMPs reprogram their metabolism to support redox homeostasis and inflammation through a TLR2-Syk-ceramide dependent mechanism. MOLECULAR METABOLISM, 7, 23-34. doi:10.1016/j.molmet.2017.11.002

Olmez, I., Brenneman, B., Xiao, A., Serbulea, V., Benamar, M., Zhang, Y., . . . Purow, B. (2017). Combined CDK4/6 and mTOR Inhibition Is Synergistic against Glioblastoma via Multiple Mechanisms. CLINICAL CANCER RESEARCH, 23(22), 6958-6968. doi:10.1158/1078-0432.CCR-17-0803

Dyballa-Rukes, N., Jakobs, P., Eckers, A., Ale-Agha, N., Serbulea, V., Aufenvenne, K., . . . Haendeler, J. (2017). The Anti-Apoptotic Properties of APEX1 in the Endothelium Require the First 20 Amino Acids and Converge on Thioredoxin-1. ANTIOXIDANTS & REDOX SIGNALING, 26(12), 616-629. doi:10.1089/ars.2016.6799

Serbulea, V., DeWeese, D., & Leitinger, N. (2017). The effect of oxidized phospholipids on phenotypic polarization and function of macrophages. FREE RADICAL BIOLOGY AND MEDICINE, 111, 156-168. doi:10.1016/j.freeradbiomed.2017.02.035

Jakobs, P., Serbulea, V., Leitinger, N., Eckers, A., & Haendeler, J. (2017). Nuclear Factor (Erythroid-Derived 2)-Like 2 and Thioredoxin-1 in Atherosclerosis and Ischemia/Reperfusion Injury in the Heart. ANTIOXIDANTS & REDOX SIGNALING, 26(12), 630-644. doi:10.1089/ars.2016.6795

2016

Wilkins, L. R., Brautigan, D. L., Wu, H., Yarmohammadi, H., Kubicka, E., Serbulea, V., . . . Haaga, J. R. (2017). Cinnamic Acid Derivatives Enhance the Efficacy of Transarterial Embolization in a Rat Model of Hepatocellular Carcinoma. CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, 40(3), 430-437. doi:10.1007/s00270-016-1515-y

Schaheen, B., Downs, E. A., Serbulea, V., Almenara, C. C. P., Spinosa, M., Su, G., . . . Ailawadi, G. (2016). B-Cell Depletion Promotes Aortic Infiltration of Immunosuppressive Cells and Is Protective of Experimental Aortic Aneurysm. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 36(11), 2191-+. doi:10.1161/ATVBAHA.116.307559