About

Siobhan Craige, PhD, is an Assistant Professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech. Her research focuses on understanding how cells and tissues communicate to sense and respond to environmental changes such as diet, exercise, and disease. The central aim of her lab is to elucidate the molecular signaling mechanisms underlying the effects of diet and exercise, with specific emphasis on intercellular communication between endothelial cells and skeletal muscle cells in response to exercise stress, the impact of intra- and inter-cellular redox signaling on age-related changes in skeletal muscle, and the influence of high-fat diet-induced stress on sexually dimorphic redox responses in bone.

Research topics

• Biology
• Endocrinology
• Biochemistry
• Internal medicine
• Medicine
• Chemistry

Selected publications

• The Endothelium as Metabolic Conductor: Orchestrating Interorgan Metabolic Communication

  Circulation Research · 2026-05-21

  article1st authorCorresponding
  PublisherDOI

• The Endothelium as a Central Mediator of Exercise-Induced Metabolism and Communication – Corrigendum

  Exercise and Sport Sciences Reviews · 2026-03-10

  article1st authorCorresponding
  PublisherDOI

• The intersection of exercise, nitric oxide, and metabolism: Unraveling the role of eNOS in skeletal muscle and beyond

  Metabolism · 2025-07-30 · 7 citations

  reviewOpen accessSenior author

  Exercise protects against several diseases including cardiometabolic disorders. However, the molecular mechanisms driving these adaptations remain incompletely defined. Endothelial nitric oxide synthase (eNOS), a key source of nitric oxide (NO), is implicated in regulating glucose uptake, fatty acid metabolism, and mitochondrial remodeling in response to exercise. eNOS is expressed in both endothelial and non-endothelial cells and its effects on metabolism are multifaceted. Notably, eNOS is highly expressed in endothelial cells which are ubiquitous throughout all organ systems allowing them to closely integrate with surrounding cell types. This unique feature of the endothelium enables eNOS to influence both local microenvironments and signaling across organ systems. This review summarizes current findings on the role of eNOS-derived NO in exercise metabolism. Evidence suggests eNOS contributes to improved metabolic flexibility, enhanced mitochondrial function, and tissue crosstalk. However, data across experimental models remain mixed, with both supportive and conflicting results. Collectively, the literature indicates that eNOS plays a central, though context-dependent, role in facilitating exercise-induced metabolic benefits. Identifying the specific mechanisms and tissue contributions of eNOS activity remains an important area for future investigation, with potential relevance to metabolic disease prevention and treatment.

  PublisherDOI

• The Endothelium as a Central Mediator of Exercise-Induced Metabolism and Communication

  Exercise and Sport Sciences Reviews · 2025-10-23 · 2 citations

  articleOpen access1st authorCorresponding

  Cells lining the capillary endothelium, endothelial cells (ECs), play central roles in local and systemic metabolisms by sensing and responding to exercise-induced stresses. ECs release and respond to many factors, coordinating intra- and interorgan communication, supporting angiogenesis, and enhancing oxidative and global metabolism. Their widespread distribution positions them as key regulators of exercise-induced metabolic rewiring.

  PublisherDOI

• NOX4 Selectively Modulates Skeletal Muscle Mitochondrial Bioenergetic and Membrane Potential in a Substrate-Dependent Manner

  Free Radical Biology and Medicine · 2025-10-30

  articleSenior author
  PublisherDOI

• Distinct endothelial gene responses to acute exercise in skeletal muscle

  American Journal of Physiology-Endocrinology and Metabolism · 2025-08-11 · 3 citations

  articleOpen accessSenior authorCorresponding

  This study profiles the endothelial-specific transcriptional response to acute exercise at cell-type resolution. Comparative analysis with skeletal muscle fibers revealed distinct gene expression and upstream regulators. Key findings include endothelial-specific expression of exerkines, metabolic genes, and nitric oxide signaling. These results uncover a molecular basis for endothelial adaptation to exercise and suggest a potential role in mediating systemic exercise benefits.

  PublisherDOI

• Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency

  Redox Biology · 2025-06-06 · 2 citations

  articleOpen accessSenior authorCorresponding

  Reactive oxygen species (ROS) are critical mediators of cellular signaling that regulate metabolic homeostasis, including lipid uptake, synthesis, and storage. NADPH oxidase 4 (NOX4), a significant enzymatic source of ROS, has been identified as a redox-sensitive regulator of glucose and lipid metabolism. However, its contribution to sex-specific metabolic regulation remains poorly defined. This study compared how NOX4 knock-out (NOX4 KO) shifted systemic and tissue-specific metabolic phenotypes between male and female mice fed with a high-fat diet (HFD) for 20-weeks. We observed that male NOX4 mice on HFD exhibited reduced adiposity, diminished liver lipid accumulation, and improved glucose and insulin tolerance compared to male WT mice on HFD. In contrast, female NOX4 KO mice developed increased adiposity and lipid accumulation in peripheral adipose depots, accompanied by impaired glucose tolerance. Gene expression profiling in skeletal muscle and liver revealed distinct, sex-specific patterns of changes in genes related to lipid uptake, synthesis, and storage, possibly implicating differential activation of PPAR signaling pathways supportive of in vivo data. These findings identify NOX4 as a central regulator of sexually dimorphic lipid metabolism, acting through redox-sensitive transcriptional networks to shape divergent metabolic responses to HFD. • Male NOX4 KOs on HFD had less fat gain, better glucose handling, and lower liver fat • Female NOX4 KOs on HFD showed increased adiposity and glucose intolerance • Gene expression changes reveal sex-specific metabolic regulation by NOX4 • PPAR signaling may underlie sex-specific lipid responses to NOX4 KO • Findings suggest NOX4 signaling influences metabolism in a sex-dependent manner

  PublisherDOI

• The Role of Endothelial Nitric Oxide Synthase (eNOS) in Acute Exercise Adaptations within the Bone Marrow

  Free Radical Biology and Medicine · 2025-10-30

  articleSenior author
  PublisherDOI

• <scp>DECORIN</scp> , a triceps‐derived myokine, protects sorted β‐cells and human islets against chronic inflammation associated with type 2 diabetes

  Acta Physiologica · 2025-01-22 · 5 citations

  articleOpen access

  AIM: Pancreatic β-cells are susceptible to inflammation, leading to decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps-derived myokine, DECORIN, which plays a pivotal role in skeletal muscle-to-pancreas interorgan communication. However, whether DECORIN can directly impact β-cell function and susceptibility to inflammation remains unexplored. METHODS: The effect of DECORIN was assessed in sorted human and rat β-cell and human islets from healthy and type 2 diabetes (T2D) donors. We assessed glucose-stimulated insulin secretion (GSIS) and cytokine-mediated cell death. We then challenged sorted β-cells and human islets with inflammatory cytokines commonly associated with diabetes, such as tumor necrosis factor-α (TNF-α) alone or in combination with interleukin1-β (IL1-β) and interferon-γ (cytomix). RESULTS: DECORIN enhanced cell spreading and the localization of phosphorylated FAK at adhesions, promoting GSIS under basal conditions. It also increased insulin granule docking adhesion length and countered the inhibitory effects of TNF-α on adhesion and actin remodeling at the β-cell surface, resulting in preserved GSIS. DECORIN protected from cell death in sorted β-cells and islets challenged with TNF-α alone or TNF-α + cytomix. Interestingly, DECORIN increased both insulin content and secretion in human islets from T2D individuals. Additionally, DECORIN treatment reversed the impaired gene expression caused by T2D and enhanced the expression of genes essential for islet function and metabolism. CONCLUSION: Collectively, we have shown that DECORIN had a beneficial effect on human islets, protecting them from inflammation-induced cell death. In T2D islets, DECORIN restores islet function and reverses the expression of T2D-associated genes. Based on our data, we propose that DECORIN is a promising therapeutic target for diabetes-associated inflammation and diabetes itself.

  PublisherOA PDFDOI

• Endothelial Nitric Oxide Synthase: a Critical Mediator of Fatty Acid Oxidation during Energetic Stress in Skeletal Muscle

  Free Radical Biology and Medicine · 2025-10-30

  articleSenior author
  PublisherDOI

Recent grants

• Nox 4 modulation of NO bioavailability and vascular function

  NIH · $159k · 2010–2013

• Reactive oxygen species drive muscle metabolism

  NIH · $629k · 2019–2024

Frequent coauthors

• John F. Keaney

  Brigham and Women's Hospital

  37 shared

• Shashi Kant

  Harvard University

  30 shared

• Amada D. Caliz

  Brigham and Women's Hospital

  18 shared

• Yongmei Pei

  University of Massachusetts Chan Medical School

  11 shared

• Jacob Bond

  Virginia Tech

  11 shared

• Michaella M. Reif

  9 shared

• Adele Addington

  9 shared

• Kalyn S. Specht

  Virginia Tech

  9 shared

Awards & honors

• University Libraries Collaborative Research Grant (2023)
• HNFE S.J. Ritchey Fund for Faculty Pilot Studies (2023)
• VT Office of Undergraduate Research Faculty Grant + Suppleme…
• VT CALS Global Faculty Partnership Initiative Award (Institu…
• NIAMS K01 AR073332 (2019 – 2024)