About

Virginia L. Ferguson is a Professor and the Hudson Moore Jr. Chair in Engineering at the Paul M. Rady Mechanical Engineering Department within the College of Engineering and Applied Science at the University of Colorado Boulder. She serves as Associate Chair for Research and specializes in the nano-scale characterization of materials and biological tissue. Her research focuses on soft-hard tissue interface mechanics, nano- and micro-indentation of bone, soft tissues, and hydrogels for tissue regeneration, and how aging, disuse, and metabolic disease impact the quality of materials that comprise bone and other musculoskeletal tissues. Dr. Ferguson's laboratory draws inspiration from biological materials and structures to develop novel engineered materials, utilizing advanced manufacturing techniques for tissue regeneration. She has led significant initiatives including two National Science Foundation Major Research Instrumentation awards, establishing the MIMIC core facility to enable multimodal imaging and multiscale mechanical characterization of materials.

Research topics

• Medicine
• Biology
• Biomedical engineering
• Cell biology
• Nanotechnology
• Engineering
• Computer Science
• Internal medicine
• Anatomy
• Materials science
• Chemistry
• Endocrinology
• Composite material
• Physics
• Physiology
• Environmental health

Selected publications

• Demystifying machine learning approaches in digital bone imaging using microCT and HRpQCT

  Bone Reports · 2026-04-06 · 1 citations

  articleOpen access

  Microcomputed tomography (microCT) and high-resolution peripheral quantitative computed tomography (HRpQCT) generate three-dimensional digital images capturing bone structure and quality. Radiomic analytical approaches applied to these images extract quantitative measures of bone microarchitecture (e.g., bone volume and density). Automating and interpreting radiomics data using conventional image analysis techniques (e.g., bone segmentation) and statistical approaches is often inadequate due to their limited capacity to accommodate complex, nonlinear relationships. These limitations are especially apparent in bone research when integrating imaging outcomes with results from complementary analytical methods (e.g., biomechanics and histology) and experimental factors (e.g., clinical data). Machine learning (ML) offers opportunities in bone research by leveraging powerful computational tools; for example, to enhance bone spatial resolution, accelerate digital image segmentation, and reveal hidden patterns and relationships within high-dimensional bone data. Insights into key ML model inputs, which may be interpreted as primary biological phenotypes or therapeutic targets, can be revealed using standard (i.e., parametric and non-parametric analyses) or advanced statistical methods (i.e., dimensionality reduction and data integration). Overall, this narrative review has three main objectives: (1) to introduce current applications of ML in preclinical and clinical bone research using microCT and HRpQCT; (2) synthesize the interconnectedness of the field of bone and machine learning through user-friendly scientometric and bibliometric analyses and visualization using a novel software called SciNetX; and (3) to provide an accessible, high-level understanding of how ML models are developed and interpreted. These elements aim to provide a foundational guide to incorporating ML into bone research using digital imaging techniques. • Machine Learning (ML) aids in digital bone imaging with microCT and HRpQCT • ML is used for bone visualization, segmentation, prediction, classification, and clustering • Standard and advanced radiomic metrics of bone microarchitecture can be evaluated simultaneously using ML • Interpretable ML approaches enable the identification of biologically informative and actionable disease imaging patterns in bone health • This high-level narrative review, coupled with a novel scientometric and bibliometric analytical software called SciNetX, highlights ML approaches for digital bone imaging

  PublisherDOI

• ADAR1 haploinsufficiency and sustained picornaviral RdRp dsRNA synthesis synergize to dysregulate RNA editing and cause multi-system interferonopathy

  mBio · 2025-07-22 · 2 citations

  articleOpen access

  ABSTRACT Sensing of viral double-stranded RNA (dsRNA) by MDA5 triggers abundant but transient interferon-stimulated gene (ISGs) expression. If dsRNA synthesis is made persistent by transgenically expressing a picornaviral RNA-dependent RNA polymerase (RdRp) in mice, lifelong MDA5-MAVS pathway activation and marked, global ISG upregulation result. This confers robust protection from viral diseases, but in contrast to numerous other chronic MDA5 hyperactivation states, the mice suffer no autoimmune or other health consequences. Here, we find that they further confound expectations by being resistant to a strong autoimmunity (lupus) provocation. However, knockout of one allele of Adar breaks the autoinflammation-protected state of RdRp tg mice and results in a severe disease that resembles interferonopathies caused by MDA5 gain-of-function protein mutations. Adar +/– mice are healthy, but Adar +/– RdRp tg mice have shortened lifespan, stunted growth, premature fur graying, poorly developed teeth, skeletal abnormalities, and extreme ISG elevations. A-to-I edits are both abnormally distributed and increased (numbers of genes and sites). These results, with a nucleic acid-triggered and MDA5-wild-type model, illuminate the ADAR1-MDA5 axis in the regulation of innate immunity and establish that viral polymerase-sourced dsRNA can drive autoinflammatory disease pathogenesis. IMPORTANCE RNA virus double-stranded RNAs (dsRNAs) are important pathogen-associated molecular patterns that are sensed by the RIG-I-like receptor MDA5, which triggers an acute innate immune response involving many interferon-stimulated genes (ISGs). One key to a healthy innate immune system is that MDA5 does not sense endogenous dsRNA. This is normally ensured by dsRNA duplex-disrupting ADAR1 editing of host dsRNAs. Picornavirus RdRp tg mice have an unusual constitutive MDA5 activation state, with very high lifelong MDA5-mediated ISG expression that confers robust protection from diverse lethal viruses. Importantly, and in contrast to numerous other chronic MDA5 hyperactivation states, the mice develop no autoinflammatory consequences. If we delete one ADAR1 allele, however, which by itself is well tolerated, the mice develop a multisystem disease that resembles the human interferonopathy Singleton-Merten syndrome. In contrast to other MDA5/ADAR1 disease models, the MDA5 and ADAR1 proteins are both wild type in this dsRNA-driven model.

  PublisherDOI

• Simulated microgravity accurately models long-duration spaceflight effects on bone and skeletal muscle in skeletally immature mice

  Bone Reports · 2025-08-18 · 2 citations

  articleOpen access

  Spaceflight (SF) and disuse result in decreases in bone and skeletal muscle volume that increase fracture risk. Hindlimb unloading (HLU) has been widely used to model the effects of microgravity. However, the effects of SF and HLU on bone and skeletal muscle have not been directly compared during long-duration SF. We examined the effects of five weeks of SF and HLU in the femurs of female Balb/c mice. For the first time, SF and HLU were directly compared using mice of the same age, strain, sex, and duration as a mission to the ISS. We hypothesized that HLU would accurately model SF, resulting in similar bone and skeletal muscle loss. Ten-week old female Balb/c mice were assigned to baseline, vivarium control, habitat control, and SF groups (n = 10/group). A separate cohort of 10-week female Balb/c mice were placed in HLU or control (n = 10/group). Femoral cortical area increased from baseline in all groups except HLU. The magnitudes of increases were lower in the SF and HLU groups. Similar effects were seen in trabecular bone. Femoral ultimate force decreased in SF and HLU groups, compared to control groups. Gastrocnemius and quadriceps mass was lower in SF and HLU mice than in control mice. HLU resulted in greater bone loss than SF, possibly due to differences in housing conditions. HLU effectively models long-duration effects of SF on the musculoskeletal system, highlighting its utility for studying astronaut health risks and developing countermeasures. • Hindlimb unloading accurately models the effects of long-duration spaceflight on bone and skeletal muscle mass in growing mice. • Cage style impacts bone and skeletal muscle, highlighting the need for maintaining the same cage in spaceflight and ground control animals. • Spaceflight and hindlimb unloading attenuate increases in cortical bone mass and bone strength that occur during skeletal development.

  PublisherDOI

• Ketogenic Diet Causes Bone Loss in Growing and Adult Mice and Reduces the Skeletal Response to Exercise

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Fiber Type and Stimulus Determine Progression of Skeletal Muscle Atrophy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-14

  preprintOpen access

  Background: Skeletal muscle atrophy is prevalent worldwide and is a major detractor from length and quality of life. It is often diagnosed and treated as a single disorder, but the causal stimuli and progression of atrophy vary widely. Malnutrition and disuse are two common causes of muscle atrophy, and despite their prevalence and extensive characterization, there have been no direct comparisons of how these two types of atrophy progress and whether they differentially affect skeletal muscle fiber types. The purpose of this study is to directly compare atrophy from fasting and disuse and provide a transcriptomic resource for future research on both conditions. Methods: We fasted or hindlimb suspended (HS) two cohorts of 12-week-old female C57/bl6 mice. Mice were fasted for up to 72 hours to induce malnutrition atrophy or were hindlimb suspended for 0, 3, 7, 14, or 28 days to induce disuse atrophy. At each timepoint, mice were euthanized and three muscles (tibialis anterior (TA), extensor digitorum longus (EDL), and soleus) were weighed and collected for RNA sequencing. Atrophy progression and gene expression changes were compared across muscle fiber types and atrophy stimuli. Results: We found differences in atrophy progression between muscle fiber types based on fiber twitch speed and atrophy stimulus. Fasted mice lost 25% of their body weight and 23% of fast-twitch TA mass with little change in soleus. In contrast, HS mice lost 40% of the slower-twitch soleus but the effect on the TA was negligible. Gene expression varied in response to both atrophy stimuli, but a greater number of genes changed with fasting compared to HS in the EDL and soleus. By muscle type, a greater transcriptional shift occurred in the EDL with fasting while the soleus showed more gene changes during HS. Enrichment analysis of transcriptional changes showed similarities (downregulation in muscle growth pathways) and differences (increased fatty acid metabolism in fasting and increased neuronal activity in HS) between atrophy stimuli. Conclusions: Atrophy progression varies based on stimuli and muscle fiber type. This study provides a large, matched data set where the effects of different atrophic stimuli can be easily and directly compared in multiple fiber types. To our knowledge, this is the first study to closely compare these two atrophy stimuli in a muscle type-specific context. This work demonstrates that atrophy is not a single disorder and that the development of therapies may need to be tailored to the atrophic stimulus.

  PublisherOA PDFDOI

• ADAR1 haploinsufficiency and sustained viral RdRp dsRNA synthesis synergize to dysregulate RNA editing and cause multi-system interferonopathy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-22

  preprintOpen access

  Sensing of viral double-stranded RNA by MDA5 triggers abundant but transient interferon-stimulated gene (ISGs) expression. If dsRNA synthesis is made persistent by transgenically expressing a picornaviral RNA-dependent RNA polymerase (RdRp) in mice, lifelong MDA5-MAVS pathway activation and marked, global ISG upregulation result. This confers robust protection from viral diseases but in contrast to numerous other chronic MDA5 hyperactivation states, the mice suffer no autoimmune or other health consequences. Here we find they further confound expectations by being resistant to a strong autoimmunity (lupus) provocation. However, knockout of one allele of Adar breaks the autoinflammation-protected state of RdRptg mice and results in a severe disease that resembles interferonopathies caused by MDA5 gain-of-function protein mutations. Adar+/- mice are healthy but Adar+/- RdRptg mice have shortened lifespan, stunted growth, premature fur graying, poorly developed teeth, skeletal abnormalities, and extreme ISG elevations. A-to-I edits are both abnormally distributed and increased (numbers of genes and sites). These results, with a nucleic acid-triggered and MDA5-wild type model, illuminate the ADAR1-MDA5 axis in the regulation of innate immunity and establish that viral polymerase-sourced dsRNA can drive autoinflammatory disease pathogenesis.

  PublisherDOI

• Effect of pregnancy, vaginal delivery, postpartum remodeling, and age on the tensile behavior and biochemical composition of the murine ulterosacral ligament (USL)

  Acta Biomaterialia · 2025-07-05 · 3 citations

  articleSenior authorCorresponding
  PublisherDOI

• Integrative cartilage repair using acellular allografts for engineered structure and surface lubrication in vivo

  npj Regenerative Medicine · 2024-09-28 · 9 citations

  articleOpen access

  The repair of articular cartilage after damage is challenging, and decellularized tissue offers a possible treatment option to promote regeneration. Here, we show that acellular osteochondral allografts improve integrative cartilage repair compared to untreated defects after 6 months in an ovine model. Functional measures of intratissue strain/structure assessed by MRI demonstrate similar biomechanics of implants and native cartilage. Compared to native tissue and defects, the structure, composition, and tribology of acellular allografts preserve surface roughness and lubrication, material properties under compression and relaxation, compositional ratios of collagen:glycosaminoglycan and collagen:phosphate, and relative composition of types I/II collagen. While high cellularity was observed in bone regions and integration zones between cartilage-allografts, recellularization of chondral implants was inconsistent, with cell migration typically less than ~750 µm into the dense decellularized tissue, possibly limiting long-term cellular maintenance. Our results demonstrate the structural and biomechanical efficacy of acellular allografts for at least six months in vivo.

  PublisherOA PDFDOI

• Controlled Mechanical Property Gradients Within a Digital Light Processing Printed Hydrogel-Composite Osteochondral Scaffold

  Annals of Biomedical Engineering · 2024-04-29 · 18 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Altered post-fracture systemic bone loss in a mouse model of osteocyte dysfunction

  JBMR Plus · 2024-11-01 · 2 citations

  articleOpen access

  Femur fracture leads to loss of bone at uninjured skeletal sites, which may increase risk of subsequent fracture. Osteocytes, the most abundant bone cells, can directly resorb bone matrix and regulate osteoclast and osteoblast activity, but their role in systemic bone loss after fracture remains poorly understood. In this study we used a transgenic (TG+) mouse model that overexpresses human B-cell lymphoma 2 (BCL-2) in osteoblasts and osteocytes. This causes enhanced osteoblast proliferation, followed by disruption in lacunar-canalicular connectivity and massive osteocyte death by 10 wk of age. We hypothesized that reduced viable osteocyte density would decrease the magnitude of systemic bone loss after femur fracture, reduce perilacunar remodeling, and alter callus formation. Bone remodeling was assessed using serum biomarkers of bone formation and resorption at 5 d post-fracture. We used micro-computed tomography, high resolution x-ray microscopy, mechanical testing, and Raman spectroscopy to quantify the magnitude of systemic bone loss, as well as changes in osteocyte lacunar volume, bone strength, and bone composition 2 wk post-fracture. Fracture was associated with a reduction in circulating markers of bone resorption in non-transgenic (TG-) animals. TG+ mice exhibited high bone mass in the limbs, greater cortical elastic modulus and reduced post-yield displacement. After fracture, TG+ mice lost less trabecular bone than TG- mice, but conversely TG+ mice exhibited trends toward a lower yield point and reduced femoral cortical thickness after fracture, though these were not statistically significant. Lacunar density was greater in TG+ mice, but fracture did not alter lacunar volume in TG+ or TG- mice. These findings suggest that osteocytes potentially play a significant role in the post-traumatic systemic response to fracture, though the effects differ between trabecular and cortical bone.

  PublisherOA PDFDOI

Recent grants

• MRI Acquisition: An integrated platform for combined multi-scale mechanical and chemical analysis to inform functional materials design

  NSF · $434k · 2013–2015

• NIH Grant R21AR06979101A1

  NIH · $156k · 2019

• CAREER: Reverse-Engineering the Bone-Cartilage Interface for Successful Joint Repair - Coupled with a New Program to Promote Diversity in Rehabilitative Bioengineering

  NSF · $445k · 2011–2017

• NIH Grant R21AR069791

  NIH · $189k · 2020

• NIH Grant R21HD090696

  NIH · $417k · 2019

Frequent coauthors

• Louis Stodieck

  University of Colorado Boulder

  42 shared

• Ted A. Bateman

  University of North Carolina at Chapel Hill

  33 shared

• Steven J. Simske

  Colorado State University

  32 shared

• A. Boyde

  Queen Mary University of London

  24 shared

• Kendall S. Hunter

  University of Colorado Anschutz Medical Campus

  23 shared

• Stephanie J. Bryant

  University of Colorado Boulder

  23 shared

• Michael J. Pecaut

  Loma Linda University

  17 shared

• Daila S. Gridley

  Loma Linda University

  17 shared

Awards & honors

• American Institute for Medical and Biomedical Engineering Co…
• Hudson Moore Endowed Professor, College of Engineering and A…
• Faculty Success Program, FSP, National Center for Faculty De…
• Innovative Grant Program Recipient for Inflammation-Induced…
• BOLD Center Faculty Fellow, College of Engineering and Appli…