The Science Behind the Systems

An imaging and computational platform to study the physical and molecular determinants of gastrointestinal muscle injury

LABORATORY OVERVIEW

Gilbert Laboratory

The laboratory is focused on studying the physical and molecular determinants of gastrointestinal muscle injury. Towards this end, the laboratory has developed an imaging and computational platform to study the biology of architecturally complex muscular tissues, specifically embodying the following areas of inquiry:

Structural and biological determinants of adaptive and maladaptive remodeling in muscle, including cytokine-driven cellular plasticity, architectural disarray, and pathological mechanics.
Diffusion-based MR methods to image architectural injury through the interrogation of Q-space, a mathematical formalism defining the distribution of oriented cells in tissue across spatial scale.
Characterization of motion and force based on multiscale computational models of normal and pathological function derived from myoarchitecture, myofilament interactions, and energy utilization.
Methods to characterize and treat the immunopathology underlying gastrointestinal motility disorders.
Photon-induced energy conversion technology, featuring the use of nano-encapsulated photolytic energy to drive the formation of dissolved oxygen for metabolic perturbation and therapy.

Over two decades, this work has ranged from GI motility and smooth muscle disease to diffusion-based imaging systems, immune signaling, and oxygen delivery chemistry. Some ideas gained traction quickly. Others, especially those that redefined how fibroblasts, injury, and tissue architecture are understood, took years to publish. That is the nature of systems-based work: it does not always fit cleanly into categories, but it is often where the next wave of discovery begins.

Highlighted Contributions

Mapping Biological Architecture with Q-Space MRI

The laboratory conceived diffusional MRI methods, termed Q-Space MR imaging, to map the complex myoarchitecture of muscular organs in the human body. Early publications were among the first to describe how muscle fiber orientation, disarray, and microarchitecture might be visualized noninvasively (CV #95, CV #111). These papers laid the groundwork for a translational imaging platform now applied across several areas of inquiry, including muscle degeneration in aging, neuromuscular injury after radiation, and tongue structure as it relates to cognitive decline.

Architecture stores injury. That is the central advantage of Q-Space imaging: it allows examination of tissue architecture to see how damage has played out over time, revealing where structure fails before function does.

Architectural Design of the Mammalian Tongue

By classical definitions, the intrinsic musculature of the tongue is comprised of a core region of orthogonally related fibers, contained within a sheath of longitudinally oriented fibers, which are intricately merged with extrinsic fibers that, in the aggregate, modify shape, position, and patterns of tissue deformation. By this formulation, architectural understanding of the mammalian tongue during swallowing requires a conceptualization of how those structures affect bolus accommodation (coordinated contraction of intrinsic fibers) and propulsion (protraction/retraction exerted by the genioglossus, hyoglossus, and styloglossus).

Evolving concepts, however, suggest that lingual musculature is more accurately considered as a hierarchical array of myofibers, with the tissue defined simultaneously at the microscopic (single fiber), mesoscopic (multi-fiber arrays), and macroscopic (tissue) scales. To illustrate the concept of architectural assembly, the laboratory has demonstrated the explicit geometric relationships that exist among these fiber populations in the context of the mouse tongue, obtained through Q-Space MRI with tractography and successive co-registration of previously segmented muscle fiber populations.

Multiscale Model of Skeletal and Cardiac Muscle Mechanical Function

This research defined the manner in which the distributed material and contractile elements of muscular organs, such as the tongue or the heart, contribute to motion. Using neural network-enhanced myoarchitecture, finite element modeling, and the Huxley myofilament model, the laboratory derived bolus flow profiles from tongue mechanics and extended the framework to cardiac function.

Phosphoregulation of Cardiac Myoarchitecture

The laboratory investigated the role of phosphorylation in maintaining cardiac myoarchitectural integrity, demonstrating how the phosphorylation state of myosin-binding protein C3 (MYBPC3) modulates sarcomere stability. These findings contribute to the broader understanding of how molecular-level regulatory events propagate to organ-scale structural and functional consequences in the diseased heart.

Fibroblast Transdifferentiation & Inflammofibrotic Muscle Injury

The laboratory developed a model of muscle injury that embodies the distributed effects of differentiated and transdifferentiated fibroblasts, sarcomere proteins, and immune cells. A pivotal finding, published in Communications Biology (Nature Portfolio) in 2023, demonstrated that resident cardiac fibroblasts were expressing markers typically associated with immune cells. These were not inflammatory cells migrating in; they were resident cells changing phenotype (CV #111).

That distinction changes the understanding of how inflammation and repair actually occur. It suggests that chronic inflammation is not always driven by external immune cells but may arise from local support cells reprogramming themselves in response to stress or injury. That insight has reshaped the laboratory’s approach to everything from muscle aging to GI inflammation, and the work now serves as a reference point for scientists studying tissue plasticity and disease progression.

Photocatalysis & Regulation of Biological Redox Chemistry

Life on Earth is defined by seminal relationships involving oxygen, water, and energy. To support living systems, Nature has evolved mechanisms to generate oxygen from the most basic physical components, namely water and sunlight. Recalling Nature’s solution to life support, photons of solar light are characteristically absorbed by endogenous chromophores during photosynthesis, followed by the displacement of electrons across energy bands, resulting in the generation of positively charged electron holes and the separation of electrical charge. The presence of strong surface charge separation promotes the splitting of water into oxygen and hydrogen. The effectiveness by which biological systems generate and utilize oxygen can be considered a design template upon which artificial systems may be created.

With this understanding, the laboratory established a technology that emulates the capacity of plants to extract dissolved oxygen from water in the unique and highly significant setting of whole blood, thereby allowing, for the first time, oxygenation of hemoglobin without the need for oxygen delivery via the lungs.

The core technology utilizes a semiconducting metal oxide material (TiO₂) as both the photo-absorption element and the mechanism mediating oxygen generation: UV light is absorbed by the TiO₂ layer, energizing the material through charge separation; electron vacancies drive the conversion of adjacent water to generate an active oxygen intermediate, which immediately disproportionates into dissolved oxygen (DO) and H₂O; DO diffuses from a high concentration at the surface into the adjacent fluid; liberated electrons are collected at the anode to avoid recombination; and liberated H⁺ combines with CO₂ at the cathode to form stable hydrocarbons. The concept of photolytic life support was described in the initial patent (U.S. Patent 7485261) and then expanded upon by subsequent NIH-funded research (RO1 HL 086652), establishing a microfluidic-scale photocatalytic respiratory device (U.S. Patent submitted).

Immunopathogenesis of Gastrointestinal Motility Disorders

The laboratory has conceived a model by which transdifferentiated fibroblasts and immune cells promote adverse remodeling of the neuroimmune interface and thereby affect oscillatory myoelectrical activity in the gastric wall. This 2022 publication (CV #110) introduced a new framework for understanding stomach motor control and its relationship to malnutrition, extending the laboratory’s fibroblast transdifferentiation findings into the gastrointestinal domain.

FROM IDEA TO IMPACT

Selected Timeline of Contributions

The following represents selected breakthroughs from the laboratory’s publication record, with reference to the academic CV where noted.

Year	Breakthrough	Impact
2007	Photocatalytic oxygen generation (CV #67)	Sparked Oxygen, Inc. platform for lung-free oxygenation
2010–2015	Q-Space MRI and fibroblast cytokine production (CV #79, #89, #95)	Changed how we visualize aging, structure, and immune signaling
2016	Q-Space MRI in heart failure (CV #95)	Validated architectural imaging across organ systems
2022	Immune-driven gastric motility model (CV #110)	Introduced new view of stomach control and malnutrition
2023	Fibroblast identity reprogramming (CV #111)	Rewrote understanding of chronic inflammation
2024 (In Review)	Discovery of a new tongue muscle via Q-Space MRI	Uncovered functional anatomy with imaging alone

EXPLORE THE WORK

View the Work

Selected publications are available by topic. The full academic CV is available for download.