Improving health through musculoskeletal modeling.
About Us
The Multiscale Muscle Mechanophysiology (“M3”) lab is collectively fascinated by skeletal muscles, which are the motors for all the wide range of voluntary movements in the human body. Each muscle’s properties are beautifully tuned for a specific function in the body, which can be easily disrupted by diseases such as muscular dystrophy, cerebral palsy, or in aging populations. We seek to gain new insights into the form, function, biology, and diseases of muscles. Our work has the ultimate goal of improving treatments and quality of life for individuals suffering from muscle-related clinical problems. We integrate a variety of computational and experimental approaches to achieve this goal.
Below are some of the current applications of our work. Check out our publications for more information on current and past projects.
Cellular and Tissue
Muscle
Whole Body
OUR TEAM
Silvia Blemker, PhD
Principal Investigator
[email protected] Dr. Blemker is from Lawrence, Kansas. She did her undergraduate and Master’s work in Biomedical Engineering at Northwestern University, and her PhD in Mechanical Engineering at Stanford University. She is broadly interested in muscle mechanics & physiology, multi-scale modeling, mentoring students, and teaching. Her hobbies include: spending time with family, organizing legos, jogging, hiking, reading, traveling, and tennis (at the very beginner level).
Xiao Hu, PhD
Research Scientist
[email protected] Xiao completed his Ph.D. in Biomedical Engineering at Northwestern University. He is interested in using musculoskeletal modeling and simulation as a tool to understand how muscles are being used by our body to complete a variety of tasks and sports, and how this amazing ability is negatively affected by various musculoskeletal injuries and disorders. He likes watching movies, listening to music, playing ping-pong and spending time with his family.
Emily McCain, PhD
Postdoctoral Researcher
[email protected] Emily completed her Ph.D. in Mechanical Engineering at North Carolina State University in 2021 where she researched the consequences of neuromuscular and orthopedic impairments on walking performance. She is currently working toward the development of sex-specific musculoskeletal models to investigate how sex differences affect muscle function during movement. Outside of work, Emily enjoys spending time with her family, trying new restaurants around Charlottesville, camping, hiking, and watching the US women’s national soccer team play.
Matthew DiSalvo, PhD
Postdoctoral Researcher
[email protected] Matthew completed a B.S. in Bioengineering from Lehigh University in 2016 and a M.S. in Biomedical Engineering from Duke University in 2018. Currently, he is working on creating finite element models of muscle can be used in the design of regenerative therapies. When not in the lab, Matthew enjoys playing board games, brewing his own beer, and exploring the hiking trails around Charlottesville.
Allie McCrady, PhD
Postdoctoral Researcher
[email protected] Allie received her B.S. in biomedical engineering from Trine University in May 2019. Her research focuses on using ultrasound in clinic to investigate changes to skeletal muscle architecture in neuromuscular diseases and leveraging 3-D muscle modeling to improve the accuracy and reliability of ultrasound measurements. Outside the lab, Allie enjoys watching reality TV and Grey’s Anatomy, spoiling her two cats, exploring Charlottesville, and attending UVA sporting events!
Megan Haase
PhD Candidate
[email protected] Megan received her B.S. in Biomedical and Health Sciences Engineering from the joint department at North Carolina State and University of North Carolina Chapel Hill in May 2020. Her research focuses on using experimental and computational approaches to understand sex differences in muscle regeneration and hypertrophy. In her free time, Megan enjoys running, hiking, and playing piano.
Mario Garcia
PhD Candidate
[email protected] Mario completed a B.S. in Biomedical and Health Sciences Engineering with a minor in Philosophy from the joint department at North Carolina State and the University of North Carolina Chapel Hill in May 2021. His research interests focus on modeling muscle architecture using a combination of imaging modalities. Outside of the lab, Mario enjoys reading, running with friends, and spending time with his two dogs.
Kimberly Steininger
PhD Student
[email protected] Kimberly completed her B.S. in mechanical engineering and B.M. in flute performance at Boston University in January 2021. Her research interests include investigating muscle architectural changes and understanding how fat infiltration patterns influence the mechanics of muscle to better predict atrophy and disease progression. In her free time, Kimberly enjoys listening to and playing music, running, spending time outdoors, and watching Korean dramas.
Yasmina Zeineddine
PhD Student
[email protected] Yasmina graduated from VCU in 2022 with a B.S. in Biomedical Engineering. In the M3 lab, she is researching how chronic disuse of skeletal muscles influences regeneration following injury. Outside of the lab, Yasmina enjoys reading, crocheting, trying to keep her plants alive, and cooking.
Amanda Knizley
PhD Student
[email protected] Amanda received her B.S. in Biomedical and Health Sciences Engineering from the joint department at the University of North Carolina at Chapel Hill and North Carolina State University in May 2023. Her research focuses on using imaging and computational tools to visualize and analyze pelvic floor muscle dysfunction/injury in women. Outside of lab, Amanda enjoys sketching, singing/playing piano, and biking.
Jacob Dunn
Lab Specialist
[email protected] Jacob earned a B.S. in Biology with a minor in Medical Humanities from Baylor University in May 2020. His work in lab supports the research currently underway using experimental and computational approaches to understand sex differences in muscle physiology. Outside of the lab, Jacob enjoys reading, coffee, and leatherworking.
Mr. Bones
Lab Mascot
Be Part
Of Our
Story!
Opportunities
Prospective Graduate Students
Prospective graduate students interested in joining our research group should apply to our BME graduate program here or contact Dr. Silvia Blemker.
Undergraduates
Bright, hard-working undergraduates interested in working in the lab are invited to attend lab meetings for one semester to become familiar with our research before getting involved with a project. To be considered for a position, please email a cover letter and résumé to Dr. Silvia Blemker.
For difficulties accessing a publication, please contact Silvia Blemker
Contact Us
M3 Lab Address
415 Lane Road MR5 Room 2231 Box 800759 Charlottesville, VA 22903 (434)982-3329
Lab Director
Silvia Blemker, PhD Robert Thomson Distinguished Professor, Biomedical Engineering MR5 Room 2133 [email protected] (434)924-6291
Here's a map of the UVA hospital area. MR5 is building 20B, and parking is available in the 11th Street Parking Garage - Building 39.
Cellular and Tissue
Collagen Organization During Diaphragm Muscle Fibrosis in Duchenne Muscular Dystrophy
Duchenne muscular dystrophy is a devastating neuromuscular disease affecting 1 in 3500 boys, leading to severe muscle wasting
and accumulation of extracellular matrix (ECM) components during fibrosis. Despite extensive experimental research there remains no
effective treatment for this fatal disease and respiratory insufficiency is a leading cause of death. Fibrosis contributes to muscle
dysfunction but the structure and function of fibrotic tissue are largely uncharacterized. In this project we are interested in how
the organization of collagen, the key contributor to the tensile properties of the skeletal muscle ECM, influences diaphragm muscle
function during fibrosis.
At the ECM-level, we use imaging methods such as scanning electron microscopy (SEM) to visualize collagen structure and develop
finite-element models to determine the mechanical implications of changes in collagen structure during fibrosis. At the muscle-level,
we develop finite-element models to understand the complex effects of fibrotic tissue structure on damage susceptibility and muscle
tissue mechanics. Then we can couple these models with agent-based models to study the progression of fibrosis in dystrophic muscle,
particularly the relationships between ECM mechanics and dynamic cellular behaviors during fibrosis.
Modeling Cellular Behaviors During Muscle Regeneration
Computational models are an ideal complement to experimental efforts for understanding complex phenomena such as muscle degeneration,
regeneration, and remodeling, which emerge from the dynamic behaviors and interactions of individual, heterogeneous cells that are mediated
by numerous biochemical signals. While our fundamental understanding of the individual cellular and subcellular behaviors of muscle cells has
advanced, there remain no effective treatment methods to accelerate muscle regeneration and reduce fibrosis. In our lab, we use agent-based modeling
to study the impact of cell behaviors, cytokine expression, and sex hormones on muscle regeneration. These models are used to test variations
of growth factor levels to develop optimized treatments for muscle regeneration that account for variations in estrogen levels.
Project Members
Ridhi Sahani
PhD Candidate
Megan Haase
PhD Candidate
Muscle
Characterizing Muscle in Neuromuscular Disease
Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are devastating neuromuscular disorders
that occur in 1 in 11,000 live births and 1 in 6,000 boys, respectively. Recent pharmaceutical advances have revealed the
lack of sensitivity in current clinical functional assessments to functional changes in patients. Ultrasound has become a
common imaging modality to measure skeletal muscle architecture and quality due to its non-invasive nature and low cost; however,
a link between ultrasound measurements of muscle architecture and quality measurements to muscle function has not been well established.
In our lab, we are currently exploring the changes in architectural and qualitative parameters measured in muscle using ultrasound.
We are also working to understand how these changes relate to observed patient function. We plan to use these findings to develop an image-based
method to track functional changes in patients.
With the increasing popularity of ultrasound imaging in skeletal muscle, there are limitations to the data we can measure in the images.
We hope to use computational modeling and simulations to improve ultrasound imaging of muscle.
Project Members
Thanh (Vi) Tran, PhD
Postdoctoral Researcher
Matthew DiSalvo
PhD Candidate
Allie McCrady
PhD Candidate
Whole Body
Sex-Specific Modeling
Sex differences in musculoskeletal disease, injury, and aging create disparities in health care. Currently, musculoskeletal models are widely
used to study musculoskeletal diseases and injuries. However, these models primarily rely on: 1) data from male-only populations,
and/or 2) data that average measures from male and female populations, thus ignoring the sex differences that are known to exist in skeletal
anatomy, muscle architecture and strength. These profound limitations leave the field without essential tools to examine how sex differences
in musculoskeletal structure influence movement biomechanics, injury, and disease.
This project will resolve these serious limitations through three key aims. Aim 1 will use advanced imaging approaches to create a
first-of-its-kind digital database of musculoskeletal structure that characterizes the lower limbs of 50 female and 50 male subjects across a
wide range of body sizes. Aim 2 will incorporate this digital database into a computational framework that will create and validate a sex-specific
scaling approach for lower limb models. Aim 3 will utilize the models to examine how sex differences in musculoskeletal structure influence muscle
function and knee joint contact loads during two motor tasks: gait and landing biomechanics. Taken together, these aims will address critical questions
related to how sex differences impact movement biomechanics, injury susceptibility, injury recovery, and neuromuscular disease.
The work will also provide a rigorous, detailed, digital database of data and models that will be easy to use and openly accessible to the community.
DMD at Whole Body
Duchenne muscular dystrophy (DMD) is one of the most severe genetic diseases in humans, affecting 1 in 3,500 male births.
In DMD, dystrophin deficiency due to genetic mutations causes progressive muscle degeneration, in which muscles undergo necrosis,
fibrosis, and fat infiltration. Although dystrophin is deficient in all muscles, muscle degeneration progresses differently across muscles,
as indicated by the various amounts of fatty infiltration observed in imaging studies.
The lack of dystrophin in DMD causes dystrophic muscles to be vulnerable to mechanical stresses (the average force per unit area) developed
during contraction. Although previous animal studies have shown that eccentric contractions lead to damage to dystrophic muscles,
to what extent muscle contractions in daily physical activities contribute to disease progression in DMD remains unclear.
This project utilizes whole-body musculoskeletal modeling and simulation to understand muscle function during daily physical activities,
and how this function may contribute to disease progression in DMD. These understanding will provide a foundation to develop the guideline
of safe exercises for patients with DMD as well as assistive devices (e.g. exosuit) which prolong ambulation while minimizing muscle damage in
patients with DMD.
.jpg)
