Orthopaedic Research Newsletter

April 2024

Advances in Mineral Metabolism Conference

AIMM 2024

April 8-12, 2024, Snowmass, CO 

Members of the Orthopaedic Research Laboratories joined other investigators at the Advances in Mineral Metabolism (AIMM)/ASBMR John Haddad Young Investigator Meeting in Snowmass, CO. Alex Knights received a prestigious John Haddad Young Investigator award for his work, Osteophyte formation in post-traumatic osteoarthritis. Ken Kozloff presented an invited lecture titled Bone stress injuries, wearable technology, and the quantifiable you. They were joined by Kurt Hankenson (former AIMM president) and Tristan Maerz, as well as members of the UM Dental School. 

Osteogenesis Imperfecta Foundation 

Annual Scientific Conference

OIF, Rosemont IL, April 17-19, 2024

Hsiao Sung and Ken Kozloff represented the Orthopaedic Research Laboratories at the 23rd Annual Osteogenesis Imperfecta Foundation Scientific Meeting. Hsiao Sung presented an invited lecture titled Sclerostin Antibody Therapy in Brtl/+ Maxillary and Femoral Bone in this annual meeting of scientists, clinicians, patients and advocates dedicated to the rare bone disease, Osteogenesis Imperfecta.

Congratulations!

Adam C. Abraham, Ph.D.

Research Investigator of Orthopaedic Surgery

Megan Killian, Ph.D.

Assistant Professor of Orthopaedic Surgery, and Molecular & Integrative Physiology

Associate Chair for Diversity, Equity, and Inclusion, Orthopaedic Surgery

Congratulations Dr. Abraham and Dr. Killian

R01 Award

Title:  Regulation of Tendon Enthesis Development and Healing via HIF1 

Funding: $2.6M by NIAMS

Duration: 5 years

Narrative: Achilles tendon ruptures are common musculoskeletal injuries, and the rate of rupture is rising with increased participation in sports. Vascular irregularities and degenerative changes to extracellular matrix (ECM) result in poor biomechanical properties that increase risk of tendon rupture. We have discovered that, following Achilles tendon rupture in mice, the tendon-bone enthesis exhibits profound cell loss, which impairs remodeling and further increases susceptibility to degeneration. This focal cell loss within the enthesis motivated our work to study enthesis cell survival during growth and following tendon injury. Our preliminary studies in mice have established the Achilles enthesis maintains a hypoxic niche during perinatal growth and depends on Hypoxia Inducible Factor-1a (HIF1a) for enthesis cell survival. Loss of Hif1a in tendon and enthesis progenitor cells leads to focal cell death, disruption of enthesis ECM, and failed integration of tendon into bone. Conversely, overexpression of Hif1a rescues cell within the enthesis following Achilles tendon injury, suggesting its potential role in guiding tendon and enthesis regeneration. Therefore, we hypothesize hypoxia is critical for establishing the enthesis progenitor cell/ECM niche, and cell survival in this niche depends on and is enhanced by Hif1a. Our central goal is to define HIF1-dependent mechanisms of cell function and ECM production during growth and repair of the fibrocartilage enthesis. We hypothesize that HIF1a drives enthesis cell differentiation in part by regulating cell survival and ECM deposition. Our long-term goal is to develop druggable therapeutics to prevent Achilles tendon rupture and improve tendon and enthesis healing. Ultimately, this work will establish the potential therapeutic role of HIF1a in tendon and enthesis repair following injury, improving clinical care for the prevention and treatment of common musculoskeletal injuries. For this work, we have developed a collaborative team across the University of Michigan that includes faculty in the Medical School (Orthopaedic Surgery: Adam Abraham, Noelle Whyte, and Matthew Stepanovich; Molecular and Integrative Physiology: Yatrik Shah and Jun Hee Lee) and the College of Engineering (Materials Science and Engineering: Claudia Loebel).

Karl Jepsen, Ph.D.

Associate Dean for Research

Glancy Family Scholar

Professor of Orthopaedic Surgery and Biomedical Engineering

Director, Michigan Integrative Musculoskeletal Health Center

Chair, Research and Academic Safety Committee

Congratulations Dr. Jepsen

R01 Award

Title: Giving a voice to a silent disease

 

Funding: $3.2M by NIH/NIAMS 

 

Narrative: The NIH grant will support work addressing the clinical conundrum regarding the inability of the current clinical diagnostic standards to accurately predict the risk of osteoporotic bone fractures related to aging and other conditions. To improve the accuracy of fracture risk prediction and move towards understanding the differences in individuals at risk, the research team will employ a novel approach that leverages previously hidden patterns of age-related bone structural changes arising from its complex adaptive nature and combines this with a unique intersection of AI/ML, probabilistic modeling, and uncertainty quantification. This approach is enabled by the combined strengths of a multi-institution research team and the leveraging of existing data collected longitudinally for men and women for nearly 2 decades. The research team includes UM investigators (Jepsen (coPI), Gregory Clines, MD, PhD, and Kayvan Najarian, PhD) and investigators at the University of Colorado, Colorado Springs (Bredbenner (coPI)), the University of California San Francisco (Peggy Cawthon, PhD), and the Oregon Health & Science University (Eric Orwoll, MD). Central to this effort is the expertise of co-PI Bredbenner who worked in the private contract research sector before moving into academics and has developed unique skills in probabilistic modeling and uncertainty quantification that will be used in combination with AI/ML to transform clinical diagnostics by predicting musculoskeletal tissue responses to known and unknown environmental factors.

 

The Vision: With the help of existing cohorts of individuals with longitudinally acquired data, we were able to show that the patterns of bone trait coordination that begin in growth carry over to the aging process. With aging, the narrow hip bone appears to continue to maximize its strength whereas the wide hip bone appears to minimize its mass. Thus, the early strength advantage of wide bones appears to be lost with aging and results in wide bones being at higher risk of fracturing with aging. Finding these patterns in aging bone allowed us to move away from treating populations as being homogeneous and to acknowledge the population heterogeneity by better understanding the diversity of structural changes and leveraging previously hidden patterns. Critically, the current clinical tools are not used in a way to recognize these patterns. Embracing this diversity prompted the hypothesis that a one-size-fits-all approach does not work for bone fragility and allowed us to test whether there are multiple mechanisms (trajectories) leading to increased fracture risk with aging. Because our biomarker, bone width, is established early in life, this research may enable us to move the diagnostic window decades earlier in life and to provide a voice to what has long been considered a silent disease. The bone structure speaks volumes, we just had to learn how to listen to it.

Congratulations Easton Farrell!

NIH F31 Predoctoral Award

On Friday, April 5, Easton Farrell, a third-year PhD student in Dr. Tristan Maerz's lab, received an F31 Ruth L. Kirschstein Predoctoral Individual National Research Service Award. This award enables promising predoctoral students with potential to develop into productive, independent research scientists, and will provide funding for the duration of Easton's thesis project. Following completion of his degree, Easton intends to complete a post-doc and later become a University lecturer. Congratulations to Easton!

Research Highlight

Andrea Alford, Ph.D.

Associate Research Scientist, Orthopaedic Surgery

Dr. Andrea Alford has been with the department since 2004.  She started as a post-doc with Dr. Kurt Hankenson. Her research focuses on interactions between osteoblast lineage cells and extracellular matrix in marrow and bone.

Research Interest: 

The Alford lab studies cell-extracellular matrix (ECM) interactions in bone. Bone tissue ECM is composed of mineral and type I collagen, which can be visualized using electron microscopy. In the images below, collagen fibrils were captured longitudinally (left panel) and in cross section (right panel). Both images were obtained using a sliver of mouse posterior femoral mid-diaphysis. Proper collagen structure and organization is required for bone’s resistance to fracture, and mutations in collagen or the proteins that facilitate its organization cause inherited and acquired bone fragility and fractures. The Alford lab studies the impacts of altered ECM on bone cell and ECM physiology.

G. Ying, Li, M.D., 

Frederick J. Fischer, M.D., Professor of Orthopaedic Surgery

Chief, Section of Pediatric Orthopaedic Surgery

G. Ying, Li, M.D., has been with the department since 2011. Dr. Li’s research focus is on pediatric spinal deformity and she has numerous publications on this topic.  She is a Principal Researcher and a member of the Research Council of the Pediatric Spine Study Group.  Dr. Li is an active member of the Pediatric Orthopaedic Society of North America and the Scoliosis Research Society, and has held leadership positions in both societies. 

Research Interest: 

The primary focus of Dr. Li’s research program is pediatric spinal deformity, including treatment outcomes of early onset scoliosis (EOS). Dr. Li is actively involved in numerous study groups and multicenter studies.  As a member of the Pediatric Spine Study Group (PSSG), an international organization that manages the largest registry of children with EOS, she has had the opportunity to participate in multicenter collaborative efforts, which is particularly important for rare conditions such as EOS.  Dr. Li has multiple publications using data from the PSSG registry, including a recent publication comparing parent- and patient-reported outcomes in EOS.  Current active projects include a study on outcomes of growth-friendly surgical treatment of EOS in children with prune belly syndrome and lowest instrumented vertebra selection in “tweener” patients with EOS treated with magnetically controlled growing rods vs posterior spinal fusion.

One of Dr. Li’s long-standing research interests in EOS is the evaluation of titanium levels in patients treated with growth-friendly instrumentation.  She received a grant from the Scoliosis Research Society in 2019 for a prospective study comparing serum titanium levels in EOS patients with growth-friendly instrumentation to age-matched controls, and evaluate serial serum and urine titanium levels in EOS patients.  This study was recently published in the Journal of Pediatric Orthopaedics.  She also received the Scoliosis Research Society-Cotrel Foundation Basic Science Award in 2022 for a study looking at the biological responses to titanium alloy debris using a pediatric animal model.  This project is a collaboration with basic science faculty in the Orthopaedic Research Laboratories at the University of Michigan.  Another related ongoing project with the ORL team is an analysis of magnetically controlled growing rod explants.

Dr. Li’s research also focuses on pediatric orthopaedic trauma and musculoskeletal infection.  She is a founding member of the Function after Adolescent Clavicle Trauma and Surgery (FACTS) study group and the Children’s Orthopaedic Trauma and Infection Consortium for Evidence Based Study (CORTICES).  Current active projects include a study on shared decision making and outcomes of nonoperative vs operative treatment of adolescent clavicle fractures based on racial, ethnic, socioeconomic, insurance, and sex-based differences, and development of a clinical prediction algorithm to differentiate between knee septic arthritis and Lyme arthritis in children.

Dr. Li holds leadership positions in several of these study groups and was elected by the PSSG to serve as Program Chair of the International Congress on Early Onset Scoliosis in 2025.

Welcome New Orthopaedic Research Faculty!

Rhima Coleman, Ph.D.

Associate Professor

Dr. Rhima Coleman's laboratory has moved from the School of Engineering LBME building to the Medical School BSRB. Dr. Coleman will join the faculty team in orthopeadic research. Her research is focused on investigation two key areas of manipulating cell behavior for cartilage tissue regeneration: 1) genetic reprogramming of cells and 2) cell-matrix interactions. Dr. Coleman will be presenting her research at Orthopaedic Surgery Research Day on May 15th. 

New Lab Equipment

We are pleased to announce that the Orthopaedic Surgery Research Service (OSRS) team has recently acquired new rapid prototyping equipment. This equipment is located in the Biomedical Research Science Building (BSRB).  In the coming weeks, we will be hosting a formal open house to showcase the capabilities of this equipment. We invite you to join us for a brief demonstration of the lab space and the new equipment. Your attendance and participation would be greatly appreciated

We extend our sincere appreciation to Conor Locke for his exceptional contributions to the research and acquisition process of our new equipment. His dedication and expertise have been instrumental in ensuring the successful implementation of this valuable addition to our facility.

Histology Core Highlight

Diversity, Equity, & Inclusion 

Health Care Equity Month

Michigan Medicine Healthcare Equity Month is intended to raise awareness, encourage action, and showcase Michigan Medicine- and U-M-led efforts around systemic health care inequities experienced by historically marginalized and underrepresented groups. You can watch the recorded session to learn more about Healthcare Equity Month

Past DEI Events:

https://pubmed.ncbi.nlm.nih.gov/32429740/

https://pubmed.ncbi.nlm.nih.gov/36401816/.

 

Are you interested in joining the DEI Committee (2-year service commitment)? If so, please send Megan Killian (mlkillia@med.umich.edu) an email.


Upcoming DEI Event:  

Orthopaedic Surgery will participate in the 2024 Youth Summit at the Big House on Saturday, May 18th! The Youth Summit at the Big House is an annual event where units across Michigan Medicine come together to host hundreds of local kids from underrepresented backgrounds in order to get them interested and knowledgeable about careers in healthcare. 

Staff Celebrations! 

Employee Engagement Survey Celebration!

The staff commemorated their accomplishment of achieving a 100% participation rate in completing the Employee Engagement Survey with a catered event from Jerusalem Garden. This celebration not only recognizes the collective effort of the team but also underscores the importance placed on employee engagement and feedback within the organization. Such initiatives contribute significantly to fostering a culture of collaboration and continuous improvement. Great job, Orthopaedic Surgery Research Service (OSRS) team!

Research Resource Spotlight

Freezerworks:

Freezerworks is a software that is licensed by Michigan Medicine to support your work. This software allows you to set your freezer in a virtual environment and track samples, aliquots (or tissue sections), and other sample status/data. It takes a while (and a Freezerworks rep) to set up the program, so allow a couple of months and a couple of hours of meetings from start to finish. However, once you are done, it will be easy to keep track of complex biorepository projects, freezer space availability, and many other sample metrics, enter data, and generate routine reports at the click of a button. Start by visiting https://software.umich.edu/titles/freezerworks and submit a ticket for a consultation with the HITS team. 

Recent Publications

Upcoming Funding Opportunities and Deadlines


Meaningful May

"Meaningful May" sounds like a wonderful theme! It's always important to take the time to show appreciation for those we care about and to work towards our goals. I encourage you to complete at least 2 of these actions this May

“Think of all the beauty still left around you and be happy.” —Anne Frank

Administrative Team

Melissa Li

Research Manager

for research operations

Kaileigh Stuchlik

Research Admin Manager

for research administration

Andrea Rusnak

Clinical Research Project Manager 

for clinical research

Sarah Boston

Admin Assistant Specialist 

for admin support