News & Events
In this paper, we used optogenetics as a noninvasive tool for direct and precise induction of muscle contraction for in vivo tendon loading in growing mice.
Recent optogenetics publication in Science Advances
Our recent paper using optogenetics to control tendon and enthesis loading has been published in Science Advances ! This work was led by Elahe Ganji, PhD, and Syeda Lamia.
Abstract: Skeletal shape depends on the transmission of contractile muscle forces from tendon to bone across the enthesis. Loss of muscle loading impairs enthesis development, yet little is known if and how the postnatal enthesis adapts to increased loading. Here, we studied adaptations in enthesis structure and function in response to increased loading, using optogenetically induced muscle contraction in young (i.e., growth) and adult (i.e., mature) mice. Daily bouts of unilateral optogenetic loading in young mice led to radial calcaneal expansion and warping. This also led to a weaker enthesis with increased collagen damage in young tendon and enthisis, with little change in adult mice. We then used RNA sequencing to identify the pathways associated with increased mechanical loading during growth. In tendon, we found enrichment of glycolysis, focal adhesion, and cell-matrix interactions. In bone, we found enrichment of inflammation and cell cycle. Together, we demonstrate the utility of optogenetic-induced muscle contraction to elicit in vivo adaptation of the enthesis.
This work was supported by funding from the NSF CAREER and NIH R01 (NIAMS) and R03 (NICHD).
Syeda presented her research as a podium talk at the SB3C2023.
Syeda presented her dissertation work at the SB3C conference in the PhD level student paper competition in Vail.
In June, Syeda competed as one of 36 finalists in the PhD level student paper competition at the SB3C meeting in Vail. There were >200 abstracts submitted to the competition this year. Syeda also helped organize a meetup for BUET alumni at the SB3C meeting and went on several hikes in the Rockies.
MiMHC Symposium 2023 recap + Steph wins a travel award!
This year's MiMHC Symposium was a hit, with excellent scientific presentations and high caliber posters.
Our laboratory presented five posters, including:
-Brandon's study assessing bone morphometry of a mouse model for gender-affirming hormone therapy
-Syeda's study assessing skeletal muscle contractility using e-stim and optogenetics of mouse muscle with and without eYFP
-Steph's *award winning* poster (and first-ever podium talk!) on her study of extracellular matrix associated gene expression in tendon fibroblasts and its dependence on Hif1a. Steph won a MiMHC travel award!
-LeeAnn's study investigating the role of AMPKa1 on tendon homeostasis and matrix remodeling in vivo.
-LeeAnn's study (presented by Dr. Abraham) on tendon cell-matrix interactions (not pictured).
LeeAnn presents her dissertation work at the APS Summit in Long Beach!
LeeAnn (Hold) Flowers presented her dissertation work as a poster ("AMPKα1 is necessary for extracellular matrix homeostasis in mouse Achilles tendon") at the APS Summit in Long Beach this April. Her abstract was selected as an Abstract of Distinction ! Congratulations, LeeAnn!
The growth and adaptation of the enthesis depends on FGF signaling. In these two studies, we used transgenic mouse models to interrogate the role of FGF ligand (FGF9) and receptors (FGFR1 and FGFR2) in Scx-lineage cells during postnatal growth. Schematic created with BioRender.com.
Two papers related to our FGF signaling work have been recently accepted in Developmental Dynamics and The FASEB J
Two publications from our FGF signaling projects were recently accepted for publication in the journals Developmental Dynamics and The FASEB Journal. These include:
"Loss of Fgfr1 and Fgfr2 in Scleraxis-lineage cells leads to enlarged bone eminences and attachment cell death," led by Killian lab alumni Kendra Wernle and Michael Sonnenfelt with Connor Leek, Elahe Ganji, Anna Lia Sullivan, and our collaborators at WashU, and "Targeted deletion of Fgf9 in tendon disrupts mineralization of the developing enthesis," led by Elahe Ganji with Connor Leek and our WashU collaborators, Drs. David Ornitz and Deb Patra.
Syeda presented her research as a poster at the ORS2022.
The enthesis is a transitionally graded tissue positioned between bone and tendon. The primordial enthesis develops from bi-fated progenitor cells expressing chondrogenic and tenogenic factors (i.e., Scx, Sox9, and Gli1). Created with BioRender.com.
Review published in Seminars in Cell and Developmental Biology
Our recent review paper, "Growth and mechanobiology of the tendon-bone enthesis," is now published as part of the Special Issue on Musculoskeletal Physiology, edited by Dr. Ryan Riddle. This manuscript highlights much of our current understanding of enthesis research, and highlights some new directions towards which the field is headed.
Abstract: Tendons are cable-like connective tissues that transfer both active and passive forces generated by skeletal muscle to bone. In the mature skeleton, the tendon-bone enthesis is an interfacial zone of transitional tissue located between two mechanically dissimilar tissues: compliant, fibrous tendon to rigid, dense mineralized bone. In this review, we focus on emerging areas in enthesis development related to its structure, function, and mechanobiology, as well as highlight established and emerging signaling pathways and physiological processes that influence the formation and adaptation of this important transitional tissue.
Schematic of biomaterial design for musculoskeletal regeneration, from HarleyLab.org
NIH NIAMS R01 subcontract with Dr. Brendan Harley at University of Illinois awarded!
We recently received R01 funding from the NIAMS (PI: Brendan Harley at the University of Illinois-Urbana Champaign) to translate spatially-graded biomaterials for improving enthesis regeneration in vivo! This five-year programmatic grant is an extension of an R56 that Dr. Harley received in 2020. We are excited to continue this collaborative work with folks here at Michigan Medicine (including Dr. James Carpenter) and at UIUC (including Dr. Simon Rogers). Also, this is our first multi-uni B1G funding!
The organization of the growth plate of long bones (left) resembles that of the tendon-bone interface (right).
NIH NIAMS R01 funded!
Dr. Killian is the PI on a recently awarded R01 titled: FGF signaling during growth and mechanical adaptation of tendon-bone interfaces. This project includes collaborations with Dr. David Ornitz (WUSTL) and Drs. Ken Kozloff, Sue Brooks, and Kurt Hankenson (University of Michigan).
Congratulations, Dr. Leek!
Connor Leek successfully defended his PhD work on The Role of Fibroblast Growth Factor Signaling During Superstructure Development and in Muscle-Bone Crosstalk. Read more here
Elahe awarded the Beckman Postdoctoral Fellowship!
PhD student, Elahe Ganji, was awarded the Beckman Postdoctoral Fellowship, which will support 3 years of postdoctoral training at the University of Illinois with Drs. Mariana Kersh and Kate Clancy.
Review in TMIR published!
PhD student, Connor Leek, and undergraduate students, Jaclyn Soulas and Anna Lia Sullivan, each contributed equally to a recent review entitled: Using Tools in Mechanobiology to Repair Tendons, which was published in a special issue (Cell Behavior Manipulation) in the new open-access journal, Current Tissue Microenvironment Reports.
Elahe Ganji awarded the University Doctoral Fellowship
Congratulations to Elahe Ganji, a fourth year PhD student in Mechanical Engineering (University of Delaware) on being selected for the University Doctoral Fellowship Award from the University of Delaware! This award will support Elahe for her doctoral research over the next academic year and is a competitive award. Elahe was one of two students nominated from her home department.
Professor Killian receives the prestigious NSF CAREER Award
In this CAREER project, Professor Killian will use an in vivo optogenetic platform to measure structural, mechanical, and molecular changes induced by remodeling and damage of the tendon attachment that are driven by frequency-, magnitude-, and duration-dependent changes in muscle loading, both during postnatal growth and in the mature and aging attachment.
Killian Lab at #ORS2020
The Killian Lab had a record attendance at this year's Orthopaedic Research Society Annual meeting in Phoenix, where three undergraduate and three graduate students presented their orthopaedic research.