Viscoelastic Properties of Normal and OA Chondrons
R01 AG015768 (Guilak)
The goal of this study is to determine the mechanical properties of the pericellular matrix of articular chondrocytes using micropipette aspiration and microindentation techniques.
Designer Stem Cells for Treating Chronic Diseases
The Nancy Taylor Foundation (Guilak)
09/01/2013 – 01/31/2020
The goal of this project is to create a unique, customized cell type that can sense and respond to its biochemical environment in a pre-programmed way to provide long-term therapy for chronic diseases.
Obesity, Biomechanics, and Inflammation in Osteoarthritis
R01 AG046927 (Guilak)
The goal of this project is to examine the influence of dietary fatty acids on obesity-associated OA in mice, and to examine their interaction with altered biomechanical and pro-inflammatory cytokines using various in vivo and in vitro models.
Engineering New Biological Therapies for Arthritis
Arthritis Foundation $92,593
The goal of this study is to expand the scope of ongoing research by incorporating cutting edge techniques in gene therapy and genome editing.
Intra-Articular Delivery of Sustained Release NF-kB Antagonists in Arthritis
R01 AR070975 (PI: Setton)
02/01/2017 – 01/31/2022
This study will develop a safe, sustained-release drug depot from silk, formulated specifically for small molecule antagonists of inflammation to be injected into the joint space. This work will establish a new strategy for the treatment of osteoarthritis that has potential to improve clinical utility for an entire class of inexpensive small molecule drugs that has a high likelihood of treating pathology or pain development in patients affected by osteoarthritis.
Muscle Stem Cells reprogrammed Through Genome Engineering for Autonomously Regulated Anti-Fibrotic Therapy
R21 AR072870 (PI: Huard)
Steadman Philippon Research Institute via NIH Prime $49,196
The long term goal of the application is to demonstrate that genome engineering facilitated the rewiring of endogenous cell circuits in order to define prescribed input/output relationships between fibrotic mediators (TGF-1) and their antagonists (decorin), potentially providing a cell-based drug delivery via a rapidly responding, auto-regulated system. The customization of intrinsic cellular signaling pathways in therapeutic stem cell populations will open innovative possibilities for safer and more effective treatments applicable to a wide variety of muscle diseases and injuries.
Regulation of Chondrogenesis by Long Non-Coding RNAs
R21 AR072193 (McAlinden)
The goals of this study are to determine the function and mechanism of specific human long non-coding RNAs (lncRNAs) in regulating chondrocyte differentiation and cartilage formation. LncRNAs are transcripts of greater than 200 nucleotides with no protein coding potential that can function to regulate gene expression or protein function to coordinate cellular processes critical for tissue-specific differentiation. While there is compelling data on the role of lncRNAs in other systems, there is a significant gap in our understanding of how lncRNAs function in cartilage biology.
WU Rheumatic Diseases Resource-based Center
P30 AR073752 (Pham/Lenschow)
US NIH Salary Support Only
The overarching goal of the Washington University Rheumatic Diseases Research Reource-based Center (WU_RDRRC) is to advance research in rheumatic diseases by providing the infrastructure, resources and opportunities for multiple levels of inquiry and translating those discoveries into treatments for delivery to patients
Role: Genome Engineering Core Director
Resource Based Center for Musculoskeletal Biology and Medicine
P30 AR074992 (Silva)
We will provide essential support for our Research Community to develop, implement and evaluate animal models for musculoskeletal biology and medicine, while fostering development of the next generation of musculoskeletal investigators. Our goal is to advance current knowledge to bridge gaps in our understanding of the cellular, molecular and functional basis of joint arthritis, and to develop and evaluate new therapeutic strategies.
Engineering Smart Cells for Arthritis Therapy
We propose to apply an innovative combination of principles from synthetic biology and genome engineering to create “smart” cells containing defined computational gene circuits that can sense and respond to their environment in a pre-programmed way.
Epigenetic Regulation of Chondrogenesis and Cartilage Development
K99 AR075899 (Wu)
The long-term goal of our proposed work is to unravel novel epigenetic mechanisms governing chondrocyte specification and cartilage development at the cellular and molecular levels.
Cellular and Molecular Mechanisms of Murine Digit Regeneration
F32 AR074895 (Qu)
NIH NIAMS $63,926
The objective of this project is to determine the spatiotemporal contribution and mechanism of activation of osteoblast lineage cells from the periosteum during murine digit regeneration.
Piezo Channel Activation and Mechanotransduction in Chondrocytes
F32 AR074240 (Nims)
NIH NIAMS $63,310
The objective of this project is to characterize the mechanical activation of Piezo channels at the cellular and tissue level and the subsequent gene regulation initiated by Piezo activation. This work will develop a fundamental understanding of Piezo channels in chondrocyte mechanotransduction and the consequences of Piezo activation on gene expression for developing therapies to treat or prevent posttraumatic osteoarthritis.