Dominik Haudenschild

image of Dominik Haudenschild

Associate Professor

Departments

Orthopaedic Surgery - Medicine
Biomedical Engineering (Grad)
Orthopedics (School of Medicine)

Offices and Labs

Research I/UCDMC Sacramento, CA 95817
+1 916 734 5015
+1 530 746 8866

Degrees

2003 Ph.D. Biochemistry Molecular Biology UC Davis
1989 BA Biology Boston University

Research Interests

Osteoarthritis Animal Model and Biomarkers

Osteoarthritis is a painful and debilitating disease that results in loss of joint function. Because cartilage is an aneural and avascular tissue, patients often do not seek medical advice until there is irreversible loss of cartilage. At that stage, painful bone-bone contact occurs in the joints. Knee and hip osteoarthritis is often the end-stage result of silent pain-free chronic cartilage degradation that occurs over years or even decades. A portion of my lab is dedicated to identifying serum biomarkers of this pre-arthritic cartilage degradation. The goal is to create a screen which can be routinely used by physicians to identify patients at risk for joint failure due to osteoarthritis, in a similar fashion as serum cholesterol levels are currently used to identify patients with silent cardiovascular disease that are at risk for heart failure or stroke. Minor joint injuries, such as an ACL or meniscus tear, ultimately lead to arthritis in most cases. The damage that initiates arthritis begins almost immediately at the cellular level. Despite this, current clinical care of ACL tears does not address the initial damage that leads to future arthritis. We have developed a non-surgical mouse model of ACL tears, in which we study the cellular responses to this type of injury, with the goal of developing intervention strategy at the time of injury to prevent future arthritis.

Chondrocyte Mechanotransduction

Most people understand that lifting weights will increase muscle mass, loss of activity causes unused muscles to shrink, and too much activity can lead to injury. It turns out that the same is true for cartilage: moderate mechanical loads are required for cartilage homeostasis. Too little, or excessive loading causes cartilage matrix to be lost or damaged. Mechanotransduction is the process through which cells within cartilage sense the mechanical forces and convert them to biochemical signals. A portion of my lab studies mechanotransduction, the interactions between the chondrocyte cytoskeleton and signal transduction events which lead to the regulation of gene expression and extracellular matrix synthesis that is required for the maintenance of health cartilage.

Growth Factor-Matrix Interactions

Our recent discovery is that Cartilage Oligomeric Matrix Protein (COMP) is a multivalent TGF-beta binding protein, and that COMP-bound TGF-beta has more activity than free unbound TGF-beta. We are exploring the ability of COMP to augment TGF-beta activity in cartilage and bone tissue engineering applications, and mapping the binding exact binding site to get a better understanding of the mechanisms involved.

Awards

Arthritis Foundation
Department of Defense
NIH NIAMS R03
NIH NIAMS R21

ProfessionalSocieties

Orthopaedic Research Society
International Cartilage Repair Society
OsteoArthritis Research Society International
American Society for Bone and Mineral Research

CBS Grad Group Affiliations

Biochemistry, Molecular, Cellular and Developmental Biology

Specialties / Focus

Biochemistry, Molecular, Cellular and Developmental Biology
  • Signal Transduction and Gene Regulation

Graduate Groups not Housed in CBS

Biomedical Engineering Graduate Group

Publications

10/10/2014 8:18:21 AM
  • 2014 "In Vivo Fluorescence Reflectance Imaging of Protease Activity in a Mouse Model of Post-Traumatic Osteoarthritis." Osteoarthritis & Cartilage
  • 2014 "Cartilage Oligomeric Matrix Protein and its Binding Partners in the Cartilage Extracellular Matrix: Interaction, Regulation and Role in Chondrogenesis." Matrix Biol 2014.
  • 2014 "Cyclin-Dependent Kinase 9 inhibition protects cartilage from the catabolic effects of pro-inflammatory cytokines." Arthritis Rheumatol.
  • 2014 "Comparison of loading rate-dependent injury modes in a murine model of post-traumatic osteoarthritis." Journal of Orthopaedic Research
  • 2014 "The Effect of Noggin Interference in a Rabbit Posterolateral Spinal Fusion Model." European Spine Journal
  • 2013 "The oncogene leukemia/lymphoma-related factor (LRF) stimulates proliferation of mesenchymal stem cells and inhibits their chondrogenic differentiation." Cartilage, 4(4): 329-338.
  • 2013 "Effect of age and cytoskeletal elements on the indentation-dependent mechanical stiffness of chondrocytes." PLoS ONE
  • 2013 "Cartilage Oligomeric Matrix Protein Enhances Osteogenesis by Directly Binding and Activating Bone Morphogenetic Protein-2." Bone
  • 2013 "Interactions Between FGF21 and BMP-2 in Osteogenesis." Biochemical and Biophysical Research Communications
  • 2013 "c-Maf Transcription Factor Regulates ADAMTS-12 Expression in Human Chondrocytes." Cartilage
  • 2012 Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis." Osteoarthritis & Cartilage, PMID: 22531459.
  • 2012 "Identification of a 3Kbp Mechanoresponsive Promoter Region in the Human Cartilage Oligomeric Matrix Protein Gene." Tissue Engineering Part A, PMID:22764748.
  • 2012 "The Oncogene LRF is a Survival Factor in Chondrosarcoma and Contributes to Tumor Malignancy and Drug Resistance." Carcinogenesis. PMID:22847180
  • 2012 "Chondrogenic Potential and Homogeneity of Cell Populations of Donor and Recipient Cells in a Fresh Osteochondral Allograft: A Case Report." Haudenschild DR, Hong E, Hatcher SL, and A.A. Jamali. Journal of Bone and Joint Surgery
  • 2011 "Enhanced Activity of TGF-ß1 Bound to Cartilage Oligomeric Matrix Protein." Li H, Haudenschild DR, Di Cesare PE, Posey K, Hecht J, and Yik JHN. Journal of Biological Chemistry
  • 2011 "Comparative Analysis with Collagen Type II Distinguioshes Cartilage Oligomeric Matrix Protein as a Primary TGF-ß-Responsive Gene." Osteoarthritis Cartilage.
  • 2011 "Vimentin contributes to changes in chondrocyte stiffness in osteoarthritis." Haudenschild DR, Chen J, Pang N, Steklov N, Grogan SP, Lotz MK, D'Lima DD. Journal of Orthopaedic Research
  • 2011 "Role of c-Maf in Chondrocyte Differentiation: A Review." Eunmee Hong, Paul E. Di Cesare, and Dominik R. Haudenschild. Cartilage
  • 2010 "Rho Kinase-Dependent Activation of SOX9 in Chondrocytes", Arthritis & Rheumatism
  • 2009 "Characterization of the Chondrocyte Actin Cytoskeleton in Living Three-Dimensional Culture: Response to Anabolic and Catabolic Stimuli" Molecular Cellular Biomechanics
  • 2008 Rho Kinase-Dependent CCL20 Induced by Dynamic Compression of Human Chondrocytes." Arthritis & Rheumatism
  • 2008 "Dynamic Compression of Chondrocytes Induces a Rho Kinase-Dependent Reorganization of the Actin Cytoskeleton." Biorheology.
  • 2008 "Immunolocalization of IL-17A, IL-17B, and Their Receptors in Chondrocytes During Fracture Healing" Journal of Histochemistry & Cytochemistry
  • 2006 "Interleukin-17 Receptor-Like Gene is a Novel Anti-apoptotic Gene Highly Expressed in Androgen-Independent Prostate Cancer" Cancer Research
  • 2006 "Generation of Interleukin-17 Receptor-Like Protein (IL-17RL) in Prostate by Alternative Splicing of RNA" The Prostate
  • 2006 "Bone Morphogenetic PRotein (BMP)-6 Signaling and BMP Antagonist Noggin in Prostate Cancer". Cancer Research
  • 2003 "Interleukin-17 Family and IL-17 Receptors." Cytokine & Growth Factor Reviews
  • 2002 "Soluble and Transmembrane Isoforms of Novel Interleukin-17 Receptor-like Protein by RNA splicing and Expression in Prostate Cancer". Journal of Biological Chemistry
  • 2001 "Differential Expression of Multiple Genes During Articular Chondrocyte Redifferentiation". Anatomical Record
  • 2000 "BMP Family" Review
  • 1998 "Expression of a Stable Articular Cartilage Phenotype without Evidence of Hypertrophy by Adult Human Articular Chondrocytes in Vitro." Journal of Orthopaedic Research
  • 1996 Cartilage Matrix Protein: Expression Patterns in Chicken, Mouse, and Human." Annals New York Academy of Sciences
  • 1995 The Role of Coiled-Coil alpha-Helices and Disulfide Bonds in the Assembly and Stabilization of Cartilage Matrix Protein Subunits: A mutational Analysis." Journal of Biological Chemistry
  • 1995 "Progression and Recapitulation of the Chondrocyte Differentiation Program: Cartilage Matrix Protein is a Marker for Cartilage Maturation." Developmental Biology
  • 1995 "Cartilage Matrix Protein Forms a Type II Collagen-independent Filamentous Network: Analysis in Primary Cell Cultures with a Retrovirus Expression System." Molecular Biology of the Cell
  • 1994 "Link Protein is Ubiquitously Expressed in Non-cartilagenous Tissues Where it Enhances and Stabilizes the Interaction of Proteoglycans with Hyaluronic Acid." Journal of Biological Chemistry

Labs

Haudenschild website
  • Dominik Haudenschild PI; Jasper Yik, Ph.D. - Project Scientist; Tomoaki Fukui, MD, Ph.D., - Post-doctoral Fellow; Adam Wegner - MD, Ph.D., - Research Resident; Jeffrey Lu - Ph.D. Candidate BMEGG; Michael Fong - Ph.D. Student BMEGG; Michael Robbins - Medical Student Yasaman (Jasmin) Arabi - UC Davis Undergraduate volunteer; Maneesh Vij, Yale Undergraduate Intern Previous Lab Members 2014 Elizabeth Tenborg - Research Specialist, Attending Veterinary School; 2014 Nina Liu - Undergraduate volunteer; 2014 Kie Shidara - Undergraduate volunteer; 2013 Kazunari Ishida, M.D., Ph.D. - Post-doctoral Fellow, took position as practicing clinician at Kobe University in Japan; 2013 Ethan Hu, M.D., Ph.D., - Post-doctoral Fellow; 2012 Chitrangada Acharya Post-doctoral fellow, now at Allied Innovative Systems; 2011 Eunmee Hong, Post-doctoral fellow, Joined Orthopaedic Research Lab as post-doctoral fellow for Dr. Hari Reddi; 2010 Kaylene Snow Junior Specialist; 2009 Derek Amanatullah Orthopaedic Surgery Fellow, Finishing Residency Training, Accepted Fellowship at Mayo Clinic; 2013 Ashlene Kishore - Undergraduate Volunteer - applying to medical school; 2012 Victoria Van Dinh Undergraduate Volunteer, applying to medical school; 2012 Edward Yeh - UCD Undergraduate Volunteer - finishing degree; 2012 Lawrence Lin UCD Undergraduate Volunteer - finishing degree; 2012 Joanna Turkiewicz - UCD Undergraduate Volunteer - finishing degree;

Field Sites

UC Davis Medical Center

Courses

Rotations MCB 220L MCB Rotation Course (2014 Fall, 2015 Winter)
Seminar BIM298D Seminar Based Discussion of Current Topics in Orthopaedic Research (Spring 2015)