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Picture of Dominik R Haudenschild

 

Dominik Haudenschild

Associate Professor
drhaudenschild@ucdavis.edu
Lab.Haudenschild.org

Orthopedics (School of Medicine)
Orthopaedic Surgery - Medicine
Molecular & Cellular Biology
Biomedical Engineering (Grad)

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



Degrees:

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

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.
http://www.ucdmc.ucdavis.edu/orthopaedics/ourteam/biodetail.asp?bioid=1339

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.
http://www.ucdmc.ucdavis.edu/orthopaedics/ourteam/biodetail.asp?bioid=1339

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

Professional Societies:

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

CBS Graduate 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:

Last updated 8/1/2014
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
 


Laboratory Personnel:

Haudenschild
http://lab.haudenschild.org
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 2013 Fall, 2014 Winter
Seminar BIM298D Seminar Based Discussion of Current Topics in Orthopaedic Research Spring 2013

Key Words:

Cartilage, Chondrocyte, Mechanotransduction, Cartilage Injury, Osteoarthritis, Cytoskeleton, Actin and Vimentin, Chondrogenesis, Biomarker, COMP,