Musculoskeletal Research Training Program (T32)

Our Goals:

• Train predoctoral students and postdoctoral fellows for research careers as basic scientists or clinical investigators studying the causes and treatments of musculoskeletal diseases

• Develop an educational environment for students and postdoctoral fellows which encompasses a modern spectrum of research in musculoskeletal diseases, including basic discovery, investigation of musculoskeletal disease models, and study of outcomes of standard treatments

These primary focus groups allow for and encourage cross-disciplinary interactions between molecular biologists, (stem) cell biologists, orthopedic surgeons, veterinary researchers, and bioengineers. The primary interests of each faculty member guide placement into the groups; however, many faculty members make significant contributions to more than one focus group.

Musculoskeletal Cancer Biology and Therapeutics
(D.R. Clohisy,* M. Garwood, D. Largaespada, J. Modiano)

The collective focus of this group is to understand the etiology, progression, and clinical sequelae of musculoskeletal cancers and to develop new therapies for treatment and prevention. Specific areas of this research include:

• Cellular mechanisms regulating osteolysis in cancer
• Bone cancer-associated pain and tumor metastasis to bone 
• Animal models of sarcoma
• Clinical epidemiology research in osteosarcoma and rhabdomyosarcoma
• Development of new techniques in MR imaging and oncology 

Osteoarthritis and Cartilage Biology Group
(C. Carlson,* J. Bechtold, P. Ludewig, G.E. Pluhar)

This group has a common interest in understanding the etiology and treatments of osteoarthritis. Specific areas of research include:

• Development and validation of animal models of osteoarthritis
• Bone fracture repair
• Biomechanics of the shoulder joint
• Pathophysiology of degenerative osteoarthritis of the spine

Musculoskeletal Development Group
(R. Gopalakrishnan, D. Kaufman, K. Mansky, L. Potter, M. O'Connor)

This group is unified by the common interest of understanding the molecular mechanisms that regulate skeletal development, maturation, and differentiation. Specific areas of research include:

• Osteoblast and osteoclast biology and the role of these cells in the physiologic and pathophysiologic formation of the skeleton
• Mechanisms involved in limb regeneration in xenopus tadpoles
• Skeletal aberrations occurring in dwarfism
• Estrogen signal transduction cascades in bone metabolism and cancer biology

Epidemiology and Clinical Outcomes Research Group
(L. Spector*, M. Swiontkowski)

This group of investigators applies state-of-the-art epidemiologic and clinical outcomes research methodologies to critically evaluate a wide variety of musculoskeletal treatments. This group has multiple strengths but the two most important are their access to large patient/sample populations through cooperative multi-institutional trials and their international reputation in orthopedic-based clinical outcomes research. Specific areas of research include:

• Assessment of functional outcomes for the treatment of musculoskeletal conditions
• Etiology and behavior of musculoskeletal cancers

Director:

Denis R. Clohisy, MD

Co-Directors:

Cathy Carlson, DVM, PhD and Kim C. Mansky, PhD

Advisory Council:

• Paula Ludewig, PhD
• Lincoln Potter, PhD
• Logan Spector, PhD

Faculty:

• Victor Barocas, PhD
• Joan Bechtold, PhD
• Bryce Binstadt, MD, PhD
• Michael Garwood, PhD
• Raj Gopalakrishnan, DDS, PhD
• Eric Jensen, PhD
• Yasuhiko Kawakami, PhD
• David Largaespada, PhD
• Dawn Lowe, PhD
• Jaime Modiano, VMD, PhD
• Branden S. Moriarity, PhD
• G. Elizabeth Pluhar, PhD
• Lincoln Potter, PhD
• Subree Subramanian, PhD
• Troy Trumble, DVM, PhD

Predoctoral

• Laura Antos, PhD

• Characterizing ATP’s effect on natriuretic peptide receptors in relation to long bone growth using fibroblast cell cultures

• Mentor: Lincoln Potter, PhD
  

• Emily Bermel

• Developing a theoretical/computational model of the degeneration process using growth and remodeling theories in conjunction with realistic models of the tissue geometry and properties

• Mentor: Victor Barocas, PhD

• Charles Billington, PhD

• Examining the spectrum of craniofacial malformations resulting from a mutation of the gene Twisted Gastrulation

• Mentor: Anna Petryk, MD

• Nicholas Blixt 

• Providing mechanistic insight into controlling osteoclast differentiation as a potential new therapy for osteoporosis or other diseases characterized by uncontrolled bone loss

• Mentor: Kim Manksy, PhD

• Christina Brakken-Thal, PhD

• Understanding how Decapentapolegic (Dpp), a BMP protein, is regulated to pattern the dorsal surface of the embryo

• Mentor: Michael O’Connor, PhD

• Aaron Broege, PhD

• Determining how delta EF1 regulates osteoblast development 

• Mentor: Michael Sanders, PhD

• Amy Claeson, PhD

• Developing a multi-scale understanding of the structure and mechanical properties of the lumbar facet capsular ligament (FCL) at the spinal, segmental, and tissue levels

• Mentor: Victor Barocas, PhD

• Brandon Diessner, PhD

• Identifying genetic variants that predispose individuals to osteosarcoma and Ewing sarcoma development

• Mentor: Logan G. Spector, PhD

• Aaron Edmund, PhD

• Discovering the mechanisms of activation and inactivation of natriuretic peptide receptors

• Mentor: Lincoln Potter, PhD

• Arin Ellingson, PhD 

• Measuring the helical axis of motion of lumbar spinal motion segments using a human cadaveric model to establish factors that are distinguishable and correlated by the location and/or direction of the helical axis throughout motion

• Mentor: David Nuckley, PhD

• Bora Faulkner, PhD

• Understanding the mechanism by which histone deacetylase 4 ( HDAC4 ) regulates osteoclasts gene expression and differentiation.

• Mentor: Kim Mansky, PhD

• Sarah Frommer, PhD 

• Investigating the use of stem cells as treatment for Duchenne Muscular Dystrophy.

• Mentor: Catherine Verfaillie, MD

• Liz Gacek, PhD

• Mechanically characterizing and computationally modeling the lumbar facet capsular ligament (FCL)

• Mentor: Victor Barocas, PhD

• Craig Kage

• Cervical spine kinematics

• Mentor: Arin Ellingson, PhD

• Rachel Kahler, PhD 

• Defining the intentions of the transcription factors, Runx2 and LEF1, and determining the role of LEF1 in osteoblast differentiation.

• Mentor: Jennifer Westendorf, PhD

• Rebekah Lawrence, PT, DPT, OCS

• Developing a biomechanical model based on kinematic data that will help establish a foundation for a clinical examination of movement impairments for people with shoulder pain

• Mentor: Paula Ludewig, PhD, PT

• Margaret McNulty, PhD 

• Developing a histological grading scheme for osteoarthritis in mice.

• Mentor: Cathy Carlson, DVM, PhD

• Branden Moriarity, PhD 

• Identify osteosarcoma (OS) development and metastasis genes by using candidate genes from a forward genetic screen

• Mentor: David Largaespada, PhD

• Christopher Peters, PhD 

• Identifying unique cellular interactions that occur within the bone microenvironment in both osteolytic and osteoblastic models of bone cancer

• Mentor: Patrick Mantyh, PhD, JD

• Emily Pope, PhD

• Characterizing adaptations in the extracellular matrix (ECM) remodeling and tumor microenvironment in response to chemotherapy

• Mentor: David Largaespada, PhD

• Jerid Robinson, PhD 

• The natriuretic peptide receptor B (NPR-B), which has relevance in musculoskeletal research via its effects on long bone growth.

• Mentor: Lincoln Potter, PhD

• Gaura Saini, DPT

• Testing how anticipated patterns of muscle activation based on movement patterns identified using biplane fluoroscopy correlate to quantitatively observed muscle activity

• Mentor: Paula Ludewig, PhD, PT

• Brandon Smeester

• Validating candidate cancer genes using the CRISPR system and testing novel therapeutic targets to treat osteosarcoma

• Mentors: Branden Moriarty, PhD and David Largaespada, PhD 

Postdoctoral

• Alexandra Armstrong, DVM

• Osteochondrosis (OC)/juvenile osteochondritis dissecans (JOCD)

• Mentor: Cathy Carlson, DVM, PhD, DACVP

• Randy Daughters, PhD 

• Understanding the origin and specification of satellite cells during embryonic development and their contribution to muscle regeneration in Xenopus Laevis tadpole tails

• Mentor: Jonathan Slack, PhD

• Dawne Dougherty, PhD 

• Understanding prostate cancer as it progresses to bone metastases, particularly with respect to the contributing hormonal signaling pathways

• Mentor: Michel Sanders, PhD

• Emily Gillespie, MD 

• Discovering underlying systemic autoimmune disease with the hope of improving disease management and generating better therapies

• Mentor: Timothy Behrens, MD

• Curtis Goreham-Voss, PhD 

• Applying finite element analysis to simulate the implant-bone fixation

• Mentor: Joan Bechtold, PhD

• Eric Jensen, PhD 

• Studying interactions between Runx2 and histone deacetylases in the regulation of bone-specific genes.

• Mentor: Jennifer Westendorf, PhD

• Kristina Kiefer, DVM 

• Evaluating the use of canine adipose derived stem cells as a therapeutic modality for the treatment of intervertebral disc disease and degenerative myelopathy, as well as other various orthopedic conditions in canines

• Mentor: Elizabeth Pluhar, DVM, PhD

• Gengyun (Coco) Le, PhD

• Investigating how estrogen affects the inflammatory responses and strength recovery following traumatic muscle injury

• Mentor: Dawn Loe, PhD

• Amanda Leightner, PhD

• Understanding the role of PKD2 in osteoclast differentiation and function 

• Mentor: Eric Jensen, PhD

• Carol Lin, MD 

• Comparing reoperation rates and outcomes in patients not enrolled or excluded from SPRINT to assess the influence of enrollment in the trial

• Mentor: Marc Swiontkowski, MD

• John Looft, PhD

• Developing a high fidelity shoulder finite element model for clinical applications by combining finite element models along with MRI and fluoroscopy to develop predictive models for diagnosing shoulder pain and dysfunction

• Mentor: Paula Ludewig, PhD

• Kai Ludwig, PhD

• Developing and evaluating advanced magnetic resonance imaging (MRI) techniques at clinical-strength and ultra-high magnetic field for noninvasive diagnosis and monitoring of musculoskeletal diseases (e.g., juvenile osteochondritis dissecans (JOCD)

• Mentors: Jutta Ellermann MD, PhD, and Greg Metzger, PhD

• Shawn Mahmud, MD, PhD

• Understanding the breakdown of tolerance in human autoimmune diseases by identifying, tracking, and characterizing rare, autoreactive T and B cells to understand how they cause autoimmunity

• Mentors: Marc Jenkins, PhD, and Bryce Binstadt, MD, PhD

• Christiana Raymond-Pope, PhD

• Examining the musculoskeletal system following complex orthopedic and volumetric muscle loss (VML) injury

• Mentor: Sarah M. Greising, PhD