Medical Student Research Fellowship for Summer 2009
Mentor: Dr. Lawson A. B. Copley.
Department: Pediatric Orthopaedics
Room number: CMC E2308.01
Mail Code: CMC E2300
Phone number: 214-456-6876
Project title: Identifying Human Genetic Factors Predisposing Children to Musculoskeletal Infection.
Evaluation and Management of Pediatric Musculoskeletal Infection According to Multi-Disciplinary Clinical Practice Guidelines.
Human subjects IRB approved project number (where applicable):
Brief Description of Project:
Children with musculoskeletal infection demonstrate a substantial variation in both the clinical manifestations of their disease as well as the severity of illness. Between January 1, 2002 and December 31, 2004, pediatric orthopaedic surgeons performed a retrospective review of the children who were treated for musculoskeletal infection at Children's Medical Center Dallas. (IRB# 082004-049, PI- L. Copley, MD.) The investigators' clinical perception led them to believe that there had been a marked change in the local epidemiology of musculoskeletal infection from 20 years before. The study identified increasing number of osteomyelitis and septic arthritis cases, the emergence of new forms of infection, and the emergence of new causative organisms. Further, we were able to identify a difference in the severity of illness with respect to primary diagnoses (osteomyelitis, septic arthritis, pyomyositis, and deep abscesses) and multiple diagnoses.
Currently, diagnostic categories such as erythrocyte sedimentation rate (ESR), C- reactive protein (CRP), blood cultures, radiographic studies and magnetic resonance imaging (MRI) are used to identify patients with musculoskeletal infections. However, in the face of changing epidemiology in the future, we realize there is a need to understand infection in pediatric patients on a genetic level for a long term solution. We believe that there may be a relationship between the genetic makeup of children and their chance of getting an infection.
The objectives of the study include: To establish a repository of samples including blood and DNA obtained from pediatric orthopaedic patients diagnosed with musculoskeletal infection: Osteomyelitis (bone infection), septic arthritis (joint infection), pyomyositis (muscle infection), and abscess (soft tissue infection);To evaluate human genetic factors that may influence the manifestations of musculoskeletal infection in children and to study the distinct gene expression patterns of children with various forms of Staphylococcus aureus infections to see if greater degrees of expressivity may be found with specific types of infection. David Sun will be involved in the transport of serum specimens collected to Texas Scottish Rite Hospital from enrolled subjects. He will also help in isolating DNA, PBMCs and total RNA. He will spend a major portion of his time at the TSRH molecular genetics laboratory doing the above procedures.
On the Identifying Human Genetic Factors Predisposing Children to Musculoskeletal
Infection Study, IRB# 052007-045, David Sun will be helping to build the DNA
and RNA repositories at Texas Scottish Rite Hospital. David Sun will work with
blood samples from children with Staph. aureus infections of the musculoskeletal
system as well as age matched, healthy control subjects. From those blood samples
David Sun will perform DNA extraction and freeze the isolate. David Sun will
be freezing total RNA samples in Tempus tubes.
After 2 years of sample collection (during David's second summer), we will perform candidate gene studies on the DNA samples. There are currently 6 candidate genes we would be looking for (NOS3, Bax gene, IL-1 alpha, Toll-like receptor, PTPN22R620W, and HLA Class II alleles), but by then there may be several more identified in the literature. We will also perform gene expression analysis using the RNA samples. This will determine the relative expression levels of the classifier genes previously identified by Ramilo et al., including: CXCL1, MMP9, JAG1, STAU, TRAM2, PPIB, P44S10, SEC24C, MGC2963, ACTG1, RGS2 and GAPD which have been found to be overly expressed in Staph aureus infections.
Children's Medical Center will be freezing and storing bacterial samples from all of our patients with Staph areus infections. We will use those samples to perform an analysis of the bacterial clone type, antibiotic resistance profile, and the identification of genetically encoded virulence factors.
The Evaluation and Management of Pediatric Musculoskeletal Infection According to Multi-Disciplinary Clinical Practice Guidelines study IRB# 032007-009 involves the ongoing prospective surveillance of the clinical manifestations of children with musculoskeletal infection. In this project David Sun will attend a daily patient discussion with our orthopedic team, attend a daily rounding process on the inpatient wards where we discuss the care issues of those patients. David Sun will go to the operating room to watch surgeries of children with infection and attend a weekly conference in which these cases are reviewed by the entire pediatric orthopedic faculty.
Previous Research Activities or Publications with Medical Students:
Hollmig, ST, Copley LA,Browne RH, Grande LM, Wilson PL. Deep Venous Thrombosis Associated with osteomyelitis in Children. Journal of Bone and Joint Surgery. Journal of Bone and Joint Surgery 89A (7) 1517-1523, 2007
Omar A Gafur, BA; Lawson A Copley, MD; Tyler S. Hollmig, BA; Richard H Browne, PhD; Lori A Thornton, RN, FNPC; Shellye E Crawford, RN, CPNP. The Impact of the current Epidemiology of Pediatric Musculoskeletal Infection on Evaluation and Treatment Guidelines. Journal of Pediatric Orhtopaedics.
Lectures and Presentations:
Hollmig, ST, Copley LA,Browne RH, Grande LM, Wilson PL. Deep Venous Thrombosis Associated with osteomyelitis in Children. 29th Annual Brandon Carrell Visiting Professorship of Texas Scottish Rite Hospital for Children. Dallas, Texas, 4/07
Omar A Gafur, B; Lawson A Copley, MD; The Changing Epidemiology Musculoskeletal Infection in Children. 29th Annual Brandon Carrell Visiting Professorship of Texas Scottish Rite Hospital for Children. Dallas, Texas, 4/07
Omar A Gafur, B; Lawson A Copley, MD; The Changing Epidemiology Musculoskeletal Infection in Children. 6th Annual Musculoskeletal Infection Soceity Meeting. San Diego, CA, 8/07 .