Title
Assistant Professor of Pediatrics

Education
BS – University of Iowa; 1986
MD – University of Iowa; 1990

Postgraduate Training
Residency – University of Virginia
Pediatric Rheumatology and Immunology Fellowship – University of Virginia
Post-Doctoral Research Fellowship, University of Virginia
Research Associate in Microbiology Pediatric Fellowship, University of Virginia

Clinical Interests
Inflammatory Disorders in Childhood including all forms of Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus, Vasculitis Syndromes and rare inflammatory conditions including Chronic Recurrent Multifocal Osteomyelitis, SAPHO Syndrome and Periodic Fever Syndromes

Research Interests
Genetic Aspects of Inflammatory Disorders, current research projects focus on determining the genetic basis of Chronic Recurrent Multifocal Osteomyelitis, SAPHO Syndrome and Lupus

Chronic Recurrent Multifocal Osteomyelitis (CRMO).
CRMO is a chronic inflammatory disease of unknown etiology. It primarily affects children and results in recurrent fever and the development of multiple inflammatory bone lesions. It is frequently seen in association with other, more common, inflammatory disorders such as psoriasis, inflammatory bowel disease and cutaneous pustulosis making it a particularly interesting disorder to study. There are reports of affected siblings in the literature and published evidence for a susceptibility locus for CRMO on human chromosome 18q suggesting a genetic component to its etiology. In addition, there is a syndromic, autosomal recessive disorder, called Majeed syndrome, in which CRMO is a major clinical feature. The genetic basis of CRMO is further supported by the existence of a similar disorder in the mouse (cmo, chronic multifocal osteomyelitis) resulting from a spontaneous mutation that is inherited as an autosomal recessive trait. In collaboration with Dr. Hatem El-Shanti in the Division of Medical Genetics, we are in the process of dissecting the genetic basis of CRMO utilizing all 3 available models. First, the El-Shanti lab has recently demonstrated that Majeed Syndrome, a syndromic form of CRMO, is caused by defects in the LPIN2 gene. Second, my laboratory has recently identified the gene defect in the cmo mouse and are currently performing experiments to determine the immunologic abnormalities in these mice. Third, we (El-Shanti and Ferguson) are collecting DNA from patients with sporadic (non-syndromic) CRMO to see if we can determine the gene defect(s) in these patients. The goal of this research is to understand the genetic basis of chronic, non-infectious osteomyelitis. Knowledge about the gene defect(s) present in CRMO may aid in the understanding of the pathways of inflammation involved, not only in CRMO, but also in the inflammatory disorders that frequently accompany this disorder such as psoriasis and inflammatory bowel disease

Systemic Lupus Erythematosus (SLE)
SLE is a phenotypically diverse, multi-system autoimmune disorder that is caused by ill-defined interaction(s) between environmental and genetic factors. Genome wide linkage analysis of SLE multiplex families suggests there is significant racial and genetic heterogeneity, further complicating the genetic dissection of this disorder. Fortunately, there are phenotypically similar mouse models of lupus; including genetically engineered and spontaneous models. Most of the investigative work in the field has focused on identifying disease susceptibility loci; however, there are experimental data that suggest disease resistance genes are also important, The non-autoimmune New Zealand White (NZW) mouse does not develop lupus despite harboring the best characterized lupus susceptibility intervals and a disease permissive major histocompatibility locus H-2z/z suggesting that the NZW genome contains allelic polymorphisms that negatively regulate the phenotypic expression of lupus susceptibility gene(s). We hypothesize that experimental crosses between NZW and C57BL/6.FcgammaRIIB-deficient mice will allow the identification of NZW-derived intervals that attenuate the lupus phenotypes in this genetically engineered murine model of lupus. We are 1) mapping quantitative trait loci (QTL) that modulate the FcgammaRIIB-/- lupus phenotype in order to identify NZW-derived intervals that are associated with suppression of the phenotype and 2) we will then construct chromosome substitution strains (CSS) in order to dissect the genetic contribution of these individual QTL. Identification of QTL that modulate the lupus phenotype and the subsequent development of QTL containing CSS will lay the foundation for the future functional assessment of the lupus-attenuating QTL and for candidate gene analysis. Understanding the genetic basis of disease resistance could facilitate the development of novel therapeutic approaches for treating this devastating disease.

Lab Members
Xinyu Bing, RA

Collaborative Projects With
Tom Waldschmidt

Model System
Murine & human

Recent Publications (doc)

Back to the Department of Pediatrics

Division of Rheumatology

Recent Publications (doc)

Contact Information:
Office: 319-356-1608
Fax: 319-356-7659
E-mail: polly-ferguson@uiowa.edu