Musculoskeletal Inherited Disease Lab

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Musculoskeletal Inherited Disease Lab

About the Musculoskeletal Inherited Disease Lab

The Musculoskeletal Inherited Disease Research Lab (MID lab) focus is primarily on the research and molecular analyses of pediatric neuromuscular, cardiac, and skeletal dysplasia diseases.

Lab Head

Principal Investigator

Vicky L. Funanage, PhD 
Director of Biomedical Research of The Nemours Foundation
Director, Molecular Diagnostic Lab, Nemours Children’s Hospital, Delaware; Chief, Musculoskeletal Inherited Disease Research Program, Department of Medical Research, Nemours Children’s Hospital, Delaware; Associate Professor of Pediatrics, Jefferson Medical College, Thomas Jefferson University; Adjunct Professor, College of Health Sciences, University of Delaware

Susan M Kirwin, BS

Assistant Director, MDL
(302) 651-6777


Nemours Children’s Hospital, Delaware
1600 Rockland Road
Wilmington, DE 19803
Phone: (302) 651-6819
Fax: (302) 651-6876

Current Research

Research Interests & Projects

Our work encompasses rare genetic diseases seen by the clinicians at Nemours, and we work collaboratively to further understand and develop genetic testing for these disorders.

Effect of TRPV4 Mutation on Calcium Channel Function

Pathogenic TRPV4 mutations have been identified in a number of musculoskeletal conditions, including dominant brachyolmia, Kozlowski type spondylometaphyseal dysplasia, metatropic dysplasia, Maroteaux type spondylo-epiphyseal dysplasia, and parastremmatic dysplasia, as well as in several neurological disorders, including hereditary motor and sensory neuropathy type IIC, congenital spinal muscular atrophy, Charcot-Marie-Tooth 2A, and scapuloperoneal spinal muscular atrophy. 

This project involves the study of channel activity in cultured cells (fibroblasts, bone, and cartilage) isolated from metatropic dysplasia patients with TRPV4 mutations. Our current work conducted both at Nemours and in collaboration with Dr. Randall Duncan of the University of Delaware, has demonstrated that increased intracellular calcium levels are correlated with TRPV4 gain-of-function mutations. This IRB approved study is currently enrolling patients to aid in our understanding of how this altered channel activity leads to the severe pathology of metatropic dysplasia.  

Current Research Group

Vicky L. Funanage, PhD — Principal Investigator

Michael Bober, MD, PhD — Co-director, Skeletal Dysplasia Program, Division of Medical Genetics

William Mackenzie, MD — Chair, Department of Orthopedics, Nemours Children’s Hospital, Delaware

Susan M. Kirwin, BS — Senior Research Associate/MID Laboratory Manager

Randall Duncan, PhD — Chair, Department of Biological Sciences, University of Delaware

Lauren Hurd, BS — University of Delaware graduate student

Functional Analysis of TBX5/NKX2.5 Mutations in HLHS

The second area of interest involves hypoplastic left heart syndrome (HLHS). Congenital heart malformations are the most common birth defect, and are the leading cause of infant mortality within the first year of life. HLHS is characterized by the underdevelopment of several structures on the left side of the heart: the left ventricle is underdeveloped; the mitral valve and aortic valve are small or may not be developed; the ascending portion of the aorta is small, with possible aortic stenosis, atresia of the aortic arch, and/or patent ductus arteriosis. 

Our research, done in collaboration with Dr. Christian Pizarro, has focuses on determining the genetic cause(s) of this rare disease. We have screened DNA samples from patients with congenital heart defects, and have found a cluster of variations within exon 8 of the TBX5 gene. This domain of the protein interacts with transcription factors that can regulate cardiac development, and suggests a potential mechanism by which alterations in specific cardiac transcription factors may lead to HLHS. Future studies include gene sequencing of the cardiac transcription factors NKX2.5, GATA4, and other potential candidate genes, as well as functional studies.

Current Research Group

Vicky L. Funanage, PhD — Principal Investigator

Christian Pizarro, MD — Director, Nemours Cardiac Center

Susan M. Kirwin, BS — Senior Research Associate/MID Laboratory Manager

Diabetic and Cardiovascular Risk in Breast- and Formula-Fed

Previous epidemiological studies have shown that breastfeeding reduces the incidence of obesity in childhood, and that this effect is dose-related. That is, the duration of breastfeeding directly relates to a decreased risk of developing obesity in childhood. In a previous Nemours-funded study, we followed 82 mother/infant pairs (enrolled as exclusive breast-fed or formula-fed families) from a local pediatric practice. Breast milk leptin levels were measured over the first 12 weeks of lactation and correlated to infant growth, adiposity, and satiety. We found that leptin levels in breast milk influenced satiety, especially in male infants.

This cohort provided us a unique opportunity to perform a follow-up study almost a decade later to measure various aspects of adiposity (BMI and arm fat) as well as biomarkers of diabetes and cardiovascular disease in serum of these children. If breastfeeding reduces these risk factors, it will offer a cost-effective means by which to reduce the incidence of obesity and its associated co-morbidities in children. We are interested in determining whether breast feeding is a protective factor in the development of obesity, diabetes and/or cardiovascular disease.

Current Research Group

Vicky L. Funanage, PhD — Principal Investigator

Susan M. Kirwin, BS — Senior Research Associate/MID Laboratory Manager

Sandra Hassink, MD — Director of the Nemours Obesity Initiative, Nemours Children’s Hospital, Delaware

Representative Publications

Kirwin SM, Bhandari V, Dimatteo D, Barone C, Johnson L, Paul S, Spitzer AR, Chander A, Hassink SG, Funanage VL. Leptin enhances lung maturity in the fetal rat. Pediatr Res. 2006 Aug;60(2):200-4.

O'Connor D, Funanage V, Locke R, Spear M, Leef K. Leptin is not present in infant formulas. J Endocrinol Invest. 2003 May;26(5):490

Alavi K, Schwartz MZ, Prasad R, O'connor D, Funanage V. Leptin: a new growth factor for the small intestine. J Pediatr Surg. 2002 Mar;37(3):327-30.

Spear ML, Hassink SG, Leef K, O'Connor DM, Kirwin SM, Locke R, Gorman R, Funanage VL. Immaturity or starvation? Longitudinal study of leptin levels in premature infants. Biol Neonate. 2001 Jul;80(1):35-40.

Resto M, O'Connor D, Leef K, Funanage V, Spear M, Locke R. Leptin levels in preterm human breast milk and infant formula. Pediatrics. 2001 Jul;108(1):E15.

Smith-Kirwin SM, O'Connor DM, De Johnston J, Lancey ED, Hassink SG, Funanage VL. Leptin expression in human mammary epithelial cells and breast milk. J Clin Endocrinol Metab. 1998 May;83(5):1810-3.

Hassink SG, de Lancey E, Sheslow DV, Smith-Kirwin SM, O'Connor DM, Considine RV, Opentanova I, Dostal K, Spear ML, Leef K, Ash M, Spitzer AR, Funanage VL. Placental leptin: an important new growth factor in intrauterine and neonatal development? Pediatrics. 1997 Jul;100(1):E1.