Katia Sol-Church, Ph.D.

Director, Biomolecular Core Laboratory
Assistant Professor of Pediatrics, Thomas Jefferson University

Contact

Sol-Church

Alfred I. duPont Hospital for Children
1600 Rockland Road
P.O. Box 269
Wilmington, DE 19899

Phone: (302) 651-6705
Fax: (302) 651-6767
E-mail: ksolchur@nemours.org

Education

M.S.: Université Paul Sabatier, France
Ph.D.: McGill University, Canada
Postdoctoral: Dupont-Merck Pharmaceuticals

Research Interests

Research in the Biomolecular Core Laboratory is focused on identifying the genetic basis and understanding the molecular mechanisms underlying complex disorders. Dr. Sol-Church's interest is primarily in disorders associated with skeletal dysplasia and cancer.

The main focus of the lab is to understand the effect of gain of function mutations in children with Costello Syndrome (CS), a disorder that affects multiple organ systems of the body and is characterized by short stature; mental retardation; redundant loose skin, papillomata and predisposition for heart defect and cancer (rhabdomyosarcoma). CS children carry germline mutation in the HRAS gene, a key regulator of the MAPK signaling cascade controlling cell growth regulation, cell adhesion, motility, and apoptosis. Our goal is to identify genomic factors/modifiers, outside of the well-characterized mutation, that may influence expressivity of the disease. These genomics and functional studies may reveal other pathways downstream of RAS that may contribute to the varied phenotypes of these related syndromes and help develop a better understanding of the cellular mechanisms disrupted in these disorders.

Costello syndrome shares many clinical findings with cardio-facio-cutaneous (CFC) syndrome, which is caused by mutation in other genes of the MAPK pathway, namely BRAF, MEK1 and MEK2 genes. Little is known about the contribution of each mutation to the function of the mutated proteins in CS and CFC patients. Thus, using cell lines derived from patients, we will study how changes in gene expression impact the signaling cascade and correlate with the patient's recorded clinical history and determine whether prognostic tools can be derived to predict disease course in new patients.

These studies will provide us with a better understanding of the disease pathology and perhaps will allow new therapeutic avenues. The ultimate goal of this research is to provide Clinicians with tools that can help improve pediatric supportive care and/or therapeutic intervention.

Current Projects

• Identification of germline mutations in CS and CFC
• Loss of heterozygosity and loss of imprinting in Rhaddomyosarcoma (RMS) in CS patients
• Search for genetic modifier of disease expressivity in CS
• Effect of germline mutation on MAPK pathway activation

Research Group

• Karen Gripp, M.D. - Division Chief, Genetics
• Linda Nicholson, M.S. - Genetic Councelour
• Abigail Agbulos, B.S. - Undergraduate Student, University of Delaware
• Jennifer Frenck, B.S. - Assistant Director, Senior Research Assistant
• Deborah Stabley, B.S. - Senior Research Assistant II
• Peter Geller - Volunteer

Biomolecular Core Laboratory Group

Selected Publications

Sol-Church K and Gripp K. Molecular Basis of Costello Syndrome. 2008 (in press) in Martin Zenker (ed), Monographs in Human Genetics Volume 17: Noonan Syndrome and Related Disorders A Matter of Deregulated Ras Signaling.

Zhang H, Sol-Church K, Rydbeck H, Stabley D, Spotila LD, Devoto M. High resolution linkage and linkage disequilibrium analyses of chromosome 1p36 SNPs identify new positional candidate genes for low bone mineral density. Osteoporos Int. 2008 Jul 3. [Epub ahead of print].

Cooper CR, Graves B, Pruitt F, Chaib H, Lynch JE, Cox AK, Sequeria L, van Golen KL, Evans A, Czymmek K, Bullard RS, Donald CD, Sol-Church K, Gendernalik JD, Weksler B, Farach-Carson MC, Macoska JA, Sikes RA, Pienta KJ. Novel surface expression of reticulocalbin 1 on bone endothelial cells and human prostate cancer cells is regulated by TNF-alpha. J Cell Biochem. 2008 Jun 17. [Epub ahead of print]

Gripp KW, Innes AM, Axelrad ME, Gillan TL, Parboosingh JS, Davies C, Leonard NJ, Lapointe M, Doyle D, Catalano S, Nicholson L, Stabley DL, Sol-Church K. Costello syndrome associated with novel germline HRAS mutations: an attenuated phenotype? Am J Med Genet A. 2008, 146(6):683-690.

Axelrad ME, Nicholson L, Stabley DL, Sol-Church K, Gripp KW. Longitudinal assessment of cognitive characteristics in Costello syndrome. Am J Med Genet A. 2007, 143(24):3185-3193.

Al-Rahawan MM, Chute DJ, Sol-Church K, Gripp KW, Stabley DL, McDaniel NL, Wilson WG, Waldron PE. Hepatoblastoma and heart transplantation in a patient with cardio-facio-cutaneous syndrome. Am J Med Genet A. 2007, 143(13):1481-1488.

Gripp KW, Lin AE, Nicholson L, Allen W, Cramer A, Jones KL, Kutz W, Peck D, Rebolledo MA, Wheeler PG, Wilson W, Al-Rahawan MM, Stabley DL, Sol-Church K. Further delineation of the phenotype resulting from BRAF or MEK1 germlinemutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome. Am J Med Genet A. 2007, 143(13):1472-1480.

Ioannidis JP, Ng MY, Sham PC, Zintzaras E, Lewis CM, Deng HW, Econs MJ, Karasik D, Devoto M, Kammerer CM, Spector T, Andrew T, Cupples LA, Duncan EL, Foroud T, Kiel DP, Koller D, Langdahl B, Mitchell BD, Peacock M, Recker R, Shen H, Sol-Church K, Spotila LD, Uitterlinden AG, Wilson SG, Kung AW, Ralston SH. Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass. J Bone Miner Res. 2007, 22(2):173-183.

Gripp KW, Stabley DL, Nicholson L, Hoffman JD, Sol-Church K. Somatic mosaicism for an HRAS mutation causes Costello syndrome. Am J Med Genet A. 2006, 140(20):2163-2169.

Barthold JS, Si X, Stabley D, Sol-Church K, Campion L, McCahan SM. Failure of shortening and inversion of the perinatal gubernaculum in the cryptorchid long-evans orl rat. J Urol. 2006, 176(4 Pt 1):1612-1617.

Sol-Church K, Stabley DL, Nicholson L, Gonzalez IL, Gripp KW. Paternal bias in parental origin of HRAS mutations in Costello syndrome. Hum Mutat. 2006, 27(8):736-741.

Gripp KW, Lin AE, Stabley DL, Nicholson L, Scott CI Jr, Doyle D, Aoki Y, Matsubara Y, Zackai EH, Lapunzina P, Gonzalez-Meneses A, Holbrook J, Agresta CA, Gonzalez IL, Sol-Church K. HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. Am J Med Genet A. 2006, 140(1):1-7.

Zhang H, Barnoski BL, Sol-Church K, Stabley DL, Martin-Deleon PA. Murine Spam1 mRNA: involvement of AU-rich elements in the 3'UTR and antisense RNA in its tight post-transcriptional regulation in spermatids. Mol Reprod Dev. 2006, 73(2):247-255.

Holbrook JF, Stabley D, Sol-Church K. Exploring whole genome amplification as a DNA recovery tool for molecular genetic studies. J Biomol Tech. 2005, 16(2):125-133.

Devoto M, Spotila LD, Stabley DL, Wharton GN, Rydbeck H, Korkko J, Kosich R, Prockop D, Tenenhouse A, Sol-Church K. Univariate and bivariate variance component linkage analysis of a whole-genome scan for loci contributing to bone mineral density. Eur J Hum Genet. 2005, 13(6):781-788.