Divisions
Medical Genetics and Genomic Medicine
Division Faculty
Education and Training
Research
Phillips Lab
Joy D. Cogan, Ph.D.
Hamid Lab
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Current Projects

Familial Defects of the GH Synthetic Pathway
We have shown that targeted siRNAs can specifically degrade dominant negative GH transcripts that cause Isolated Growth Hormone Deficiency type II (IGHD II) in cultured cells, lymphoblastoid cells (LCs) from IGHD II subjects, and by mating siRNA expressing mice with a transgenic mouse model of IGHD II.  We are determining if allele specific siRNAs can be delivered by nanoparticles with GHRHR peptide tags, via the bloodstream to destroy mutant transcripts and restore GH secretion in IGHD II mice. We also are identifying and using FDA approved medications to decrease transcripts that cause IGHD II in LCs from IGHD II subjects and to restore GH secretion in IGHD II mice.

Shariat N, Ryther RCC, Phillips JA III, Robinson ICAF, Patton JG. Rescue of Pituitary Function in a Mouse Model of Isolated Growth Hormone Deficiency Type II by RNAi. Endocrinology 149: 580-586, 2008.

Hereditable Pulmonary Arterial Hypertension (HPAH)
We discovered that BMPR2 mutations cause HPAH. We are now determining the contributions of BMPR2 and modifier genes to the reduced penetrance that is observed in HPAH.

Phillips JA III, Poling JS, Phillips CA, Stanton KC, Austin ED, Cogan JD, Wheeler L, Yu  C, Dietz HC and Loyd JE. Synergistic heterozygosity for functional TGFβ1 SNPs and BMPR2 mutations modulates the age of diagnosis of Familial Pulmonary Arterial Hypertension (FPAH). Genetics in Medicine 10: 359-365, 2008.

Hamid R, Cogan JD, Hedges LK, Phillips JA III, Newman JH, Loyd JE: Penetrance of Pulmonary Arterial Hypertension is modulated by the expression of normal BMPR2 allele. Human Mutation. First published ahead of print Feb 17, 2009 as doi: 10.1002/humu20922.

Idiopathic Pulmonary Fibrosis (IPF)
Studies of IPF led to our discovery that surfactant protein C (SFTPC) or telomerase (TERT/TERC) mutation causes Familial Pulmonary Fibrosis (FPF).  We are now beginning studies to identify genetic defects in the SFTP or telomerase pathways that cause FPF.

Armanios M, Chen J J-L, Cogan JD, Alder J K, Ingersol R G, Markin C, Lawson W E, Xie M, Vulto I, Phillips J A III, Lansdorp P M, Greider CW and Loyd JE: Telomerase Mutations in Families with Idiopathic Pulmonary Fibrosis. New Eng J Med 356: 1317-1326, 2007.



 
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