Areas of Expertise:
Genetic causes of neonatal disease
Locations: CHOP Newborn Care at the Hospital of the University of Pennsylvania; Main Campus
Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)
I am a neonatologist with a research interest in the genetic basis of cardiac development and the molecular mechanisms of congenital heart disease. One of my research projects focuses on understanding DiGeorge syndrome, a relatively common syndrome affecting newborns. Patients with DiGeorge syndrome can have a wide variety of problems including deformities of the head and face, speech problems due to improper separation of the oral and nasal cavities, cleft palate, absence or incomplete development of the thymus and parathyroid glands, and problems with the aortic arch and outflow tract of the heart. The cardiac defects associated with the syndrome, often severe, are present in 75 percent of patients and contribute significantly to morbidity.
Most patients with DiGeorge syndrome carry a large genomic deletion of chromosome 22q11. One gene within this commonly deleted region is the transcription factor, TBX1. My colleagues and I identified the molecular mechanism by which a human TBX1 mutation results in DiGeorge syndrome. Additionally, through work with embryonic stem cells, we identified a new Tbx1 interacting protein that is critical for the earliest stages of embryonic development and may be important in understanding the function of Tbx1. Understanding the mechanisms of Tbx1 function will provide insight into both normal and abnormal cardiac development.
A second research project is to identify genes that are critical for differentiating the left sixth aortic arch artery into the ductus arteriosus. Patent ductus arteriosus, a condition in which a child's ductus arteriosus does not close after birth, is a major cause of neonatal morbidity and therapeutic options are limited. A better understanding of what differentiates the left sixth aortic arch artery from the other aortic arch arteries during development will elucidate potential targets for future pharmacologic treatment strategies and has the potential to improve long-term outcomes among extremely low birthweight neonates. Tools used for this project include RNA transcript microarrays and in vivo disease models.
- Education and Training
MD - University of Pennsylvania School of Medicine, Philadelphia, PA
Pediatrics - Brown University/Hasbro Children's Hospital, Providence, RI
Neonatal-Perinatal Medicine - The Children's Hospital of Philadelphia, Philadelphia, PA
- Titles and Academic Titles
Assistant Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania Medical School
- Departments and Services
- Research Interests
Genetic basis of cardiac development
Molecular mechanisms of congenital heart disease with emphasis on DiGeorge Syndrome
Shelton E, Ector G, Galindo C, Hooper C, Brown N, Wilkerson I, Pfaltzgraff E, Paria B, Cotton R, Stoller JZ, Reese J: Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone. Physiol Genomics. 2014 Jul 1;46(13):457-66. Epub 2014 May 1. Read the abstract.
Zhang T, Liu J, Zhang J, Thekkethottiyil EB, Macatee TL, Ismat FA, Wang F, Stoller JZ. Jun is required in Isl1-expressing progenitor cells for cardiovascular development. PLoS One. 2013;8(2):e57032. doi: 10.1371/journal.pone.0057032. Epub 2013 Feb 21. Read the abstract
Stoller JZ, Demauro SB, Dagle JM, Reese J. Current Perspectives on Pathobiology of the Ductus Arteriosus. J Clin Exp Cardiolog. 2012 Jun 15;8(1). pii: S8-001. Read the abstract
Posters and Presentations
Pan H. Zhang T. De Mesmaeker J. Neve A, Benson MA, Latney BC, Werner P, Goldmuntz E, Bhattacharya S, Stoller, JZ. A Dominant Negative JUN mutant is associated with human congenital heart disease and alters a physical and functional interaction with TBX1 (Platform Presentation). Weinsten Cardiovascular Development Conference. 2013 May 16-18, Tucson, AZ.
Pan H, Zhang T, Kraft CA, Subbaraj I, De Mesmaeker J, Latney BC, Goldmuntz E, Bhattacharya S, Stoller, JZ. TBX1 Interacts with JUN and a Dominant Negative JUN Missense Mutation Is Associated with Congenital Heart Disease (Platform Presentation). Eastern Society for Pediatric Research. 2013 Mar 22, Philadelphia, PA.
Pan H, Zhang T, Kraft CA, Subbaraj I, De Mesmaeker J, Latney BC, Goldmuntz E, Bhattacharya S, Stoller, JZ. TBX1 Interacts with JUN and a Dominant Negative JUN Missense Mutation Is Associated with Congenital Heart Disease (Platform Presentation). Pediatric Academic Societies (PAS) Annual Meeting. 2013 May 4-7, Washington DC.