Dr. ” leads a molecular research group that is focused on disease gene discovery using positional cloning/candidacy techniques and characterization of the biological roles of such genes in disease pathogenesis. The focus of the laboratory currently is on those traits that are associated with heart malformations. In the past few years, the lab has identified disease genes for Char and Noonan syndromes. The former is TFAP2B, which encodes a transcription factor of the AP-2 family, and the latter is PTPN11, which include the protein tyrosine phosphatase SHP-2. They are studying the roles of these disease genes in normal developmental and homeostatic processes as well as in disease pathogenesis. They are actively studying additional human genetic traits, both simple and complex, to identify additional disease genes with a particular focus on traits with cardiovascular abnormalities. After recruiting families of adequate size inheriting disorders, the research group undertakes genome-wide scans with polymorphic DNA markers to identify genetic loci through linkage analysis, and then identify disease genes from among known or predicted genes residing in disease loci. The latter relies heavily on bioinformatics, including several software packages that predict genes and protein function. Ongoing biologic studies include site-directed mutagenesis, expression of wild type and mutant proteins in vitro and in eukaryotic cell culture, immunolocalization of proteins, creation of transgenic mice, and phenotyping of mouse models. Through collaborative efforts, they are also studying disease genes in other model organisms such as Drosophila melanogaster and Xenopus laevis. This work is funded through awards from the NIH and the March of Dimes.
The Division has acquired new technology and recruited new faculty to explore
emerging non-invasive technologies in the functional and/or morphological assessment
of pediatric and congenital heart disease (CHD). Recently completed studies
include one on the use of telemedicine in fetal echocardiography and another
on our 10-year experience with diagnosing occult coronary artery anomalies.
Currently, new Doppler and related echocardiographic techniques are being investigated
for the assessment of diastolic function. A state of the art GE ultrasound
imager was acquired in 2003, in part because it is at the leading edge for
technologies such as Tissue Doppler Imaging.
In our pediatric noninvasive laboratory,
Lai, “, “, and ” have collaborated in comparing
cardiac MRI and Doppler Tissue Imaging in the assessment of right ventricular
function in patients postoperative for CHD repairs. Dr. Nielsen, recruited
to develop congenital cardiac MRI at Mount Sinai has spearheaded research
investigating the ability of MRI to evaluate RV function. His recent work details
methods to separately evaluate the function of the sinus and infundibular portions
of the RV in patients after tetralogy of Fallot repair.
Drs. Gelb and Lai are participating in a large NIH-funded SCCOR grant/translational
research project headed by Dr. Woodrow Benson at Cincinnati Children’s Hospital.
The goal is to define the genetic basis for congenital heart defects, with
echocardiography being used to describe the phenotypes. Mount Sinai’s Pediatric
Echocardiography Laboratory is one of two core echocardiography laboratories
and the goal for our group will be to recruit patients with specific lesions
that are defined echocardiographically and thought to have a strong genetic
predisposition. We will request DNA from these patients and their family members,
and the DNA will be sent for genetic investigation to Dr. Gelb’s and similar
laboratories as well as being banked for future investigations.
Another area of clinical research the Division has targeted involves the development
of novel invasive catheterization technologies in the treatment of Pediatric
and Adult Patients with congenital or acquired heart disease, including Dr.
Director of the Congenital Cardiac Catheterization Laboratory, is exploring
the roles of intracardiac echocardiography (ICE) and a radiofrequency perforation
device. He has collaborated with the Division of Cardiology of the Samuel Bronfman
Department of Medicine in the use of radiofrequency catheter transseptal perforation
and intracardiac echocardiographyto aid in the transcatheter treatment of mitral
stenosis. Dr. Love is also the institutional principal investigator for a multi-institutional
trial of device closure of patent formamen ovale in adult with occult thromboembolic