研究人员|Research Overview
Dr. Agrawal is focused on determining the genetic and molecular basis of congenital myopathies and various rare diseases. He is also interested in deciphering the applications of genomic sequencing in newborn medicine for screening and care.
His specific projects include:
- Identification of novel genes mutated in various rare and undiagnosed diseases:The goals of the project is to understand the genetic and molecular underpinnings of various orphan diseases that include n of 1 conditions, Ohtahara syndrome (a devastating seizure disorder), ROHHAD syndrome (a complex condition associated with rapid-onset obesity in early childhood, hypothalamic dysfunction, hypoventilation and autonomic dysfunction), mitochondrial disorders, various surgical conditions, including congenital pulmonary airway malformations, gastroschisis, various atresias (e.g. esophageal, intestinal), bladder exstrophies.
- Role of SPEG and cofilin-2 in skeletal muscle function:Mutations in these genes cause different types of congenital myopathy. He is utilizing conditional knockout mouse models of SPEG and cofilin-2 to determine their function and identify interacting proteins in skeletal muscles.
- Functional genomics of novel genes:Novel candidate genes identified in various rare diseases are often poorly understood. He is working on determining the function of several novel genes identified by his team.
- Application of genomics in newborn care:this includes utility of rapid exome or genome sequencing in the NICU and role of sequencing in newborn screening.
研究人员|Research Background
Dr. Agrawal obtained his MD from India where he also did his Pediatric Residency followed by neonatal training. He spent a few years in Melbourne, Australia working as Senior Registrar in Neonatology. He then came to Boston Children’s Hospital where he completed a Neonatal-Perinatal fellowship and Masters in Medical Science from Harvard Medical School. Currently, he is an Associate Professor of Pediatrics at Harvard Medical School (HMS) and Attending Neonatologist at Boston Children’s Hospital. He is also the Medical Director of the Gene Discovery Core, Manton Center of Orphan Disease Research based at Boston Children’s and Director of Neonatal Genomics Program. He has been funded by the NIH (K08, R01, U19) and has received several foundation grants.
选定的出版物
- Agrawal PB等。SPEG interacts with myotubularin (MTM1) and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet. published online on July 31, 2014.
- Agrawal PB等。Expanding the phenotype associated with NEFL mutation: Neuromuscular disease in a family with overlapping myopathic and neurogenic findings. Accepted to JAMA Neurology 2014.
- Sankaran VG et al. Rare complete loss-of-function provides insight into a pleiotropic genome-wide association study locus. Blood 2013 122(23):3845-7.
- Ozge Ceyhan et al. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Neurology 2013 81(14):1205-14.
- Agrawal PB等。正常的肌原纤维发育，然后是肌动蛋白在小鼠CFL2敲除中积累的进行性肌膜破坏，这表明Cofilin-2对肌肉维持的要求。Hum Mol Genet 2012; 21：2341-56。
- Majczenko K et al. Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. Am J Hum Genet 2012;91:365-71.
- Agrawal PB等。黑甲肌病与米仔由编码骨骼肌肌动蛋白结合蛋白Cofilin-2的CFL2基因突变引起。Am J of Hum Genet 2007; 80：162-7。PMC1785312。
- Agrawal PB等。Heterogeneity of nemaline myopathy cases with skeletal muscle -actin gene mutations. Ann Neurol 2004;56:86-96.