My long-term research interests are to understand the genetic basis of various rare diseases that present very early in life, with a goal to decipher various therapeutic approaches. I have been working to determine the genetic basis of various congenital myopathies that are quite rare, and have identified several genes including cofilin-2 (CFL2), titin (TTN) and striated preferentially expressed gene (SPEG) to be mutated in those conditions. I have utilized various models including zebrafish and mouse models to determine the pathogenicity of those mutations. Further, as Medical Director and Principal Investigator of the Gene Discovery Core (GDC), the Manton Center for Orphan Disease Research I am enrolling patients with various orphan diseases, and have identified novel genes mutated in various conditions including Ohtahara syndrome (a devastating seizure disorder presenting in neonatal age), ROHHAD syndrome (a complex condition associated with rapid-onset obesity in early childhood, hypothalamic dysfunction, hypoventilation and autonomic dysfunction) and mitochondrial disorders. In addition, I am enrolling young patients with various undiagnosed and surgical conditions, including congenital pulmonary airway malformations, gastroschisis, various atresias (e.g. esophageal, intestinal) to our database, and understand the genetic underpinnings.
About Pankaj B. Agrawal
Pankaj Agrawal is an Assistant Professor of Pediatrics at Harvard Medical School (HMS). He is a neonatologist by training, with research focused on the identification of genetic and molecular basis of various orphan diseases presenting in early life. He was recruited to the Harvard Neonatal-Perinatal Medicine Fellowship Program at Boston Children’s Hospital (BCH) from Monash University, Melbourne in 2000. During his fellowship at BCH, he was extensive trained in translational research, and was awarded Masters in Medical Science (MMSC) from HMS. Since 2003, he has been a Faculty in the Division of Newborn Medicine, BCH. In 2010, he was appointed the Medical Director of the Gene Discovery Core, Manton Center at BCH focused on determining the genetic basis of various rare diseases. He has published extensively, has been funded by various local and NIH grants, and has received awards for his clinical and research work. He is one of the core members of the Neonatology team at BCH, and spends few months a year in the NICU, managing extremely sick babies and training and supervising neonatal fellows and nurse practitioners in critical decision-making, neonatal procedures, and parental communications.
1. Agrawal PB et al. SPEG interacts with myotubularin (MTM1) and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet. published online on July 31, 2014.
2. Agrawal PB et al. Expanding the phenotype associated with NEFL mutation: Neuromuscular disease in a family with overlapping myopathic and neurogenic findings. Accepted to JAMA Neurology 2014.
3. 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.
4. Ozge Ceyhan et al. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Neurology 2013 81(14):1205-14.
5. Agrawal PB et al. Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance. Hum Mol Genet 2012;21:2341-56.
6. 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.
7. Agrawal PB et al. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J of Hum Genet 2007;80:162-7. PMC1785312.
8. Agrawal PB et al. Heterogeneity of nemaline myopathy cases with skeletal muscle -actin gene mutations. Ann Neurol 2004;56:86-96.