Pankaj Agrawal

Boston Children's Hospital and Harvard Medical School

MD DM

Boston Children's Hospital and Harvard Medical School

Genetic approaches to rare diseases, congenital myopathies

1. Agrawal PB, Strickland CD, Midgett C, Morales A, Newburger DE, Poulos MA, Ryan MM, Iannaccone ST, Crawford TO, Laing NG, Beggs AH. Heterogeneity of nemaline myopathy cases with skeletal muscle a-actin gene mutations. Ann. Neurol. 2004;56:86-96. 2. Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari VL, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR and Beggs AH (2007). 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. PMCID: PMC1785312. 3. Agrawal PB‡, Joshi M, Savic T, Chen Z, Beggs AH. 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(10): 2341-56. PMCID: PMC3335316. (‡ Corresponding author) 4 Chandonnet CJ, Kahlon PS, Rachh P, Degrazia M, Dewitt EC, Flaherty KA, Spigel N, Packard S, Casey D, Rachwal C, Agrawal PB‡. Health Care Failure Mode and Effect Analysis to Reduce NICU Line-Associated Bloodstream Infections. Pediatrics 2013;131(6):e1961-9. (‡ Corresponding author) 5. Ceyhan O*, Agrawal PB*, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC, Soemedi R, Vasli N, Iannaccone ST, Shieh PB, Shur N, Dennison JM, Lawlor MW, Laporte J, Markianos K, Fairbrother WG, Granzier H, Beggs AH. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Neurology 2013;81(14):1205-14. PMC3795603. * contributed equally to the manuscript. 6. Sankaran VG, Joshi M, Agrawal A, Schmitz-Abe K, Towne MC, Marinakis N, Markianos K, Berry GT, Agrawal PB‡. Rare complete loss-of-function provides insight into a pleiotropic genome-wide association study locus. Blood 2013;122(23):3845-7. (‡ Corresponding author) 7. Agrawal PB‡, Pierson CR, Joshi M, Liu X, Ravenscroft G, Moghadaszadeh B, Talabere T, Viola M, Swanson LC, Haliloğlu G, Talim B, Yau KS, Allcock RJN, Laing NG, Perrella MA, Beggs AH. SPEG interacts with myotubularin (MTM1) and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet. 2014;95(2):218-26. (‡ Corresponding author) 8. Subramanian K, Gianni D, Balla C, Assenza GE, Joshi M, Semigran M, Macgillivray TE, Van Eyk JE, Agnetti G, Paolocci N, Bamburg J, Agrawal PB, del Monte F. Cofilin-2 Phosphorylation and Sequestration In Myocardial Aggregates: Novel Pathogenetic Mechanisms For Idiopathic Dilated Cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1199-214. 9. Morton SU, Joshi M, Savic T, Beggs AH, Agrawal PB‡. Skeletal Muscle MicroRNA and Messenger RNA Profiling in Cofilin-2 Deficient Mice Reveals Cell Cycle Dysregulation Hindering Muscle Regeneration. PLoS One. 2015;10(4):e0123829. (‡ Corresponding author) 10. Bairdain S, Zurakowski D, Vargas SO, Stenquist N, McDonald M, Towne MC, Miller DT, Jennings RW, Kantor DB and Agrawal PB‡. Long-Gap Esophageal Atresia is a Unique Entity within the Esophageal Atresia Defect Spectrum. Accepted for publication in Neonatology (2016). (‡Corresponding author)

1. R01 2015-2020 SPEG is critical in skeletal muscle development and function (Active). NIH/NIAMS R01AR068429 PI: ($1,100,000) The goals of the project are to 1) Decipher the mechanisms responsible for skeletal muscle dysfunction due to SPEG deficiency 2) Investigate the role of SPEG in skeletal muscle growth and differentiation. 3) Determine the interrelationship between SPEG, desmin and MTM1 in the regulation of skeletal muscle function 2. U19 2013- 2018 Genome Sequence-Based Screening for Childhood Risk and Newborn Illness NICHD/NHGRI 1U19 HD077671 Co-PI (Project 2): ($135,750-total direct cost for the Agrawal portion) The major goals of the project are to evaluate potential integration of whole genome/exome sequencing into Newborn Screening. There are three subprojects: Project 1 is to acquire and analyze genomic datasets, Project 2 involves clinical research that will advance understanding of specific disorders and Project 3 is related to research into the ELSI implications of the possible implementation of genomic sequencing of newborns.  2013-2018 3. R01 Genes and Therapies for Centronuclear Myopathies NIH/NIAMS R01 AR044345-15A1 Project Scientist: ($45,250-total direct cost for the Agrawal portion) The major goals of the project are to identify novel genes associated with centronuclear myopathies and therapeutic approaches using zebrafish as an animal model. 2016-2020 4. UM1 A Joint Center for Mendelian Genomics. A collaboration between Broad Institute of Harvard & MIT, Rockefeller University and Boston Children’s Hospital. NIH/NHGRI/NHLBI UM1HG008900 Co-I ($18,100- total direct cost for the Agrawal portion) The Joint Center will serve the wider inherited disease community (including other CMGs) by rapidly and openly releasing data, methods, software and candidate genes.