Research

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Pankaj B. Agrawal, MBBS, MMSc

Pankaj B. Agrawal
Department:
Medicine Research
Division
Newborn Medicine Research
Hospital Title:
Assistant in Medicine
Academic Title:
Assistant Professor of Pediatrics, Harvard Medical School
Research Focus Area:
Orphan/Rare diseasesCongenital myopathies
Contact Via Email
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Research Overview

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.

Key Publications

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.


Publications

Publications powered by Harvard Catalyst Profiles
  1. Bairdain S, Zurakowski D, Vargas SO, Stenquist N, McDonald M, Towne MC, Miller DT, Jennings RW, Kantor DB, Agrawal PB. Long-Gap Esophageal Atresia Is a Unique Entity within the Esophageal Atresia Defect Spectrum. Neonatology. 2016 Oct 19; 111(2):140-144.
  2. Smedemark-Margulies N, Brownstein CA, Vargas S, Tembulkar SK, Towne MC, Shi J, Gonzalez-Cuevas E, Liu KX, Bilguvar K, Kleiman RJ, Han MJ, Torres A, Berry GT, Yu TW, Beggs AH, Agrawal PB, Gonzalez-Heydrich J. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia. Cold Spring Harb Mol Case Stud. 2016 Sep; 2(5):a001008.
  3. Haldar P, Agrawal P. India's Preparedness for Introduction of IPV and Switch from tOPV to bOPV. Indian Pediatr. 2016 Aug 7; 53 Suppl 1:S44-S49.
  4. Lacy JN, Ulirsch JC, Grace RF, Towne MC, Hale J, Mohandas N, Lux SE, Agrawal PB, Sankaran VG. Exome sequencing results in successful diagnosis and treatment of a severe congenital anemia. Cold Spring Harb Mol Case Stud. 2016 Jul; 2(4):a000885.
  5. Joshi M, Anselm I, Shi J, Bale TA, Towne M, Schmitz-Abe K, Crowley L, Giani FC, Kazerounian S, Markianos K, Lidov HG, Folkerth R, Sankaran VG, Agrawal PB. Mutations in the substrate binding glycine-rich loop of the mitochondrial processing peptidase-a protein (PMPCA) cause a severe mitochondrial disease. Cold Spring Harb Mol Case Stud. 2016 May; 2(3):a000786.
  6. 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.
  7. Subramanian K, Gianni D, Balla C, Assenza GE, Joshi M, Semigran MJ, Macgillivray TE, Van Eyk JE, Agnetti G, Paolocci N, Bamburg JR, 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 Mar 31; 65(12):1199-214.
  8. Thaker VV, Esteves KM, Towne MC, Brownstein CA, James PM, Crowley L, Hirschhorn JN, Elsea SH, Beggs AH, Picker J, Agrawal PB. Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome. J Clin Endocrinol Metab. 2015 May; 100(5):1723-30.
  9. Agrawal PB, Joshi M, Marinakis NS, Schmitz-Abe K, Ciarlini PD, Sargent JC, Markianos K, De Girolami U, Chad DA, Beggs AH. Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings. JAMA Neurol. 2014 Nov; 71(11):1413-20.
  10. Agrawal PB, Pierson CR, Joshi M, Liu X, Ravenscroft G, Moghadaszadeh B, Talabere T, Viola M, Swanson LC, Haliloglu G, Talim B, Yau KS, Allcock RJ, Laing NG, Perrella MA, Beggs AH. SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet. 2014 Aug 7; 95(2):218-26.
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  12. Joshi M, Eagan J, Desai NK, Newton SA, Towne MC, Marinakis NS, Esteves KM, De Ferranti S, Bennett MJ, McIntyre A, Beggs AH, Berry GT, Agrawal PB. A compound heterozygous mutation in GPD1 causes hepatomegaly, steatohepatitis, and hypertriglyceridemia. Eur J Hum Genet. 2014 Oct; 22(10):1229-32.
  13. 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 Nov 28; 122(23):3845-7.
  14. Brownstein CA, Towne MC, Luquette LJ, Harris DJ, Marinakis NS, Meinecke P, Kutsche K, Campeau PM, Yu TW, Margulies DM, Agrawal PB, Beggs AH. Mutation of KCNJ8 in a patient with Cantú syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition. Eur J Med Genet. 2013 Dec; 56(12):678-82.
  15. Sankaran VG, Agrawal PB. Stimulating erythropoiesis in neonates. Am J Hematol. 2013 Nov; 88(11):930-1.
  16. Ceyhan-Birsoy 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 Oct 1; 81(14):1205-14.
  17. 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 Jun; 131(6):e1961-9.
  18. Touma M, Joshi M, Connolly MC, Grant PE, Hansen AR, Khwaja O, Berry GT, Kinney HC, Poduri A, Agrawal PB. Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings. Epilepsia. 2013 May; 54(5):e81-5.
  19. Christensen RD, Yaish HM, Leon EL, Sola-Visner MC, Agrawal PB. A de novo T73I mutation in PTPN11 in a neonate with severe and prolonged congenital thrombocytopenia and Noonan syndrome. Neonatology. 2013; 104(1):1-5.
  20. Majczenko K, Davidson AE, Camelo-Piragua S, Agrawal PB, Manfready RA, Li X, Joshi S, Xu J, Peng W, Beggs AH, Li JZ, Burmeister M, Dowling JJ. Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. Am J Hum Genet. 2012 Aug 10; 91(2):365-71.
  21. Ockeloen CW, Gilhuis HJ, Pfundt R, Kamsteeg EJ, Agrawal PB, Beggs AH, Dara Hama-Amin A, Diekstra A, Knoers NV, Lammens M, van Alfen N. Congenital myopathy caused by a novel missense mutation in the CFL2 gene. Neuromuscul Disord. 2012 Jul; 22(7):632-9.
  22. 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 May 15; 21(10):2341-56.
  23. Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari VL, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR, Beggs AH. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet. 2007 Jan; 80(1):162-7.
  24. Pierson CR, Tomczak K, Agrawal P, Moghadaszadeh B, Beggs AH. X-linked myotubular and centronuclear myopathies. J Neuropathol Exp Neurol. 2005 Jul; 64(7):555-64.
  25. PB Agrawal, AH Beggs. Multiminicore Disease. GeneReviews at GeneTests. 2005.
  26. PB Agrawal, M Singh. Neonatal Necrotizing Enterocolitis: Recent Developments. Current Issues in Pediatrics edited by N. Shendurnikar and N. Thacker. 2005.
  27. Agrawal PB, Strickland CD, Midgett C, Morales A, Newburger DE, Poulos MA, Tomczak KK, Ryan MM, Iannaccone ST, Crawford TO, Laing NG, Beggs AH. Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations. Ann Neurol. 2004 Jul; 56(1):86-96.
  28. Sethi S, Sharma M, Narang A, Aggrawal PB. Isolation Pattern and Clinical Outcome of Genital Mycoplasma in Neonates from a Tertiary Care Neonatal Unit. Journal of Tropical Pediatrics. 1999; 45:143-5.
  29. Narang A, Agrawal PB, Chakrabarti A, Kumar P. Epidemiology of systemic candidiasis in a tertiary care neonatal unit. J Trop Pediatr. 1998 Apr; 44(2):104-8.
  30. Agrawal PB, Narang A, Kumar P. Fluconazole. Indian J Pediatr. 1996 Nov-Dec; 63(6):775-80.
  31. Narang A, Agrawal P, Chakraborti A, Kumar P. Fluconazole in the management of neonatal systemic candidiasis. Indian Pediatr. 1996 Oct; 33(10):823-6.
  32. Agrawal PB, Shendurnikar N, Shastri NJ. Host factors and pneumonia in hospitalised children. J Indian Med Assoc. 1995 Jul; 93(7):271-2.
  33. Pierson CR, Agrawal PB, Blasko J, Beggs AH. Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathy. Neuromuscul Disord. 2007 Jul; 17(7):562-8.
  34. Chiu CH, Thakuria J, Agrawal PB. Novel CHD7 and FBN1 mutations in an infant with multiple congenital anamolies. Indian J Pediatr. 2010 Feb; 77(2):208-9.
  35. Leeman KT, Dobson L, Towne M, Dukhovny D, Joshi M, Stoler J, Agrawal PB. NPHP3 mutations are associated with neonatal onset multiorgan polycystic disease in two siblings. J Perinatol. 2014 May; 34(5):410-1.
  36. Brownstein CA, Beggs AH, Rodan L, Shi J, Towne MC, Pelletier R, Cao S, Rosenberg PA, Urion DK, Picker J, Tan WH, Agrawal PB. Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations. Neurogenetics. 2016 Jan; 17(1):11-6.
  37. Morton SU, Neilan EG, Peake RW, Shi J, Schmitz-Abe K, Towne M, Markianos K, Prabhu SP, Agrawal PB. Hyperammonemia as a Presenting Feature in Two Siblings with FBXL4 Variants. JIMD Rep. 2016 Nov 18.
  38. Palmer S, Towne MC, Pearl PL, Pelletier RC, Genetti CA, Shi J, Beggs AH, Agrawal PB, Brownstein CA. SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures. Pediatr Neurol. 2016 Jul 28.
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