ABOUT THE RESEARCHER

OVERVIEW

Dr. Majmundar is currently an attending pediatric nephrologist at Boston Children's Hospital and an instructor of pediatrics at Harvard Medical School. Dr. Majmundar's research explores the genetic basis of pediatric kidney diseases with a focus on Mendelian genetic forms of nephrotic syndrome and kidney stone disease.

Active projects in his laboratory include discovering novel Mendelian genetic causes of pediatric kidney stone diseases using human genomics, (ii) investigating the biological mechanisms by which recessive genetic variants in NOS1AP cause a pediatric glomerulopathy via cellular and mouse models, and (iii) dissecting the biological mechanisms by which de novo variants in TRIM8 cause a syndrome of epilepsy and nephrotic syndrome in humans using cellular and mouse models.

Laboratory Personnel:

Amar Majmundar, MD PhD (principal investigator)
Vineeta Sharma, PhD (post-doctoral fellow)
David Ball, BS (research assistant)
Lorrin Liang, BS (master's thesis student)

BACKGROUND

Dr. Majmundar began his medical and graduate training in the Combined Degree and Medical Scientist Training Programs at the University of Pennsylvania School of Medicine (2004-2013). There, he earned a PhD in Cell and Molecular Biology in the laboratory of M. Celeste Simon PhD. During his thesis research, he discovered that the oxygen sensing factor Hif1α specifically regulates adult skeletal muscle regeneration, but not embryonic muscle development, by inhibiting WNT signaling. For these studies, he generated and evaluated three mouse models and employed primary and immortalized muscle progenitor culture. His thesis research led to publications in Development, Molecular and Cellular Biology, Molecular Cell, The Journal of Clinical Investigation and Proceedings of the National Academy of Sciences.

He, subsequently, completed pediatrics training in the Boston Combined Pediatrics Residency program at Boston Children’s Hospital and Boston Medical Center followed by pediatric nephrology fellowship training at Boston Children’s Hospital. He conducted post-doctoral fellowship research with Dr. Friedhelm Hildebrandt and discovered novel monogenic causes of steroid-resistant nephrotic syndrome/focal segmental glomerulosclerosis (SRNS/FSGS) in human NOS1AP and TRIM8 mutations using exome sequencing approaches. He investigated the pathogenesis of these human mutations using cell-based assays and mouse models. He further explored the Mendelian genetic landscape of pediatric and adult nephrolithiasis using gene panel and exome sequencing techniques. In the process, he determined that dominant OXGR1 variants are a potentially novel cause of nephrolithiasis. His findings have led to four first-authored research articles (Science Advances, American Journal of Human Genetics, Kidney International, Human Genetics) and 23 co-authored publications.

His research during fellowship and, now, as faculty have been supported by the NIH National Institute of Diabetes and Digestive and Kidney Diseases, NIH National Institute of Child Health and Human Development, the American Society of Nephrology, the Polycystic Kidney Disease Foundation, the Harvard Stem Cell Institute, and the Boston Children's Hospital Manton Center for Orphan Disease Research.

PUBLICATIONS

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  1. Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT. Genet Med. 2021 Nov 16. View abstract
  2. Sequencing the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant atypically associated with nephrolithiasis. BMC Med Genomics. 2021 11 12; 14(1):266. View abstract
  3. Cystin genetic variants cause autosomal recessive polycystic kidney disease associated with altered Myc expression. Sci Rep. 2021 09 14; 11(1):18274. View abstract
  4. Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat Syndrome. J Am Soc Nephrol. 2021 03; 32(3):580-596. View abstract
  5. A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features. Genet Med. 2021 06; 23(6):1158-1162. View abstract
  6. De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis. Am J Hum Genet. 2021 02 04; 108(2):357-367. View abstract
  7. Mutations in transcription factor CP2-like 1 may cause a novel syndrome with distal renal tubulopathy in humans. Nephrol Dial Transplant. 2021 01 25; 36(2):237-246. View abstract
  8. Recessive NOS1AP variants impair actin remodeling and cause glomerulopathy in humans and mice. Sci Adv. 2021 Jan; 7(1). View abstract
  9. Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches. Kidney Int Rep. 2021 Feb; 6(2):460-471. View abstract
  10. DAAM2 Variants Cause Nephrotic Syndrome via Actin Dysregulation. Am J Hum Genet. 2020 12 03; 107(6):1113-1128. View abstract
  11. Recessive Mutations in SYNPO2 as a Candidate of Monogenic Nephrotic Syndrome. Kidney Int Rep. 2021 Feb; 6(2):472-483. View abstract
  12. Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations. Am J Hum Genet. 2020 10 01; 107(4):727-742. View abstract
  13. CAKUT and Autonomic Dysfunction Caused by Acetylcholine Receptor Mutations. Am J Hum Genet. 2019 12 05; 105(6):1286-1293. View abstract
  14. Whole exome sequencing identified ATP6V1C2 as a novel candidate gene for recessive distal renal tubular acidosis. Kidney Int. 2020 03; 97(3):567-579. View abstract
  15. Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies. Pediatr Rheumatol Online J. 2019 Jul 30; 17(1):52. View abstract
  16. Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome. Kidney Int. 2019 10; 96(4):883-889. View abstract
  17. COL4A1 mutations as a potential novel cause of autosomal dominant CAKUT in humans. Hum Genet. 2019 Oct; 138(10):1105-1115. View abstract
  18. Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout. Kidney Int. 2019 05; 95(5):1079-1090. View abstract
  19. Genetic variants in the LAMA5 gene in pediatric nephrotic syndrome. Nephrol Dial Transplant. 2019 03 01; 34(3):485-493. View abstract
  20. Panel sequencing distinguishes monogenic forms of nephritis from nephrosis in children. Nephrol Dial Transplant. 2019 03 01; 34(3):474-485. View abstract
  21. Gene panel sequencing identifies a likely monogenic cause in 7% of 235 Pakistani families with nephrolithiasis. Hum Genet. 2019 Mar; 138(3):211-219. View abstract
  22. Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients. J Am Soc Nephrol. 2019 02; 30(2):201-215. View abstract
  23. Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome. J Clin Invest. 2018 10 01; 128(10):4313-4328. View abstract
  24. Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract. J Am Soc Nephrol. 2018 09; 29(9):2348-2361. View abstract
  25. Mutations in WDR4 as a new cause of Galloway-Mowat syndrome. . 2018 11; 176(11):2460-2465. View abstract
  26. GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome. J Am Soc Nephrol. 2018 08; 29(8):2123-2138. View abstract
  27. Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment. Nat Commun. 2018 05 17; 9(1):1960. View abstract
  28. Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model. PLoS One. 2018; 13(1):e0191503. View abstract
  29. Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome. Clin J Am Soc Nephrol. 2018 01 06; 13(1):53-62. View abstract
  30. Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int. 2018 01; 93(1):204-213. View abstract
  31. HIF modulation of Wnt signaling regulates skeletal myogenesis in vivo. Development. 2015 Jul 15; 142(14):2405-12. View abstract
  32. Endothelial HIF-2a regulates murine pathological angiogenesis and revascularization processes. J Clin Invest. 2012 Apr; 122(4):1427-43. View abstract
  33. O(2) regulates skeletal muscle progenitor differentiation through phosphatidylinositol 3-kinase/AKT signaling. Mol Cell Biol. 2012 Jan; 32(1):36-49. View abstract
  34. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010 Oct 22; 40(2):294-309. View abstract
  35. Hemodynamic and metabolic diffuse optical monitoring in a mouse model of hindlimb ischemia. Biomed Opt Express. 2010 Oct 15; 1(4):1173-1187. View abstract
  36. HIF2alpha inhibition promotes p53 pathway activity, tumor cell death, and radiation responses. Proc Natl Acad Sci U S A. 2009 Aug 25; 106(34):14391-6. View abstract
  37. Epigenetic downregulation of the DNA repair gene MED1/MBD4 in colorectal and ovarian cancer. Cancer Biol Ther. 2009 Jan; 8(1):94-100. View abstract
  38. Combined millimeter wave and cyclophosphamide therapy of an experimental murine melanoma. Bioelectromagnetics. 2004 Oct; 25(7):516-23. View abstract