Photo of Arati Khanna-Gupta,  PhD

Arati Khanna-Gupta, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 355-9094


akhanna-gupta@partners.org

Arati Khanna-Gupta, PhD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Research Scientist, Medicine/hematology, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Over the years, research in the lab has focused on gaining an understanding of the role played by transcription factors in mediating the expression of genes that are expressed in the neutrophil maturation pathway. Previous studies from our laboratory have demonstrated defects in mRNA expression of secondary granule protein (SGP) genes and defensins in induced leukemic cell lines, in primary leukemic cells (AML), in myelodysplasia (MDS) and in a rare inherited disorder termed Specific granule deficiency (SGD). These observations supported the hypothesis that neutrophil SGP gene expression is regulated at the level of transcription. We have therefore sought to elucidate the molecular basis for SGD both to provide insight into the regulation of normal neutrophil specific gene expression and as an entry point for the study of transcriptional dysregulation in premalignant and malignant myeloid disorders.

In more recent studies, we have modeled bone marrow failure syndromes including Diamond Blackfan Anemia (DBA) and 5q- MDS in zebrafish. Haploinsufficiency of ribosomal proteins have been shown to be causitive in both these diseases. In an attempt to determine the mechanism underlying these "ribosomeopathies" we have shown that both p53 -dependent and p53-independent pathways play a role in the manifestation of the cell death and anemia associated with both diseases. Ongoing studies have begun to identify the molecular pathways affected as a result of the ribosomal stress caused by ribosomal protein haploinsufficiency.

Publications

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  • Khanna-Gupta A. Bone Marrow Failure Syndromes: The Ribosomopathies. J Bone Marrow Res 2013. PubMed
  • Khanna-Gupta A, Abayasekara N, Levine M, Sun H, Virgilio M, Nia N, Halene S, Sportoletti P, Jeong JY, Pandolfi PP, Berliner N. Up-regulation of translation eukaryotic initiation factor 4E in nucleophosmin 1 haploinsufficient cells results in changes in CCAAT enhancer-binding protein 留 activity: implications in myelodysplastic syndrome and acute myeloid leukemia. J Biol Chem 2012; 287:32728-37. PubMed
  • Payne EM, Virgilio M, Narla A, Sun H, Levine M, Paw BH, Berliner N, Look AT, Ebert BL, Khanna-Gupta A. L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway. Blood 2012; 120:2214-24. PubMed
  • Dutt S, Narla A, Lin K, Mullally A, Abayasekara N, Megerdichian C, Wilson FH, Currie T, Khanna-Gupta A, Berliner N, Kutok JL, Ebert BL. Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 2011; 117:2567-76. PubMed
  • Khanna-Gupta A. Regulation and deregulation of mRNA translation during myeloid maturation. Exp Hematol 2011; 39:133-41. PubMed
  • Halene S, Gaines P, Sun H, Zibello T, Lin S, Khanna-Gupta A, Williams SC, Perkins A, Krause D, Berliner N. C/EBPepsilon directs granulocytic-vs-monocytic lineage determination and confers chemotactic function via Hlx. Exp Hematol 2010; 38:90-103. PubMed
  • Khanna-Gupta A, Chen J, Sliver M. Sun H, Abayasekara N, Halene, S, Spotoloetti P, Pandlofi PP, Berliner N.. Nucleophosmin-1 interacts with CCAAT enhancer binding protein alpha (C/EBPalpha) to facilitate granulocyte maturation: implications in MDS and AML Blood 2009.