Shilpa Hattangadi MD
Assistant Professor of Pediatrics (Hematology / Oncology) and of Pathology; Assistant Professor, Pathology
Terminal erythroid development; Hematopoiesis; Bone marrow failure; Red cell aplasia; Chromatin condensation; Nuclear protein export; Proteomics; Genomics; Transcriptional regulation; Histone modification; Post-translational modification of hematopoietic regulators
We are focused on understanding the very late stages of normal red blood cell development, from committed progenitors to circulating red blood cells (RBCs). This is important (1) to learn why certain RBC disorders develop in the first place, but also (2) to help overcome one of the challenges in the latest advancement of red blood cells grown in culture for transfusion created from patients' own hematopoietic stem cells: poor enucleation. Our most recent focus on red blood cell development has been on how enucleation is dependent on nuclear protein export, how the nucleus condenses, and how histones are replaced in the condensing red cell nucleus before it is extruded. We are also interested in identifying new genetic causes and/or modifiers of bone marrow failure syndromes and are interested in creating new mouse models of cytopenias found in children using the humanized mouse system here at Yale. We are currently pursuing one such regulator which is a post-translational modifier of hematopoietic regulators and has been found to be mutated in MDS and AML.
- SM Hattangadi, S Martinez, HC Patterson, J Shi, KA Burke, AA Figueroa, S Venkatesan, J
Wang, K Paulsen, D Gorlich, M Murata-Hori, and HF Lodish, “Histones to the cytosol: Exportin 7 is essential for normal terminal erythroid nuclear maturation”. Blood. 2014 Sep 18;124(12):1931-40. PMID: 25092175
- Shah DI, Takahashi-Makise N, Cooney JD, Li L, Schultz IJ, Pierce EL, Narla A, Seguin A,
Hattangadi SM, Medlock AE, Langer NB, Dailey TA, Hurst SN, Faccenda D, Wiwczar JM, Heggers SK, Law TC, Vogin G, Brugnara C, Zhou Y, Ebert BL, Danial NN, Fleming MD, Ward DM, Campanella M, Dailey HA, Kaplan J, and BH Paw. “Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts.” Nature. 2012 Nov 22; 491(7425):608-12. Epub 2012 Nov 7. PMID: 23135403
- Chen C, Garcia-Santos D, Ishikawa Y, Seguin A, Li L, Fegan KH, Hildick-Smith GJ, Shah DI, Cooney JD, Chen W, J. King MJ, Yien YY, Schultz IJ, Anderson H, Dalton AJ, Freedman ML, Kingsley PD, Palis J,. Hattangadi SM, Lodish HF, Ward DM, Kaplan J, Maeda T, Ponka P, and BH Paw (2013). “Snx3 regulates recycling of the transferrin receptor and iron assimilation.” Cell Metabolism. 2013 Mar 5; 17(3):343-52. Epub 2013 Feb 14. PMID: 23416069
- Hattangadi SM, Wong P, Zhang L, Flygare J, and HF Lodish (2011). From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins and RNAs (review). Blood. 2011 Dec 8; 118(24):6258-68. Epub 2011 Oct 12.
- Wong P*, Hattangadi SM*, Cheng AW, Frampton GW, Young RA, and HF Lodish (2011) Gene induction and repression during terminal erythropoiesis are mediated by distinct epigenetic changes. Blood. 2011 Oct 20; 118(16):e128-38. Epub 2011 Aug 22. *co-first authors
- Hattangadi SM, Burke KA, and HF Lodish (2010). Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation. Blood, 2010 Jun 10; 115(23) 4853-61.