Disease Models, Animal; Erythropoiesis; Hematologic Diseases; Hematopoiesis; Heterochromatin; Histone Deacetylases; Histones; Microscopy, Confocal; Nucleocytoplasmic Transport Proteins; Chromatin Immunoprecipitation; Erythroid-Specific DNA-Binding Factors
Public Health Interests
Cancer; Cancer genetics; Child health; Chronic disease management; Data analysis; Genomics
We are focused on understanding the terminal stages of normal red blood cell development, from terminally 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 challenges in treatment of these disorders as well as develop new ones. 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.
Histones to the cytosol: Exportin 7 is essential for normal terminal erythroid nuclear maturation.
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. Blood. 2014 Sep 18;124(12):1931-40. PMID: 25092175
Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts.
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. Nature. 2012 Nov 22; 491(7425):608-12. Epub 2012 Nov 7. PMID: 23135403
Snx3 regulates recycling of the transferrin receptor and iron assimilation.
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). Cell Metab. 2013 Mar 5;17(3):343-52. Epub 2013 Feb 14. PMID: 23416069
From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins and RNAs (review).
Hattangadi SM, Wong P, Zhang L, Flygare J, and HF Lodish (2011). Blood. 2011 Dec 8; 118(24):6258-68. Epub 2011 Oct 12. PMID: 21998215
Gene induction and repression during terminal erythropoiesis are mediated by distinct epigenetic changes.
Wong P*, Hattangadi SM*, Cheng AW, Frampton GW, Young RA, and HF Lodish (2011). Blood. 2011 Oct 20;118(16):e128-38. Epub 2011 Aug 22. PMID: 21860024
Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.
Hattangadi SM, Burke KA, and HF Lodish (2010). Blood, 2010 Jun 10; 115(23) 4853-61. Epub 2010 Mar 15. PMID: 20231426
Regulation of erythrocyte lifespan: do reactive oxygen species set the clock?
Hattangadi SM, Lodish HF. J Clin Invest. 2007 Aug;117(8):2075-7. PMID: 17671642