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.
Hattangadi SM, Martinez-Morilla S, Patterson HC, Shi J, Burke K, Avila-Figueroa A, Venkatesan S, Wang J, Paulsen K, Görlich D, Murata-Hori M, Lodish HF. Histones to the cytosol: exportin 7 is essential for normal terminal erythroid nuclear maturation. Blood 2014, 124:1931-40.
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, Vogin G, Chen W, Chen C, Campagna DR, Brugnara C, Zhou Y, Ebert BL, Danial NN, Fleming MD, Ward DM, Campanella M, Dailey HA, Kaplan J, Paw BH. Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts. Nature 2012, 491:608-12.
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, 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, Paw BH. Snx3 regulates recycling of the transferrin receptor and iron assimilation. Cell Metabolism 2013, 17:343-52.
From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications.
Hattangadi SM, Wong P, Zhang L, Flygare J, Lodish HF. From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications. Blood 2011, 118:6258-68.
Full List of PubMed Publications
- Avila Figueroa A, Fasano JD, Martinez-Morilla S, Venkatesan S, Kupfer G, Hattangadi SM: miR-181a regulates erythroid enucleation via the regulation of Xpo7 expression. Haematologica. 2018 Mar 22; 2018 Mar 22. PMID: 29567782