CURRENT CLINICAL INTERESTS
General hematology; myelodysplastic syndrome (MDS); myeloproliferative disorders, and especially polycythemia vera and essential thrombocytosis; pure red cell aplasia, aplastic anemia and other marrow failure syndromes.
CURRENT RESEARCH INTERESTS
Research in hematopoietic stem cells, erythropoiesis, heme and iron physiology, marrow failure, myelodysplastic syndrome (MDS).
The major focus of Dr. Abkowitzs research is understanding the molecular and cellular events that control red cell differentiation. Given her recent observation that the severe macrocytic anemias of Diamond Blackfan anemia (DBA) and myelodysplastic syndrome with an isolated deletion of chromosome 5q (del(5q) MDS) result from insufficient ribosome numbers or function, a slowed initiation of globin synthesis, excessive heme and heme toxicity (Science Translational Medicine, 2016), her lab is especially interested in understanding how the poor coordination of heme with globin might lead to ineffective erythropoiesis more broadly. As examples, she is investigating heme signaling and the molecular consequences of excess heme with single cell RNA seq studies of murine models and MDS patient morrow samples. She (with Bart Scott MD) is also initiating a clinical trial of aggressive chelation in persons with MDS and anemia.
Dr. Abkowitz's other research interest is understanding hematopoietic stem cell (HSC) kinetics, in part by the mathematical modeling of cell fate-decisions using stochastic methods (a collaboration with Vladimir Menon PhD, Professor of Statistics, University of Washington). This work allows insights into HSC differentiation during normal hematopoiesis, the pathophysiology of aplastic anemia, and the clonal evolution and progression of myeloproliferative disorders.
Abkowitz JL, Catlin SN, Guttorp P: Evidence that hematopoiesis may be stochastic in vivo. Nature Medicine 2:190-197, 1996. PMID: 8574964.
Abkowitz JL, Taboada M, Shelton GH, Catlin SN, Guttorp P and Kiklevich JV. An X-chromosome gene regulates hematopoietic stem cell kinetics. Proc. Natl. Acad. Sci. USA 95:3862-3866, 1998. PMID: 9520458.
Quigley JG, Yang Z, Worthington MT, Phillips JD, Sabo KM, Sabath DE, Berg CL, Sassa S, Wood BL, Abkowitz JL: Identification of a human heme exporter that is essential for erythropoiesis. Cell 118:757-66, 2004
J, Larochelle A, Fricker S, Bridger G,
CE, Abkowitz JL: Mobilization as a preparative regimen
for hematopoietic stem cell transplantation. Blood
107:3764-3771, 2006. PMID: 16439683.
Abkowitz JL, Chen J. Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones. Blood 109:5186-5190, 2007. PMID: 17347409. PMCID: PMC1890826.
Keel SB, Doty RT, Yang Z, Quigley JG, Chen J,
Kingsley PD, De Domenico I, Vaughn MB,
Kaplan J, Palis J, Abkowitz JL:
A heme export protein is required for red blood cell differentiation
and iron homeostasis. Science 319:825-828, 2008
Catlin SN, Busque L, Gale R, Guttorp P and Abkowitz JL The replication rate of human hematopoietic stem cells in vivo. Blood 117:4460-4466, 2011. PMID: 21343613; PMCID: PMC3099568.
Philip M, Funkhouser SA, Chiu EY, Phelps SR, Delrow JJ, Cox J, Fink PJ, and Abkowitz JL. Heme exporter FLVCR is required for T cell development and peripheral survival. J Immunol 194:1677-85, 2015. PMID: 25582857; PMCID: PMC4323866.
Doty RT, Phelps SR, Shadle C, Sanchez-Bonilla M, Keel SB, and Abkowitz JL. Coordinate expression of heme and globin is essential for effective erythropoiesis. J Clin. Invest. 125:4681-91, 2015. PMID: 26551679.
Yang Z, Keel SB, Shimamura A, Liu L, Gerds AT, Li HY, Wood BL, Scott BL, and Abkowitz JL. Delayed globin synthesis leads to excessive heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome. Science Transl. Med. 8:338RA67, 2016. PMID: 27169803.