Section of Hematology / Oncology
Professor of Medicine
Director, Clinical Cell Therapy Laboratory;Director, cGMP Cellular Manufacturing Core Facility
|PhD||1989||Miami University||Chemistry and Biochemistry
Dr. Wickrema's work is focused on the study of normal and malignant hematopoiesis. His laboratory's work over the years has entailed studying the signaling pathways underlying lineage commitment and terminal differentiation of adult blood/bone marrow stem cells into erythroid cells. A human in vitro primary cell culture model developed by his group has been pivotal in efforts towards understanding the signal transduction pathways and molecular mechanisms that regulate cell survival, proliferation and differentiation into mature red blood cells. These efforts have identified the key pathways as well as cytokines that regulate the overall red blood cell production. His group has active collaborations with multiple research groups both at University of Chicago and around the country.
Current work include projects that are focused on understanding the precise functional and prognostic implications of specific mutations as seen in myelodysplastic syndromes (MDS), a group of malignant blood disorders . These studies include designing novel strategies for therapeutic intervention using the knowledge gained by the DNA sequence information publicly available to the scientific community. A second line of investigation focuses on understanding the epigenetic signals that permit lineage commitment of blood/morrow stem cells and molecular mechanisms underlying terminal events in human erythroid differentiation program. This includes studying the biological pathways that permit the extrusion of the nucleus, which is exclusive to most mammalian red blood cells. A third line of investigation focuses on developing methods for using blood stem cells and partially differentiated blood cells for treatment of anemia and other blood disorders as cell replacement therapies. A key goal of this research is to devise strategies that will lead to creation of low cost high value cellular therapy products.
- Sundaravel S, Duggan R, Bhagat T, Ebenezer DL, Liu H, Yu Y, Bartenstein M, Unnikrishnan M, Karmakar S, Liu TC, Torregroza I, Quenon T, Anastasi J, McGraw KL, Pellagatti A, Boultwood J, Yajnik V, Artz A, Le Beau MM, Steidl U, List AF, Evans T, Verma A, Wickrema A. Reduced DOCK4 expression leads to erythroid dysplasia in myelodysplastic syndromes. Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6359-68.
- Zhao B, Mei Y, Schipma MJ, Roth EW, Bleher R, Rappoport JZ, Wickrema A, Yang J, Ji P. Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening.Dev Cell. 2016 Mar 7;36(5):498-510
- Geslain R+, Uddin S+, Liu H, Zhou Y, Ulaszek J, van Besien K, Pan T, Wickrema A (2013): Distinct functions of erythropoietin and stem cell factor are linked to activation of mTOR Kinase signaling pathway in human erythroblasts. Cytokine, 61: 329-335.
- Keerthivasan G, Small S, Liu H, Wickrema A, Crispino JD (2011): Vesicle trafficking plays a novel role in erythroblast enucleation. Blood. 116: 3331-3340.
- Madzo, J., Liu, H., Rodriguez, A., Vasanthakumar, A., Sundaravel, S., Caces, D.B., Looney, T.J., Zhang, L., Lepore, J.B., Macrae, T., Duszynski, R., Shih, A.H., Song, C.X., Yu, M., Yu, Y., Grossman, R., Raumann, B., Verma, A., He, C., Levine, R.L., Lavelle, D., Lahn, B.T., Wickrema, A*., and Godley, L.A* (2014). Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis. Cell Rep. 6: 231-44 (2014).
* Corresponding senior authors