dewang zhouAssistant Professor

Research Areas
Sickle cell disease and β-thalassaemia

Research Interests

Sickle cell disease and β-thalassaemia affect millions of patients worldwide and have been a global health burden for many years. The World Health Organization (WHO) estimates that 200,000 babies are born each year with SCD in Africa and that a majority will die from anemia and infections before 5 years of age. Sickle cell disease (SCD) results from a single amino acid substitution in the β-globin chain of hemoglobin (hemoglobin S), while β-thalassaemia is caused by reduced production of β-globin polypeptide due to a mutation in the β-globin gene. Both sickle cell disease and β-thalassaemia could be alleviated or even cured by up-regulation of fetal hemoglobin F(HbF). Over the years my research has demonstrated the molecular mechanisms that control the switch from HbF to HbA during human development (1, 2). Most recently I have screened a library of FDA-approved small molecule drugs and identified 2 drugs that can significantly increase fetal hemoglobin (HbF) in human CD34+-differentiated erythroid cells. The leading drug increases HbF to more than 32% of the total hemoglobin at 0.65 uM. Hydroxyurea, which is the only available drug for sickle cell patients, increases HbF to only 10% of the total hemoglobin at 10 uM. Thus, our novel leading drug is much more potent than hydroxyurea in up-regulation of fetal hemoglobin. This drug has also shown effect in upregulating fetal β-globin gene expression in human β-BAC transgenic mice. Currently we are testing its effect in pigs and monkey.

Another line of research is to develop a novel differentiation protocol that can efficiently generate a large number of authentic hematopoietic stem cells (HSC) from patient-specific induced pluripotent stem (iPS) cells. Bone marrow transplantation, mainly HSC transplantation has been the choice of treatment for hematopoietic cancers (leukemias and lymphomas), and genetic or acquired bone marrow failure, such as aplastic anemia, thalassemia, sickle cell anemia and increasingly autoimmune diseases. Transplantations of HSCs are carried out in two different settings, autologous and allogeneic. Allogeneic grafts use cells from a non-identical individual who differs in his human leukocyte antigens (HLAs), proteins that are expressed by their white blood cells. For successful transplantation, allogeneic grafts must match six to ten major HLA antigens between host and donor. Even if they do enough differences remain and cause graft-versus-host disease (GVHD). Autologous grafts use cells harvested from the patient and offer the advantage of not causing GVHD. Patient-specific iPS cells have the potential to become the novel sources of HSC.In vitro generation of HSC from iPS cells can theoretically provide an unlimited source of HSC for autologous transplantation. In combination with clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9 technology mutations in the patient-specific iPS cells can be corrected. Individual iPS clones without any off-target sequence can be identified by whole genome sequencing and used to differentiate into HSC. One of the major hurdles is the difficulty to generate enough authentic HSC for transplantation because of the extremely low differentiation efficiency of iPS cells into HSC. No current differentiation protocol is good to generate enough HSC for transplantation. It’s estimated that 2x106CD34+cells per kilogram of body weight are required in HSC transplantation. Therefore, to develop a novel differentiation protocol that can efficiently generate a large number of authentic HSC will be the key to use patient-specific iPS cells-derived therapy in clinics.

1. Dewang Zhou, Kevin M. Pawlik, Jinxiang Ren, Chiao-Wang Sun, and Tim M. Townes. (2006). Differential Binding of Erythroid Krupple-like Factor to Embryonic/Fetal Globin Gene Promoters during Development. Journal of BiologicalSciences, 281(23):16052-16057.

2. Dewang Zhou, Kaimao Liu, Chiao-Wang Sun, Kevin M. Pawlik & Tim M. Townes. (2010). KLF1 regulates BCL11A expression and γ-to β-globin gene switching. Nature Genetics, 42(9):742-744.


Graduate School
Ph.D., University of Alabama at Birmingham

Postdoctoral Fellowship
University of Alabama at Birmingham


McCallum Basic Science Building
Room 566B
1918 University Blvd.
Birmingham, AL 35294-0005

(205) 934-1963


Committed to exploring new frontiers in basic and translational research.

The Department of Biochemistry and Molecular Genetics is an integral part of the vibrant biomedical research community at the University of Alabama at Birmingham (UAB). UAB ranks among the top public institutions of higher education in terms of research and training awards. Research conducted by the faculty, staff, and students of the Department of Biochemistry and Molecular Genetics is currently supported by more than $4.3 million per year in extramural, investigator-initiated grants.


The Department of Biochemistry and Molecular Genetics carries out cutting-edge basic and translational research. Research strengths in the department includes cancer biology, chromatin and epigenetic signaling, metabolism and signaling, regulation of gene expression, structural biology, DNA synthesis and repair, and disease mechanisms.


Graduate students and postdoctoral fellows in the Department of Biochemistry and Molecular Genetics are trained to carry out hypothesis-driven research using advanced research techniques. This training will prepare our graduates for a career in not just biomedical research, but also in other diverse fields that require critical thinking. Our faculty also proudly trains professional (MD, DDS, & DO) students, as well as undergraduate students at UAB.

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