joe sunAssistant Professor

Research Areas
Sickle cell disease


Research Interests

Sickle cell disease (SCD) is the first human inherited diseases that understand at molecular level. Sickle cell anemia is a monogenic hemoglobinopathy wherein glutamic acid, the sixth amino acid in the β-globin chain, is displaced by valine. This results in hemoglobin polymerization and sickling morphology during hemoglobin desaturation. Clinically, the disease is characterized by chronic hemolysis, intermittent vaso-occlusive events, and organ injury. Approximately 70,000-100,000 Americans have sickle cell anemia in U.S., about 1 in 365 black children is born with SCD. Correction of the sickle mutation in autologous hematopoietic stem/progenitor cells would provide a therapy available to all patients.

We have produced a humanize mouse model of SCD that provides a tool to gain insight into the therapeutic applicability in SCD. To correct the sickle mutation, we have utilized and modified the CRISPR/Cas system to correct the SCD genetic defect in our animal model and done the secondary transplant to prove in correction the sickle mutation in long-term hematopoietic stem cells. In addition, we have adapted the modified CRISPR/Cas system in correcting the mutation for patient-specific induced Pluripotent Stem Cells (iPSCs), and CD34 cells purified from patients’ peripheral blood or bone marrow cells with good efficient and very low indel. The new modified CRISPR/Cas not only enhanced correction of SCD but also reduced off-target modifications. The final goal is autologous transplant the corrected stem/progenitor or red blood cells (RBC) derived from corrected patient specify iPSCs, or corrected CD34 cells back to patient to cure the disease.

We have also extended our study in cancer biology under sickle cell environments. Results showed that sickle cells but not normal RBCs possess a unique ability to home to hypoxic tumor cell niches, form micro aggregates that shut down tumor blood flow and induce a tumoricidal response. These studies unveiled several checkpoints in the sickle cell-mediated thrombo-inflammatory pathway for synergy with selected anti-tumor agents. In combination of sickle cell-drugs platform to treat hypoxic niches in human lung carcinoma and melanoma cancers with new strategy in cancer therapy.

Education

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

Contact

Office
Kaul Human Genetics Building
Room 520
720 20th Street South
Birmingham, AL 35294-0024

Phone
(205) 934-1963

Email
jsun@uab.edu

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.

Research

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.

Education

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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