Associate Professor

Research Areas
Sickle cell disease

Research Interests

My research interests are part of a broader effort by the Townes lab to cure sickle cell disease (SCD) using gene/cell therapy approaches. For proof-of-concept studies, we (Ryan, Pawlik and Townes) developed a mouse model for SCD in which we knocked out the mouse alpha-and beta-globin genes and replaced them with human alpha-and gamma-beta A/S-globin genes; we and others have subsequently cured these mice using various approaches and they continue to be widely used in the field (available from The Jackson Laboratory, Stock No: 013071, Townes model). We (Pawlik and Townes) also developed a polycistronic lentiviral vector for "hit and run" reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) in order to modifygenes in pluripotent cells and then differentiate them into cell types of interest (available from Addgene, ID 21627, pKP332, hOCT4-2A-hSOX2-2A-hKLF4).

In current studies, CD34-positive hematopoietic stem cells (HSCs) are isolated from human SCD (HBB SS) patient blood; the disease-causing T nucleotide mutation (valine aa) is corrected to the wild-type A nucleotide (glutamic acid aa) using CRISPR/Cas9-enhanced gene targeting; and corrected HSCs are introduced into murine recipients via bone marrow transplantation (BMT) to effect production of wild-type HBB AA and/or trait HBB AS cell progeny. Additionally, we have used a CRISPR/Cas9-based approach in Severe Combined Immunodeficiency (SCID) patient-derived iPSCs to correct the disease-causing JAK3 C > T nucleotide substitution. My interests also include methodologies to determine CRISPR/Cas9 off-targets in order to minimize unintended genome modifications.

Education

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

Contact

Office
Shelby Biomedical Research Building
Room 702
1825 University Blvd.
Birmingham, AL 35294-2182

Phone
(205) 410-6861

Email
kpawlik@uab.edu