Biology

Biology

Spotlight on Student Research

Michelle Mojadidi

Michelle Mojadidi defended her Master’s Degree Thesis under the guidance of Dr. Cindy Malone, performing her Graduate research in the CSUN-UCLA Bridges to Stem Cell Research Program in the laboratory of Dr. Don Kohn, MD. Michelle studied Sickle Cell Disease (SCD), a blood disorder characterized by defective hemoglobin (HbS) due to a point mutation in the β-globin chain. This mutation causes the red blood cells to sickle under low oxygen conditions and these misshapen blood cells present a danger because they have a tendency to clump together and block small vessels. The β-like chain (Hb) is expressed throughout ontogeny from different genes, with the switching from fetal hemoglobin (HbF) to adult hemoglobin (HbA) during the first 6 months after birth. If this switch is incomplete, high levels of HbF in adults causes a milder clinical manifestation of SCD than adult SCD. If the fetal HB in SCD patients can be increased, their symptoms of SCD can be decreased for a better quality of life. Michelle’s project centers around the proof of principle of manipulating stem cells to persist in expressing HbF by disrupting a known transcriptional repressor, BCL11A. Knockdown of BCL11A using precise artificially engineered nucleases, for example, zinc finger nucleases (ZFNs), transcription activator like nucleases (TALENs) and clustered regulatory interspaced short palindromic repeats (CRISPRs) is an attractive strategy to reactivate HbF and restore mostly functional erythrocytes in patients suffering from SCD. Michelle’s results indicate that ZFN are efficient in human stem cells for genome engineering to knockdown BCL11A and increase persistence of HbF in stem cells compared to TALENs and CRISPR/Cas9.  Michelle is currently employed as a Lab Manager/Research Technician at UCLA, awaiting news from Medical school waitlists.