Nov 11, 2022
RPG Seminar (2022-11-11)
Date: Friday, 11 November 2022
Time: 5:00 p.m. - 6:00 p.m.
Venue: Cheung Kung Hai Lecture Theatre 2, G/F, William M.W. Mong Block, 21 Sassoon Road
Presenter: Miss Shiya YU, PhD candidate
Primary Supervisor: Dr. You-qiang SONG
Presentation Title: Differentiation and migration of CD34+ cells across tissues during hematopoiesis revealed by single cell analyses
Abstract: Bone marrow CD34+ cells, which represent hematopoietic stem and progenitor cells (HSPCs), are commonly used for investigating hematopoiesis. However, the relationships between CD34+ cells from different tissues remain largely elusive. Here, we analyzed the single-cell RNA-seq data of human CD34+ cells in bone marrow, peripheral blood, and thymus, to investigate their dynamics across tissues. Integrative analysis of these CD34+ cells identified major cell populations and established the hematopoietic lineages during early hematopoiesis. Interestingly, we found most hematopoietic stem cell subsets in bone marrow except B cell lineages have counterparts in peripheral blood. However, we only found the counterparts of earliest thymic progenitor cells in peripheral blood, while did not find their counterparts for the other thymic CD34+ cells in bone marrow and peripheral blood. Together, these data showed there is a single unified developmental spectrum for hematopoiesis in different tissues, with cell migration playing an important role in hematopoiesis.
Presenter: Mr. Jason Ying Ki LI, MPhil candidate
Primary Supervisor: Dr. Clive CHUNG
Presentation Title: Covalent ligand targeting RhoA GTPase in cancer treatment
Abstract: RhoA GTPase has been reported as a driver in different human cancers, however, conventional drug design remains unsuccessful due to its lack of deep binding pocket and nanomolar range affinity to its substrate GTP. We have performed covalent ligand screening using activity-based protein profiling (ABPP) to identify a covalent RhoA inhibitor 1F2. LC-MS/MS experiment revealed compound binding at Cys16 which is a novel binding site near the GTP-binding pocket. Cytotoxicity in CRC was found to show good correlations with expression level of RhoA in these cancer cells, indicating high specificity of 1F2 to mediate anti-cancer effects through RhoA inhibition. We also showed 1F2 treatment caused significant shrinkage in CRC spheroid and deceleration in xenograft growth with no observable toxicity. Our results uncovered a novel RhoA covalent inhibitor with promising anti-cancer and anti-metastatic effects.
ALL ARE WELCOME
Should you have any enquiries, please feel free to contact Miss Cynthia Cheung at 3917 9748.