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May 07 - 28, 2021

RPG Seminar Series (May 2021)

Date: Friday, 7 May 2021

Venue: Cheung Kung Hai Lecture Theatre 1, G/F, William M.W. Mong Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

Time: 5:00 p.m. - 6:00 p.m.

5:00 p.m.

Speaker: Miss Xiunan FANG (PhD candidate)
Primary Supervisor: Dr. Joshua Wing Kei HO
Presentation Title: Scalable single cell analysis
Abstract: Single-cell RNA sequencing (scRNA-seq) is powerful for unravelling the individual cellular transcriptomic profile of a population of cells and has enabled profound insight into transcriptomics analysis. Recent technological advances enable tens of thousands of single cells to be routinely profiled in an experiment. The number of reported cells in each single cell study increased from several hundreds to several millions during these years. The increasing scale of scRNA-seq analysis urges the need for a scalable and reliable analysis tools and pipelines that can handle single cell data sets on the scale of millions. By taking advantage of large-scale single cell data analytics, there will be greater potential for biological and medical research.

5:30 p.m. 

Speaker: Miss Wing Lam CHAN (MPhil candidate)
Primary Supervisor: Dr. Martin Chi Hang CHEUNG
Presentation Title: Study of Hirschsprung disease associated ephrinA1 mutation in enteric neural crest cells
Abstract: During enteric neural crest cell (ENCC) colonization, cell-cell interaction drives ENCCs migration and differentiation. Eph/ephrin signaling is known to regulate cell migration and segregation in neural development. However, its role in ENCC development remains unknown. Previous study reported mutations of EphA5, EphB2 and ephrinA1 genes in patients with Hirschsprung disease caused by defects in ENCC colonization. Therefore we hypothesize that Eph and ephrin may play an important role in mediating ENCC migration, and their mutations may lead to defects in cell-cell interaction. The impact of mutation in ephrinA1 on cell-cell interaction is examined by co-culture assay. Our results demonstrated abnormal segregation of HEK293 cells stably expressing mutated ephrinA1 from EphA4 expressing cells compared with ephrinA1/EphA4 co-culture. In summary, the study will provide better understanding on the role of Eph/ephrin signaling in ENCC migration and pathogenesis of Hirschsprung disease.

Date: Friday, 14 May 2021

Venue: Seminar Room 1-3, G/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

Time: 5:00 p.m. - 6:00 p.m.

5:00 p.m.

Speaker: Mr. Bo ZHOU (PhD candidate)
Primary Supervisor: Dr. You-qiang SONG
Presentation Title: Investigation of developmental functional properties of neutrophils using single cell RNA sequencing
Abstract: Neutrophils are a type of leukocytes and play pivotal roles in immune response. It is well known that neutrophils developed in bone marrow, however, the detailed developmental process and regulatory elements of neutrophils still not well understood. In this study, we profiled gene expression of about 108k single cells, including about 55k neutrophils, from bone marrow and peripheral blood of mice. We characterized neutrophil trajectory, and revealed their transcriptional signatures of each subset during developmental progress. We then inferred cellular signaling communication network and it is suggested neutrophil subsets along developmental stages were involved in different pathways. Besides, we analyzed neutrophil production at single cell resolution under different conditions, including aging, bacterial infection, and leukemia progression. Overall, these results significantly increased our understanding of transcriptional dynamics of neutrophil lineage.

5:30 p.m. 

Speaker: Mr. Umar Farook Asif Iqbal PATEL (PhD candidate)
Primary Supervisor: Dr. Martin Chi Hang CHEUNG
Presentation Title: Identification and characterisation of drug resistant melanoma stem cells
Abstract: Cutaneous melanoma is over-represented among skin cancer mortalities due to frequent development of metastasis and drug resistance. BRAF and MEK kinase inhibition, the primary therapeutic choice for late-stage metastasis, is effective in the short term but is often accompanied by tumour recurrence in the long term, implying an incomplete therapeutic response thought to be driven in part by melanoma stem cells.

We have identified a rare subpopulation of melanoma cells expressing OCT4-promoter-driven GFP upon BRAF/MEK-inhibition. These GFP+ melanoma cells express high levels of embryonic and melanoma stem cell markers and drug resistance markers compared to the GFP- bulk melanoma cell population.

We hypothesise that this rare population of GFP+ melanoma cells may acquire stemness properties with a transcriptional program distinct from the bulk tumour mass. If so, molecular characterisation of this subpopulation may allow for the identification of novel therapeutic targets that govern melanoma stemness and therapy resistance.

Date: Friday, 21 May 2021

Venue: Cheung Kung Hai Lecture Theatre 1, G/F, William M.W. Mong Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

Time: 5:00 p.m. - 6:00 p.m.

5:00 p.m.

Speaker: Miss Ziwei HE (MPhil candidate)
Primary Supervisor: Prof. Pengtao LIU
Presentation Title: From mESCs to mEPSCs: A proteomics-based study
Abstract: The mouse expanded potential stem cells (mEPSCs) are able to contribute to both embryonic and extra-embryonic tissues. They can be derived from preimplantation embryos, or converted from mouse embryonic stem cells (mESCs) which normally only has the capacity to give rise to the embryonic cell lineages. This mESC-to-mEPSC transition is achieved by culturing mESCs in the mEPSCs medium which contains several small molecule inhibitors targeting key signaling pathways in development. Among them is XAV939, a Tankyrase inhibitor. It has been known that Tankyrase inhibition by XAV939 stabilizes Axin1, which is a negative regulator of canonical Wnt signaling and promotes β-catenin degradation. Notably, the increased protein level of Axin1 is verified in mEPSCs. Genetic overexpression of Axin can also efficiently convert mESCs to EPSCs, validated by the chimera experiment. Here, to uncover the underlying molecular mechanism of Axin1 in the mESCs-mEPSCs transition, I established a transgenic mouse ES cell line with inducible Axin1 overexpression. By performing Affinity Purification combined with Mass Spectrometry analysis, we aim to identify Axin1-interacting proteins and investigate their functional significance in the mESCs to mEPSCs transition process.

5:30 p.m. 

Speaker: Miss Mengxia ZHU (PhD candidate)
Primary Supervisor: Prof. Danny CHAN
Presentation Title: Universal allogenic and FailSafe nucleus pulposus progenitor cells for intervertebral disc regeneration
Abstract: Intervertebral disc degeneration (IDD) causes back pain affecting quality of life. Currently, there are no effective biological treatments. The nucleus pulposus (NP) is at the core of the intervertebral disc (IVD), and its cellular content is key to a healthy disc. Notochordal-like cells (NLCs) in the NP serve as progenitors that differentiate to NP cells for IVD function. In human, a decline in NLC content and differentiation of NP cells to fibrotic cells coincides with the onset and severity of IDD. A potential cellular-based therapy for IDD consists of NLCs derived from stem cells such as human induced pluripotent stem (iPS) or embryonic stem (ES) cells. Here, we use a genetically engineered “immuno-cloaked and FailSafe” system, where these cells will evade the host immune system, and if they become tumorigenic, be eliminated. In vitro differentiated NLCs will be created, tagged with fluorescent proteins marking specific NLC proteins (TBXT and TAGLN). Their efficiency and efficacy to sustain long-term repair of a degenerating IVD in humanized mice will be assessed.

Date: Friday, 28 May 2021

Venue: Cheung Kung Hai Lecture Theatre 1, G/F, William M.W. Mong Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

Time: 5:00 p.m. - 6:00 p.m.

5:00 p.m.

Speaker: Miss Ya GAO (PhD candidate)
Primary Supervisor: Dr. Ralf JAUCH
Presentation Title: Directed evolution of enhanced Krüppel-like transcription factors for cell fate engineering
Abstract: Our group has previously established a novel strategy for the directed molecular evolution in mammalian cells to engineer cell fate decisions with the help of improved transcription factors for pluripotency and neural reprogramming. Using this method, we have identified and characterized several enhanced transcription factors (eTFs) based on the scaffolds of POU and SOX proteins (ePOU and eSOX). Here we apply our protein and cell fate engineering paradigm to the Krüppel-like factor 4 (KLF4) transcription factor for its essential roles in pluripotency induction and neural transdifferentiation. KLF4 contains three C2H2 zinc fingers at its carboxyl terminus conferring sequence specific binding to GC-rich DNA motifs. KLF4 is a pioneer factor that binds nucleosomal DNA as well as methylated CpG elements. To improve its capacity to direct cell fate transitions, we rationally designed three saturation mutagenesis eKLF4 libraries. Using pooled screens in mouse pluripotency reprogramming, we identified several evolved KLF4 (eKLF4) variants that outperform wild-type KLF4. Intriguingly, most variants with high performance cluster at structural positions critical for the recognition of epigenetically modified DNA.  Further investigations are being carried out in human pluripotency reprogramming and neural transdifferentiation. The study of the chromatin binding and gene regulation of eKLF4 compared to KLF4 will help to elucidate the molecular basis for pioneer factor function, decode its sequence-structure-function relationship and inform the functional enhancements of KLFs to optimize strategies for the generation of functional cell types for regenerative medicine.

5:30 p.m. 

Speaker: Mr. Weizhong ZHENG (PhD candidate)
Primary Supervisor: Dr. Joshua Wing Kei HO
Presentation Title: Multi-task learning for modeling translational efficiency of mRNA based on its 5’UTR sequence content’
Abstract: The translation process from mRNA to protein is heavily regulated by the 5’ untranslated region (5’ UTR). Although various regulatory elements in 5’ UTR have been identified, it is still challenging to accurately predict the translation efficiency (TE) for mammalian mRNA sequences. We propose a multi-task learning solution that can perform TE-prediction, sequence reconstruction, and motif detection at a single run. Utilizing information shared between tasks, our model demonstrates a higher prediction accuracy than the single-task model and it can also generate novel 5’ UTR sequences of specific TE-score. By transferring our model to other datasets, our next step aims to tailor the model to different cell types or organisms, to broaden its potential application in biological research.

All are welcome. 

Should you have any enquiries, please feel free to contact Miss Cecilia Chan at 3917 9493 or Miss Cynthia Cheung at 3917 9748.