Date: 18 January 2024 (Thursday)
Time: 5:00 pm – 6:00 pm
Venue: Cheung Kung Hai Lecture Theatre 1, G/F, William M.W. Mong Block, 21 Sassoon Road

5:00 p.m.

Presenter: Darsh Arvindbhai VAGHANI (MPhil candidate)
Primary Supervisor: Prof. Martin CHEUNG
Presentation Title: Identification of protective factors in oculomotor neurons conferring resistance to spinal muscular atrophy
Abstract: Spinal Muscular Atrophy (SMA) is a neuromuscular degenerative disease caused by homozygous mutations or deletion of the survival motor neuron gene 1 (SMN1) gene, resulting in the loss of the ubiquitously expressed SMN1 protein. This leads to progressive and selective degeneration of spinal motor neurons and their innervation to the muscle fibers, causing muscular atrophy, immobility, and death. Although there are three FDA-approved treatments, Nusinersen, Zolgensma, and Risdiplam for restoration of SMN loss, they are not curative. Therefore, it is crucial to identify new therapeutic targets for the effective treatment of SMA. Interestingly, oculomotor neurons, responsible for eye movements, remain unaffected in SMA patients1-3, implying a unique intrinsic mechanism to protect them from degeneration in response to the loss of SMN1. Previous studies revealed preferential expression of factors in ocular motor neurons of SMA mice but not in spinal motor neurons, suggesting their protective role 4. To investigate if similar factors are expressed in human ocular motor neurons, we utilized the expression of PHOX2A as a critical determinant of these neurons to generate a knock in of the tdTomato reporter into its endogenous locus, enabling the enrichment of ocular motor neurons from induced pluripotent stem cells derived from healthy individuals and SMA patients’ urine samples for transcriptomic profiling analysis. This approach holds promise in identifying protective factors in oculomotor neurons that confer resistance to SMA and may serve as new therapeutic targets to enhance the efficacy of SMA treatments.

5:30 p.m.

Presenter: Zhe WANG (MPhil candidate)
Primary Supervisor: Dr. Xiucong BAO
Presentation Title: Estrogen activation on H3K79me2-mediated menin-chromatin interaction
Abstract: Breast cancer is a prevalent global diagnosis, classified into molecular subclasses to address therapy heterogeneity. In ER-positive (ER+) subtypes, inhibiting ER signaling is a key treatment strategy, improving patient survival rates. Epigenetic modulations, specifically involving coactivator and corepressor complexes, play a crucial role in breast cancer. DOT1L, an enzyme responsible for the methylation of histone H3 on lysine-79 (H3K79me), has been recognized as a vital constituent of these multiprotein complexes. Menin, a part of the MLL1/MLL2 (lysine methyltransferase) complexes, is capable of interactive activation with ERalpha to act as a key driver in sporadic breast cancer cases. Recent advances in nucleosome-based photoaffinity probes and quantitative proteomics have identified menin as a specific "reader" of di-methylated H3K79 (H3K79me2). DOT1L inhibitor eradicated global H3K79me2 levels, disrupting menin-chromatin interaction. Interestingly, exogenous estrogen dosage didn’t disrupt the menin-chromatin interaction, despite DOT1L inhibition. To understand the dynamics between epigenetic modulations and hormone receptor interactions, proteomic and genomic approaches will be used to explore the influence of estrogen activation on H3K79me2-mediated menin/chromatin interaction in breast cancer cells.

ALL ARE WELCOME

Should you have any enquiries, please feel free to contact Jerry Siu at 3917 6912.