A5061023158- Cell death mechanisms and regulation
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Sirtuins and Resveratrol in Medicine
- Muscle Physiology and Disorders
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Hair Growth and Disorders
- Ubiquitin and proteasome pathways
- Cancer and Skin Lesions
- Cancer-related Molecular Pathways
- Chronic Myeloid Leukemia Treatments
- Cell Adhesion Molecules Research
- Eosinophilic Disorders and Syndromes
- Acute Myeloid Leukemia Research
- ATP Synthase and ATPases Research
- Caveolin-1 and cellular processes
- Phagocytosis and Immune Regulation
Duke-NUS Medical School
2021-2025
Walter and Eliza Hall Institute of Medical Research
2015-2022
The University of Melbourne
2015-2022
Mitochondrial apoptosis is mediated by BAK and BAX, two proteins that induce mitochondrial outer membrane permeabilization, leading to cytochrome c release activation of apoptotic caspases. In the absence active caspases, DNA (mtDNA) triggers innate immune cGAS/STING pathway, causing dying cells secrete type I interferon. How cGAS gains access mtDNA remains unclear. We used live-cell lattice light-sheet microscopy examine network in mouse embryonic fibroblasts. found after BAK/BAX loss,...
Intrinsic apoptosis is critical to prevent tumor formation and engaged by many anti-cancer agents eliminate cells. BAX BAK, the two essential mediators of apoptosis, are thought be regulated through similar mechanisms act redundantly drive apoptotic cell death. From an unbiased genome-wide CRISPR/Cas9 screen, we identified VDAC2 (voltage-dependent anion channel 2) as important for BAX, but not function. Genetic deletion abrogated association BAK with mitochondrial complexes containing VDAC1,...
Tetraspanins, a superfamily of membrane proteins, mediate diverse biological processes through tetraspanin-enriched microdomains in the plasma membrane. However, how their cell-surface presentation is controlled remains unclear. To identify regulators tetraspanin trafficking, we conduct sequential genome-wide loss-of-function CRISPR-Cas9 screens based on expression member, TSPAN8. Several genes potentially involved endoplasmic reticulum (ER) targeting, different Golgi apparatus, and protein...
Abstract Hair follicles cycle through expansion, regression and quiescence. To investigate the role of MCL‑1, a BCL‑2 family protein with anti‑apoptotic apoptosis‑unrelated functions, we delete Mcl‑1 within skin epithelium using constitutive inducible systems. Constitutive deletion does not impair hair follicle organogenesis but leads to gradual loss elimination stem cells. Acute rapidly depletes activated cells completely blocks depilation‑induced regeneration in adult mice, while quiescent...
The commonality between various muscle diseases is the loss of mass, function, and regeneration, which severely restricts mobility impairs quality life. With stem cells (MuSCs) playing a key role in facilitating repair, targeting regulators regeneration has been shown to be promising therapeutic approach repair muscles. However, underlying molecular mechanisms driving are complex poorly understood. Here, we identified new regulator Deaf1 (Deformed epidermal autoregulatory factor-1) -...
Both germline polymorphisms and tumor-specific genetic alterations can determine the response of a cancer to given therapy. We previously reported deletion polymorphism in BIM gene that was sufficient mediate intrinsic resistance tyrosine kinase inhibitors (TKI) chronic myeloid leukemia (CML), as well other cancers [1]. The favored generation splice forms lacking pro-apoptotic BH3 domain, conferring relative TKI imatinib (IM). However, CML patients with developed both partial complete IM...
The commonality between various muscle diseases is the loss of mass, function, and regeneration, which severely restricts mobility impairs quality life. With stem cells (MuSCs) playing a key role in facilitating repair, targeting regulators regeneration has been shown to be promising therapeutic approach repair muscles. However, underlying molecular mechanisms driving are complex poorly understood. Here, we identified new regulator Deformed epidermal autoregulatory factor 1 (Deaf1) -...
Abstract Intrinsic apoptosis is critical for normal physiology including the prevention of tumor formation. BAX and BAK are essential mediating this process cytotoxic action many anticancer drugs. thought to act in a functionally redundant manner considered be regulated similarly. From an unbiased genome-wide CRISPR/Cas9 screen, we identified VDAC2 (voltage-dependent anion channel 2) as BAX, but not BAK, function. The genetic deletion abrogated association with mitochondrial complexes that...
SUMMARY Intrinsic apoptosis is principally governed by the BCL-2 family of proteins, but some non-BCL-2 proteins are also critical to control this process. To identify novel regulators, we performed a genome-wide CRISPR-Cas9 library screen, and it identified mitochondrial E3 ubiquitin ligase MARCHF5/MITOL/RNF153 as an important regulator BAK apoptotic function. Deleting MARCHF5 in diverse cell lines dependent on conferred profound resistance BH3-mimetic drugs. The loss or its activity...