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Article ; Online: Replication and innate immune responses of two chikungunya virus genotypes in human monocyte-derived macrophages.

Lau, Joanne Zhi Han / Chua, Chong Long / Chan, Yoke Fun / Nadarajan, Veera Sekaran / Lee, Christina Lai Ling / Sam, I-Ching

The Journal of general virology

2023 Volume 104, Issue 4

Abstract: Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which causes epidemics of fever, joint pain and rash. There are three genotypes: West African, East/Central/South/Africa (ECSA) and Asian, with the latter two predominant globally. Genotype- ...

Abstract	Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which causes epidemics of fever, joint pain and rash. There are three genotypes: West African, East/Central/South/Africa (ECSA) and Asian, with the latter two predominant globally. Genotype-specific differences in clinical presentations, virulence and immunopathology have been described. Macrophages are key cells in immune responses against CHIKV. Circulating blood monocytes enter tissue to differentiate into monocyte-derived macrophages (MDMs) in response to CHIKV infection at key replication sites such as lymphoid organs and joints. This study analyses differences in replication and induced immune mediators following infection of MDMs with Asian and ECSA CHIKV genotypes. Primary human MDMs were derived from residual blood donations. Replication of Asian (MY/06/37348) or ECSA (MY/08/065) genotype strains of CHIKV in MDMs was measured by plaque assay. Nineteen immune mediators were measured in infected cell supernatants using multiplexed immunoassay or ELISA. MY/08/065 showed significantly higher viral replication at 24 h post-infection (h p.i.) but induced significantly lower expression of proinflammatory cytokines (CCL-2, CCL-3, CCL-4, RANTES and CXCL-10) and the anti-inflammatory IL-1Ra compared to MY/06/37348. No differences were seen at later time points up to 72 h p.i. During early infection, MY/08/065 induced lower proinflammatory immune responses in MDMs.
MeSH term(s)	Animals ; Humans ; Chikungunya virus/genetics ; Chikungunya Fever ; Immunity, Innate ; Macrophages ; Virus Replication ; Genotype
Language	English
Publishing date	2023-04-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001842
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Article ; Online: Vestibular Rehabilitation Therapy for the Treatment of Vestibular Migraine, and the Impact of Traumatic Brain Injury on Outcome: A Retrospective Study.

Stancel-Lewis, Jack / Lau, Joanne Wai Ling / Male, Amanda / Korres, George / Rogel-Salazar, Jesus / Pavlou, Marousa / Bamiou, Doris-Eva

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology

2022 Volume 43, Issue 3, Page(s) 359–367

Abstract: Introduction: Vestibular migraine (VM) is a common condition; individuals experience dizziness with migraine symptoms. Vestibular rehabilitation therapy (VRT) has been reported as an effective treatment for VM, however, evidence is limited. VM and ... ...

Abstract	Introduction: Vestibular migraine (VM) is a common condition; individuals experience dizziness with migraine symptoms. Vestibular rehabilitation therapy (VRT) has been reported as an effective treatment for VM, however, evidence is limited. VM and traumatic brain injury (TBI) can co-occur, and some suggest that TBI can induce VM. There is limited evidence on the effect a history of TBI has on VRT in patients with VM. Methods: Retrospective case series of 93 (f = 63, m = 30) participants with VM and underwent VRT (mean age 48.62; SD 15.92). Pre- and post-treatment self-reported outcome measures and functional gait assessment were extracted from the participants health records and evaluated. The impact of TBI on VRT outcome in participants with VM was analyzed. Individuals with TBI and no history of migraine (n = 40) were also extracted to act as a control. Results: VRT significantly improved self-reported dizziness on the Dizziness Handicap Inventory (DHI), with a mean change of -18 points (p < 0.000) and +5 points on the functional gait assessment (FGA) (p < 0.000) in patients with VM. A history of TBI significantly impacted outcome on the DHI (p = 0.018) in patients with VM.VRT significantly improved all outcome measures for individuals with TBI, with a mean change of -16 points on the DHI (p = 0.001) and +5 points on the FGA (p < 0.000). VM presence significantly impacted outcome. Conclusion: VRT should be considered as a treatment option to reduce dizziness and the risk of falls in individuals with VM. TBI may negatively impact VRT outcomes in individuals with VM.
MeSH term(s)	Brain Injuries, Traumatic/complications ; Dizziness/diagnosis ; Humans ; Middle Aged ; Migraine Disorders/complications ; Migraine Disorders/diagnosis ; Retrospective Studies ; Vertigo/complications ; Vestibular Diseases/complications ; Vestibular Diseases/diagnosis
Language	English
Publishing date	2022-02-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2036790-9
ISSN	1537-4505 ; 1531-7129
ISSN (online)	1537-4505
ISSN	1531-7129
DOI	10.1097/MAO.0000000000003452
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Article: Rituximab for Autoimmune Encephalitis with Epilepsy.

Kurukumbi, Mohankumar / Dave, Rahul H / Castillo, Jose / Shah, Tulsi / Lau, Joanne

Case reports in neurological medicine

2020 Volume 2020, Page(s) 5843089

Abstract: Intractable epilepsy remains a significant medical challenge, resulting in recurrent and prolonged intensive care unit (ICU) admissions. Autoimmune encephalitis is emerging as a treatable cause of intractable epilepsy. It is characterized by antibodies ... ...

Abstract	Intractable epilepsy remains a significant medical challenge, resulting in recurrent and prolonged intensive care unit (ICU) admissions. Autoimmune encephalitis is emerging as a treatable cause of intractable epilepsy. It is characterized by antibodies against cerebral antigens, such as potassium channels such as leucine-rich, glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2), calcium channels such as the voltage-gated calcium channel (VGCC), or neurotransmitter receptors such as the
Language	English
Publishing date	2020-06-23
Publishing country	United States
Document type	Case Reports
ZDB-ID	2629909-4
ISSN	2090-6676 ; 2090-6668
ISSN (online)	2090-6676
ISSN	2090-6668
DOI	10.1155/2020/5843089
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Article: Atrial Fibrillation and Ventricular Tachycardia in a Patient with Cardiac Sarcoidosis.

Lau, Joanne / Syed, Huzaefah J / Ellenbogen, Kenneth A / Kron, Jordana

The Journal of innovations in cardiac rhythm management

2018 Volume 9, Issue 2, Page(s) 3016–3021

Abstract: Cardiac sarcoidosis (CS) can cause atrial and ventricular arrhythmias, conduction system disease, and congestive heart failure. The use of advanced imaging modalities including cardiac magnetic resonance and positron emission tomography with 2-deoxy-2-[ ... ...

Abstract	Cardiac sarcoidosis (CS) can cause atrial and ventricular arrhythmias, conduction system disease, and congestive heart failure. The use of advanced imaging modalities including cardiac magnetic resonance and positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose can be helpful in evaluating the extent of disease and response to treatment. The management of CS patients can be challenging, requiring immunosuppression medications, antiarrhythmic drugs, implantable cardiac devices, and cardiac ablation procedures. We report a patient with CS initially presenting with paroxysmal atrial fibrillation who later developed polymorphic ventricular tachycardia, highlighting the complexity of diagnosis and management in patients with multisystem sarcoidosis.
Language	English
Publishing date	2018-02-15
Publishing country	United States
Document type	Case Reports
ISSN	2156-3977
ISSN	2156-3977
DOI	10.19102/icrm.2018.090203
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Article ; Online: Bilateral sudden sensorineural hearing loss in Staphylococcus aureus endocarditis.

Lau, Joanne Wai Ling / Ceranic, Borka / Harris, Robert / Timehin, Elwina

BMJ case reports

2015 Volume 2015

Abstract: This case highlights the diagnostic challenges in patients presenting with bilateral sudden sensorinueral hearing loss (SNHL). The aetiology of bilateral sudden SNHL may span several medical disciplines. Therefore, clinicians should be mindful of such ... ...

Abstract	This case highlights the diagnostic challenges in patients presenting with bilateral sudden sensorinueral hearing loss (SNHL). The aetiology of bilateral sudden SNHL may span several medical disciplines. Therefore, clinicians should be mindful of such presentations, and consider aetiologies beyond otological and neurological causes. We present a case of a previously healthy 51-year-old woman who presented with coryzal symptoms and sudden audiovestibular failure. Examination revealed fever, tachycardia, bilateral profound hearing loss and nystagmus. Following investigations, an initial working diagnosis of vasculitis was made. Later, blood cultures revealed methicillin-sensitive Staphylococcus aureus (MSSA) and a transoesophageal echocardiogram confirmed endocarditis. The patient made a good recovery, but the hearing loss was permanent and managed with a cochlear implant.
MeSH term(s)	Deafness/diagnosis ; Deafness/etiology ; Deafness/microbiology ; Endocarditis, Bacterial/complications ; Endocarditis, Bacterial/diagnosis ; Endocarditis, Bacterial/microbiology ; Female ; Hearing Loss, Bilateral/diagnosis ; Hearing Loss, Bilateral/etiology ; Hearing Loss, Bilateral/microbiology ; Hearing Loss, Sensorineural/diagnosis ; Hearing Loss, Sensorineural/etiology ; Hearing Loss, Sensorineural/microbiology ; Hearing Loss, Sudden/diagnosis ; Hearing Loss, Sudden/etiology ; Hearing Loss, Sudden/microbiology ; Humans ; Middle Aged ; Staphylococcal Infections/complications ; Staphylococcal Infections/microbiology ; Staphylococcus aureus
Language	English
Publishing date	2015-09-14
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2015-211700
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Article ; Online: A Phosphosignaling Adaptor Primes the AAA+ Protease ClpXP to Drive Cell Cycle-Regulated Proteolysis.

Lau, Joanne / Hernandez-Alicea, Lisa / Vass, Robert H / Chien, Peter

Molecular cell

2015 Volume 59, Issue 1, Page(s) 104–116

Abstract: The response regulator CpdR couples phosphorylation events in Caulobacter crescentus with the AAA+ protease ClpXP to provide punctuated degradation of crucial substrates involved in cell cycle regulation. CpdR functions like an adaptor to alter substrate ...

Abstract	The response regulator CpdR couples phosphorylation events in Caulobacter crescentus with the AAA+ protease ClpXP to provide punctuated degradation of crucial substrates involved in cell cycle regulation. CpdR functions like an adaptor to alter substrate choice by ClpXP; however, it remains unclear how CpdR influences its multiple targets. Here we show that, unlike canonical ClpXP adaptors, CpdR alone does not strongly bind its substrate. Instead, CpdR binds the N-terminal domain of ClpX and prepares (primes) the unfoldase for substrate engagement. This priming creates a recruitment interface that docks multiple substrates and additional adaptor components. We show that adaptor-dependent priming of ClpX avoids concentration-dependent inhibition that limits traditional scaffolding adaptors. Phosphosignaling disrupts the adaptor-protease interaction, and mutations in CpdR that impact ClpX binding tune adaptor activity and biological function. Together, these results reveal how a single adaptor can command global changes in proteome composition through priming of a protease.
MeSH term(s)	Adenosine Triphosphatases/metabolism ; Bacterial Proteins/metabolism ; Binding Sites/genetics ; Caulobacter crescentus/genetics ; Caulobacter crescentus/metabolism ; Cell Cycle/genetics ; Cell Cycle Checkpoints/genetics ; Endopeptidase Clp/metabolism ; Phosphorylation ; Protein Binding ; Protein Structure, Tertiary ; Proteolysis
Chemical Substances	Bacterial Proteins ; Endopeptidase Clp (EC 3.4.21.92) ; Adenosine Triphosphatases (EC 3.6.1.-)
Language	English
Publishing date	2015-07-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2015.05.014
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Article ; Online: Phenotyping clonal populations of glioma stem cell reveals a high degree of plasticity in response to changes of microenvironment.

Innes, James A / Lowe, Andrew S / Fonseca, Raquel / Aley, Natasha / El-Hassan, Tedani / Constantinou, Myrianni / Lau, Joanne / Eddaoudi, Ayad / Marino, Silvia / Brandner, Sebastian

Laboratory investigation; a journal of technical methods and pathology

2021 Volume 102, Issue 2, Page(s) 172–184

Abstract: The phenotype of glioma-initiating cells (GIC) is modulated by cell-intrinsic and cell-extrinsic factors. Phenotypic heterogeneity and plasticity of GIC is an important limitation to therapeutic approaches targeting cancer stem cells. Plasticity also ... ...

Abstract	The phenotype of glioma-initiating cells (GIC) is modulated by cell-intrinsic and cell-extrinsic factors. Phenotypic heterogeneity and plasticity of GIC is an important limitation to therapeutic approaches targeting cancer stem cells. Plasticity also presents a challenge to the identification, isolation, and propagation of purified cancer stem cells. Here we use a barcode labelling approach of GIC to generate clonal populations over a number of passages, in combination with phenotyping using the established stem cell markers CD133, CD15, CD44, and A2B5. Using two cell lines derived from isocitrate dehydrogenase (IDH)-wildtype glioblastoma, we identify a remarkable heterogeneity of the phenotypes between the cell lines. During passaging, clonal expansion manifests as the emergence of a limited number of barcoded clones and a decrease in the overall number of clones. Dual-labelled GIC are capable of forming traceable clonal populations which emerge after as few as two passages from mixed cultures and through analyses of similarity of relative proportions of 16 surface markers we were able to pinpoint the fate of such populations. By generating tumour organoids we observed a remarkable persistence of dominant clones but also a significant plasticity of stemness marker expression. Our study presents an experimental approach to simultaneously barcode and phenotype glioma-initiating cells to assess their functional properties, for example to screen newly established GIC for tumour-specific therapeutic vulnerabilities.
MeSH term(s)	AC133 Antigen/immunology ; AC133 Antigen/metabolism ; Antigens, CD/immunology ; Antigens, CD/metabolism ; Biomarkers, Tumor/immunology ; Biomarkers, Tumor/metabolism ; Brain Neoplasms/immunology ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Cells, Cultured ; Clone Cells/immunology ; Clone Cells/metabolism ; Flow Cytometry ; Glioma/immunology ; Glioma/metabolism ; Glioma/pathology ; Humans ; Hyaluronan Receptors/immunology ; Hyaluronan Receptors/metabolism ; Immunophenotyping ; Lewis X Antigen/immunology ; Lewis X Antigen/metabolism ; Microscopy, Confocal ; Neoplastic Stem Cells/classification ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/metabolism ; Tumor Microenvironment/immunology
Chemical Substances	AC133 Antigen ; Antigens, CD ; Biomarkers, Tumor ; Hyaluronan Receptors ; Lewis X Antigen
Language	English
Publishing date	2021-11-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80178-1
ISSN	1530-0307 ; 0023-6837
ISSN (online)	1530-0307
ISSN	0023-6837
DOI	10.1038/s41374-021-00695-2
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Article ; Online: Brain-derived neurotrophic factor derived from sensory neurons plays a critical role in chronic pain.

Sikandar, Shafaq / Minett, Michael S / Millet, Queensta / Santana-Varela, Sonia / Lau, Joanne / Wood, John N / Zhao, Jing

Brain : a journal of neurology

2018 Volume 141, Issue 4, Page(s) 1028–1039

Abstract: Many studies support the pro-nociceptive role of brain-derived neurotrophin factor (BDNF) in pain processes in the peripheral and central nervous system. We have previously shown that nociceptor-derived BDNF is involved in inflammatory pain. Microglial- ... ...

Abstract	Many studies support the pro-nociceptive role of brain-derived neurotrophin factor (BDNF) in pain processes in the peripheral and central nervous system. We have previously shown that nociceptor-derived BDNF is involved in inflammatory pain. Microglial-derived BDNF has also been shown to be involved in neuropathic pain. However, the distinct contribution of primary afferent-derived BNDF to chronic pain processing remains undetermined. In this study, we used Avil-CreERT2 mice to delete Bdnf from all adult peripheral sensory neurons. Conditional BDNF knockouts were healthy with no sensory neuron loss. Behavioural assays and in vivo electrophysiology indicated that spinal excitability was normal. Following formalin inflammation or neuropathy with a modified Chung model, we observed normal development of acute pain behaviour, but a deficit in second phase formalin-induced nocifensive responses and a reversal of neuropathy-induced mechanical hypersensitivity during the later chronic pain phase in conditional BDNF knockout mice. In contrast, we observed normal development of acute and chronic neuropathic pain in the Seltzer model, indicating differences in the contribution of BDNF to distinct models of neuropathy. We further used a model of hyperalgesic priming to examine the contribution of primary afferent-derived BDNF in the transition from acute to chronic pain, and found that primed BDNF knockout mice do not develop prolonged mechanical hypersensitivity to an inflammatory insult. Our data suggest that BDNF derived from sensory neurons plays a critical role in mediating the transition from acute to chronic pain.
MeSH term(s)	Animals ; Brain-Derived Neurotrophic Factor/genetics ; Brain-Derived Neurotrophic Factor/metabolism ; Carrageenan/toxicity ; Chronic Pain/chemically induced ; Chronic Pain/pathology ; Disease Models, Animal ; Female ; Formaldehyde/toxicity ; Ganglia, Spinal/pathology ; Hyperalgesia/etiology ; Male ; Mice ; Mice, Transgenic ; Microfilament Proteins/genetics ; Microfilament Proteins/metabolism ; Pain Measurement ; Sensory Receptor Cells/metabolism
Chemical Substances	Avil protein, mouse ; Brain-Derived Neurotrophic Factor ; Microfilament Proteins ; Formaldehyde (1HG84L3525) ; Carrageenan (9000-07-1)
Language	English
Publishing date	2018-03-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awy009
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Article: A Phosphosignaling Adaptor Primes the AAA+ Protease ClpXP to Drive Cell Cycle-Regulated Proteolysis

Lau, Joanne / Lisa Hernandez-Alicea / Peter Chien / RobertÂ H. Vass

Molecular cell. 2015 July 02, v. 59

2015

Abstract	The response regulator CpdR couples phosphorylation events in Caulobacter crescentus with the AAA+ protease ClpXP to provide punctuated degradation of crucial substrates involved in cell cycle regulation. CpdR functions like an adaptor to alter substrate choice by ClpXP; however, it remains unclear how CpdR influences its multiple targets. Here we show that, unlike canonical ClpXP adaptors, CpdR alone does not strongly bind its substrate. Instead, CpdR binds the N-terminal domain of ClpX and prepares (primes) the unfoldase for substrate engagement. This priming creates a recruitment interface that docks multiple substrates and additional adaptor components. We show that adaptor-dependent priming of ClpX avoids concentration-dependent inhibition that limits traditional scaffolding adaptors. Phosphosignaling disrupts the adaptor-protease interaction, and mutations in CpdR that impact ClpX binding tune adaptor activity and biological function. Together, these results reveal how a single adaptor can command global changes in proteome composition through priming of a protease.
Keywords	bioactive properties ; Caulobacter crescentus ; cell cycle ; mutation ; phosphorylation ; proteinases ; proteolysis ; proteome
Language	English
Dates of publication	2015-0702
Size	p. 104-116.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2015.05.014
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Article ; Online: The association between cardiac physiology, acquired brain injury, and postnatal brain growth in critical congenital heart disease.

Peyvandi, Shabnam / Kim, Hosung / Lau, Joanne / Barkovich, A James / Campbell, Andrew / Miller, Steven / Xu, Duan / McQuillen, Patrick

The Journal of thoracic and cardiovascular surgery

2017 Volume 155, Issue 1, Page(s) 291–300.e3

Abstract: Objective: To assess the trajectory of perioperative brain growth in relationship to cardiac diagnosis and acquired brain injuries.: Methods: This was a cohort study of term neonates with hypoplastic left heart syndrome (HLHS) and d-transposition of ... ...

Abstract	Objective: To assess the trajectory of perioperative brain growth in relationship to cardiac diagnosis and acquired brain injuries. Methods: This was a cohort study of term neonates with hypoplastic left heart syndrome (HLHS) and d-transposition of the great arteries (d-TGA). Subjects underwent magnetic resonance imaging of the brain pre- and postoperatively to determine the severity of brain injury and total and regional brain volumes by the use of automated morphometry. Comparisons were made by cardiac lesion and injury status. Results: A total of 79 subjects were included (49, d-TGA; 30, HLHS). Subjects with HLHS had more postoperative brain injury (55.6% vs 30.4%, P = .03) and more severe brain injury (moderate-to-severe white matter [WM] injury, P = .01). Total and regional perioperative brain growth was not different by brain injury status (either pre- or postoperative). However, subjects with moderate-to-severe WM injury had a slower rate of brain growth in WM and gray matter compared with those with no injury. Subjects with HLHS had a slower rate of growth globally and in WM and deep gray matter as compared with d-TGA (total brain volume: 12 cm Conclusions: Neonates with HLHS have a slower rate of global and regional brain growth compared with d-TGA, likely related to inherent physiologic differences postoperatively. These findings demonstrate the complex interplay between cardiac lesion, brain injury, and brain growth.
MeSH term(s)	Brain/diagnostic imaging ; Brain/growth & development ; Brain Injuries/diagnosis ; Brain Injuries/etiology ; California ; Cardiovascular System/physiopathology ; Cohort Studies ; Correlation of Data ; Female ; Gestational Age ; Humans ; Hypoplastic Left Heart Syndrome/physiopathology ; Hypoplastic Left Heart Syndrome/surgery ; Infant, Newborn ; Magnetic Resonance Imaging/methods ; Male ; Perioperative Care/methods ; Postoperative Complications/diagnosis ; Transposition of Great Vessels/physiopathology ; Transposition of Great Vessels/surgery
Language	English
Publishing date	2017-08-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	3104-5
ISSN	1097-685X ; 0022-5223
ISSN (online)	1097-685X
ISSN	0022-5223
DOI	10.1016/j.jtcvs.2017.08.019
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