Kenneth Pang - Academia.edu (original) (raw)

Papers by Kenneth Pang

The Lancet Child & Adolescent Health, 2021

Increasing numbers of children and adolescents are being referred to gender services for gender-r... more Increasing numbers of children and adolescents are being referred to gender services for gender-related concerns. Various instruments are used with these patients in clinical care, but their clinical validity, strengths, and limitations have not been systematically reviewed. In this systematic review, we searched MEDLINE, PubMed, and PsycINFO databases for available tools that assess gender identity, gender expression, or gender dysphoria in transgender and gender-diverse (TGD) children and adolescents. We included studies published before Jan 20, 2020, that used tools to assess gender identity, expression, or dysphoria in TGD individuals younger than 18 years. Data were extracted from eligible studies using a standardised form. We found 39 studies that met the inclusion criteria, from which we identified 24 tools. The nature of tools varied considerably and included direct observation, child and adolescent self-report, and parent-report tools. Many methods have only been used with small samples, include outdated content, and lack evaluation of psychometric properties. In summary, a paucity of studies in this area, along with sparse reporting of psychometric properties, made it difficult to compare the relative use of tools, and current tools have substantial limitations. Future research is required to validate existing measures and create more relevant, culturally appropriate tools.

Cell Reports, Jul 1, 2017

X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyper... more X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP. Importantly, deletion of TNFR2 in XIAP-deficient cells limited TLR-MyD88-induced cIAP1-TRAF2 degradation, cell death, and IL-1β activation. In contrast to TLR-MyD88, TLR-TRIF-induced interferon (IFN)β inhibited cIAP1 loss and consequent cell death. These data reveal how, upon XIAP deficiency, a TLR-TNF-TNFR2 axis drives cIAP1-TRAF2 degradation to allow TLR or TNFR1 activation of RIPK3-caspase-8 and IL-1β. This mechanism may explain why XIAP-deficient patients can exhibit symptoms reminiscent of patients with activating inflammasome mutations.

Immunology and Cell Biology

The role of the immunoproteasome is perceived as confined to adaptive immune responses given its ... more The role of the immunoproteasome is perceived as confined to adaptive immune responses given its ability to produce peptides ideal for MHC Class-I binding. Here, we demonstrate that the immunoproteasome subunit, LMP2, has functions beyond its immunomodulatory role. Using LMP2-deficient mice, we demonstrate that LMP2 is crucial for lymphocyte development and survival in the periphery. Moreover, LMP2-deficient lymphocytes show impaired degradation of key BH3-only proteins, resulting in elevated levels of proapoptotic BIM and increased cell death. Interestingly, LMP2 is the sole immunoproteasome subunit required for BIM degradation. Together, our results suggest LMP2 has important housekeeping functions and represents a viable therapeutic target for cancer.

Yearbook of Paediatric Endocrinology

Hormonal interventions are being increasingly used to treat young people with gender dysphoria, b... more Hormonal interventions are being increasingly used to treat young people with gender dysphoria, but their effects in this population have not been systematically reviewed before. OBJECTIVE: To review evidence for the physical, psychosocial, and cognitive effects of gonadotropin-releasing hormone analogs (GnRHa), gender-affirming hormones, antiandrogens, and progestins on transgender adolescents.

The Lancet Child & Adolescent Health, 2021

Increasing numbers of children and adolescents are being referred to gender services for gender-r... more Increasing numbers of children and adolescents are being referred to gender services for gender-related concerns. Various instruments are used with these patients in clinical care, but their clinical validity, strengths, and limitations have not been systematically reviewed. In this systematic review, we searched MEDLINE, PubMed, and PsycINFO databases for available tools that assess gender identity, gender expression, or gender dysphoria in transgender and gender-diverse (TGD) children and adolescents. We included studies published before Jan 20, 2020, that used tools to assess gender identity, expression, or dysphoria in TGD individuals younger than 18 years. Data were extracted from eligible studies using a standardised form. We found 39 studies that met the inclusion criteria, from which we identified 24 tools. The nature of tools varied considerably and included direct observation, child and adolescent self-report, and parent-report tools. Many methods have only been used with small samples, include outdated content, and lack evaluation of psychometric properties. In summary, a paucity of studies in this area, along with sparse reporting of psychometric properties, made it difficult to compare the relative use of tools, and current tools have substantial limitations. Future research is required to validate existing measures and create more relevant, culturally appropriate tools.

Cell Reports, Jul 1, 2017

X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyper... more X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP. Importantly, deletion of TNFR2 in XIAP-deficient cells limited TLR-MyD88-induced cIAP1-TRAF2 degradation, cell death, and IL-1β activation. In contrast to TLR-MyD88, TLR-TRIF-induced interferon (IFN)β inhibited cIAP1 loss and consequent cell death. These data reveal how, upon XIAP deficiency, a TLR-TNF-TNFR2 axis drives cIAP1-TRAF2 degradation to allow TLR or TNFR1 activation of RIPK3-caspase-8 and IL-1β. This mechanism may explain why XIAP-deficient patients can exhibit symptoms reminiscent of patients with activating inflammasome mutations.

Immunology and Cell Biology

The role of the immunoproteasome is perceived as confined to adaptive immune responses given its ... more The role of the immunoproteasome is perceived as confined to adaptive immune responses given its ability to produce peptides ideal for MHC Class-I binding. Here, we demonstrate that the immunoproteasome subunit, LMP2, has functions beyond its immunomodulatory role. Using LMP2-deficient mice, we demonstrate that LMP2 is crucial for lymphocyte development and survival in the periphery. Moreover, LMP2-deficient lymphocytes show impaired degradation of key BH3-only proteins, resulting in elevated levels of proapoptotic BIM and increased cell death. Interestingly, LMP2 is the sole immunoproteasome subunit required for BIM degradation. Together, our results suggest LMP2 has important housekeeping functions and represents a viable therapeutic target for cancer.

Yearbook of Paediatric Endocrinology

Hormonal interventions are being increasingly used to treat young people with gender dysphoria, b... more Hormonal interventions are being increasingly used to treat young people with gender dysphoria, but their effects in this population have not been systematically reviewed before. OBJECTIVE: To review evidence for the physical, psychosocial, and cognitive effects of gonadotropin-releasing hormone analogs (GnRHa), gender-affirming hormones, antiandrogens, and progestins on transgender adolescents.