José Alejandro Lopez

Regional scientific meetings occupy a distinctive but underexamined position within the research ecosystem. Smaller and more accessible than national congresses, yet broader in scope than institutional seminar programm, they provide opportunities for repeated interactions across institutions, career stages, and research domains. The Brisbane Immunology Group (BIG) meeting is one of the longest‐running and most influential regional meetings associated with the Australian and New Zealand Society for Immunology (ASI), providing a focal point for immunology researchers across Queensland, Australia, and beyond. This article examines the BIG meeting as a case study of a regional immunology community that has sustained scientific engagement, mentoring, and collaboration for 25 years. Drawing on historical records and thematic analysis of interviews with organizers, senior contributors, and recent attendees, we identify six characteristics that have contributed to the longevity and impact of the meeting: accessibility, cross‐institutional ownership, intergenerational participation, social integration, programmatic continuity with adaptive innovation, and deliberate recognition of community contributions. We argue that BIG functions not merely as an annual scientific meeting but as a regional community of practice that supports scientific collaboration, professional identity formation, and leadership development. The BIG experience provides broader lessons regarding the role of regional meetings in strengthening scientific communities, supporting future scientific leaders and sustaining disciplinary vitality.

CEP55, a centrosomal protein frequently overexpressed in multiple cancers, is implicated in regulation of genomic instability and PI3K/AKT pathway activation, yet its role in tumor progression and the tumor microenvironment remains incompletely defined. Here, we developed an inducible Cep55 knockout (KO) mouse model and complementary primary, immortalized, and transformed mouse embryonic fibroblast (MEF) systems and employ integrative multi‐omics analyses to define CEP55‐driven mechanisms and validated findings in human cancer datasets. Cep55 deletion is well tolerated in adult tissues but significantly delays tumor onset and progression in E1A/Ras‐driven models and prolongs survival in PTEN‐deficient cancer models. Mechanistically, spatial transcriptomic and proteomic analyses revealed that CEP55 regulates extracellular matrix (ECM) remodeling, integrin signaling, and cell adhesion pathways, AKT/ERK signaling and cellular stress responses. Importantly, loss of Cep55 also reprograms the tumor immune microenvironment, reducing tumor‐supportive macrophage polarization and enhancing antigen‐specific CD8 ⁺ T‐cell responses in vitro. Collectively, these findings demonstrate that CEP55 is dispensable for adult tissue homeostasis but plays a critical role in tumor progression by coordinating oncogenic signaling, extracellular matrix dynamics, and tumor–immune interactions and highlight it as a potential therapeutic target in aggressive and immune‐resistant cancers.

Age is a critical factor in immune responses to infection. In malaria, severe disease risk increases with age in non-immune individuals. Malaria severity is in part driven by inflammation, but mechanisms contributing to age-dependent disease risk are incompletely understood. We assessed inflammatory cytokines during malaria in non-immune children and adults, and innate cell responses in vitro to malaria parasites in naive children and adults. We show during malaria age is associated with increased inflammatory chemokines CCL2, CCL3, CXCL8, CXCL9, along with CRP, and IDO, which associate with symptoms. In naive individuals, classical monocyte and Vδ2⁺ γδ T cells from adults have higher inflammatory cytokine production, and transcriptional activation following stimulation with parasites. Classical monocyte responses in adults are dominated by CCL2, while in children increased IL10 and enrichment of IL10 signaling pathways is detected. Findings identify age-dependent cellular mechanisms that play crucial roles in driving inflammatory responses in malaria.

Plasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse the immune landscape with single cell RNA sequencing during P. falciparum malaria. We identify cell type specific responses in sub-clustered major immune cell types. Malaria is associated with an increase in immunosuppressive monocytes, alongside NK and γδ T cells which up-regulate tolerogenic markers. IL-10-producing Tr1 CD4 T cells and IL-10-producing regulatory B cells are also induced. Type I interferon responses are identified across all cell types, suggesting Type I interferon signalling may be linked to induction of immunoregulatory networks during malaria. These findings provide insights into cell-specific and shared immunoregulatory changes during malaria and provide a data resource for further analysis.

The development of highly effective malaria vaccines and improvement of drug-treatment protocols to boost antiparasitic immunity are critical for malaria elimination. However, the rapid establishment of parasite-specific immune regulatory networks following exposure to malaria parasites hampers these efforts. Here, we identified stimulator of interferon genes (STING) as a critical mediator of type I interferon production by CD4⁺ T cells during blood-stage Plasmodium falciparum infection. The activation of STING in CD4⁺ T cells by cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) stimulated IFNB gene transcription, which promoted development of IL-10– and IFN-γ–coproducing CD4⁺ T (type I regulatory [Tr1]) cells. The critical role for type I IFN signaling for Tr1 cell development was confirmed in vivo using a preclinical malaria model. CD4⁺ T cell sensitivity to STING phosphorylation was increased in healthy volunteers following P. falciparum infection, particularly in Tr1 cells. These findings identified STING expressed by CD4⁺ T cells as an important mediator of type I IFN production and Tr1 cell development and activation during malaria.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) remains a common and difficult cancer to treat. Surgical resection and chemotherapy are standard of care and clinical outcomes remain poor. Oncolytic adenoviruses are a unique approach to the treatment of this challenging cancer, aiming to overcome the features of this disease that pose the key obstacles to standard therapies. This paper provides a detailed review of the clinical trials of conditionally-replicative adenoviruses in pancreatic cancer to date, with a brief summary of the past preclinical literature and future prospects of this therapy. Methods: MEDLINE, Embase, and clinicaltrials.gov were searched from inception to December 23rd 2022 for clinical trials of conditionally-replicative adenoviruses used in patients with pancreatic ductal adenocarcinoma. Primary features for review included patient demographics, treatment protocol including dose and administration route, adverse events, patient responses and survival rates. Results: The six published clinical trials suggest that objective clinical responses can be achieved with a tolerable level of side effects, even at high viral doses. The more clinically adaptable intravenous route of administration also appears to be as well tolerated as the more challenging intratumoural injections. Conclusion: Published clinical trials provide data of the safety and some signs of oncolytic activity of conditionally-replicative adenoviruses in patients with pancreatic cancer. Importantly, on the latest trials, the easier intravenous route of administration seems to be well tolerated and safe, providing the opportunity for further clinical evaluation. It is hoped that the ongoing clinical trials will yield more promising results of this therapeutic approach against a currently intractable disease.

Homozygous nonsense mutations in CEP55 are associated with several congenital malformations that lead to perinatal lethality suggesting that it plays a critical role in regulation of embryonic development. CEP55 has previously been studied as a crucial regulator of cytokinesis, predominantly in transformed cells, and its dysregulation is linked to carcinogenesis. However, its molecular functions during embryonic development in mammals require further investigation. We have generated a Cep55 knockout (Cep55^-/-) mouse model which demonstrated preweaning lethality associated with a wide range of neural defects. Focusing our analysis on the neocortex, we show that Cep55^-/- embryos exhibited depleted neural stem/progenitor cells in the ventricular zone as a result of significantly increased cellular apoptosis. Mechanistically, we demonstrated that Cep55-loss downregulates the pGsk3β/β-Catenin/Myc axis in an Akt-dependent manner. The elevated apoptosis of neural stem/progenitors was recapitulated using Cep55-deficient human cerebral organoids and we could rescue the phenotype by inhibiting active Gsk3β. Additionally, we show that Cep55-loss leads to a significant reduction of ciliated cells, highlighting a novel role in regulating ciliogenesis. Collectively, our findings demonstrate a critical role of Cep55 during brain development and provide mechanistic insights that may have important implications for genetic syndromes associated with Cep55-loss.

Homozygous nonsense mutations in CEP55 are associated with several congenital malformations that lead to perinatal lethality suggesting that it plays a critical role in regulation of embryonic development. CEP55 has previously been studied as a critical regulator of cytokinesis predominantly in transformed cells and its deregulation is linked to carcinogenesis. However, its molecular functions during embryonic development in mammals have not been clearly defined. We have generated a Cep55 knockout (Cep55 ^-/- ) mouse model which demonstrated perinatal lethality associated with a wide range of neural defects. Focusing our analysis on the neocortex, we show that Cep55-/- embryos exhibited depleted neural stem/progenitor cells in the ventricular zone as a result of significantly increased cellular apoptosis. Mechanistically, we demonstrated that Cep55-loss downregulates the pGsk3β/β-Catenin/Myc axis in an Akt-dependent manner. The phenotype was recapitulated using human cerebral organoids and we could rescue the phenotype by inhibiting active Gsk3β. Additionally, we show that Cep55-loss leads to a significant reduction of ciliated cells, highlighting its novel role in regulating ciliogenesis. Collectively, our findings demonstrate a critical role of Cep55 during brain development and provide mechanistic insights that may have important implications for genetic syndromes associated with Cep55-loss.

Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (Pseudechis porphyriacus) on human primary leukocytes using bead-based flow cytometry, mixed lymphocyte reaction, and cell viability assays. We show that venom treatment had a significant immunosuppressive effect, inhibiting the secretion of interleukin (IL)-2 and tumor necrosis factor (TNF) from purified human T cells by 90% or greater following stimulation with mitogen (phorbol 12-myristate 13-acetate and ionomycin) or via cluster of differentiation (CD) receptors, CD3/CD28. In contrast, venom treatment did not inhibit TNF or IL-6 release from antigen-presenting cells stimulated with lipopolysaccharide. The reduced cytokine release from T cells was not associated with inhibition of T cell proliferation or reduction of cell viability, consistent with an anti-inflammatory mechanism unrelated to the cell cycle. Deconvolution of the venom using reverse-phase HPLC identified four fractions responsible for the observed immunosuppressive activity. These data suggest that compounds from P. porphyriacus venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease.

Background: Targeted therapy is a novel, promising approach to anticancer treatment that endeavors to overcome drug resistance to traditional chemotherapies. Patients with the L858R mutation in epidermal growth factor receptor (EGFR) respond to the first generation tyrosine kinase inhibitors (TKIs); however, after one year of treatment, they may become resistant. The T790M mutation is the most probable cause for drug resistance. Third generation drugs, including Osimertinib (AZD9291), are more effective against T790M and other sensitive mutations. Osimertinib is effective against the L844V mutation, has conditional effectiveness for the L718Q mutation, and is ineffective for the Cys797Ser (C797S) mutation. Cells that have both the T790M and C797 mutations are more resistant to third generation drugs. Although research has shown that Osimertinib is an effective treatment for EGFR L844V cells, this has not been shown for cells that have the C797S mutation. This molecular mechanism has not been well‐studied.Methods: In the present study, we used the GROMACS software for molecular dynamics simulation to identify interactions between Osimertinib and the kinase part of EGFR in L844V and C797S mutants.Results: We evaluated native EGFR protein and the L844V and C797S mutations’ docking and binding energy, kI, intermolecular, internal, and torsional energy parameters. Osimertinib was effective for the EGFR L844V mutation, but not for EGFR C797S. All simulations were validated by root‐mean‐square deviation (RMSD), root‐mean square fluctuation (RMSF), and radius of gyration (ROG).Conclusion: According to our computational simulation, the results supported the experimental models and, therefore, could confirm and predict the molecular mechanism of drug efficacy.