Publications

The majority of variation in outcome following severe traumatic brain injury (TBI) remains unexplained by currently recognised prognostic factors, suggesting a contribution from unaccounted variables. One key candidate variable is neuroinflammation, including the generation of autoantibodies against brain specific antigens which have been described in some individuals following TBI. Here we hypothesised that autoantibody responses following TBI would differ between individuals, and would explain a proportion of outcome variance.

• Link: https://www.medrxiv.org/content/10.1101/2020.07.24.20161786v1

Alpha-fetoprotein (AFP) is a widely used biomarker for hepatocellular carcinoma (HCC) early detection. However, low sensitivity and false negativity of AFP raise the requirement of more effective early diagnostic approaches for HCC.

• Link: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00918-x

HuProt Autoantibodies: Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1–2 weeks after infection.

• Link: https://academic.oup.com/jid/article/222/1/158/5734989

To characterize the role of B cells on human papilloma virus (HPV)-associated cancer patient outcomes and determine the effects of radiation and PD-1 blockade on B-cell populations.

• Link: https://aacrjournals.org/clincancerres/article/26/13/3345/82679/B-Cells-Improve-Overall-Survival-in-HPV-Associated

HuProt Enzyme: Proteasome inhibitors have provided a significant advance in the treatment of multiple myeloma (MM). Consequently, there is increasing interest in developing strategies to target E3 ligases, de-ubiquitinases, and/or ubiquitin receptors within the ubiquitin proteasome pathway, with an aim to achieve more specificity and reduced side-effects. Previous studies have shown a role for the E3 ligase HUWE1 in modulating c-MYC, an oncogene frequently dysregulated in MM. Here we investigated HUWE1 in MM.

• Link: https://www.nature.com/articles/s41388-020-1345-x

Immune checkpoint inhibitors (ICIs), e.g., ipilimumab (IPI) and/or nivolumab (NIVO), produce durable survival benefit in a substantial proportion of melanoma patients but can also induce severe immune-related adverse events (irAEs) requiring treatment discontinuation. There is no biomarker to predict irAEs in ICI-treated melanoma patients. Given the similar clinical manifestation between irAEs and autoimmune disorders, we hypothesized that a subset of patients possess a subclinical baseline predisposition to developing irAEs that is characterized by specific autoantibodies (autoAbs).

• Link: https://ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3069

HuProt DNA RNA: To investigate whether the rs12569232 SNP association with Vogt-Koyanagi-Harada disease and Behcet’s disease is mediated by regulation of Linc00467 expression. The rs12569232 was associated with the expression of linc00467. The expression of linc00467 was up-regulated in PBMCs and CD4+T cells from VKH disease and BD patients. Over-expression of linc00467 increased cell viability of CD4+T cells. HUR was the common binding protein identified by the two methods and confirmed by RIP.

• Link: https://www.tandfonline.com/doi/full/10.1080/09273948.2020.1745244

Sjögren’s syndrome (SS) is a rheumatic autoimmune disease characterized by focal lymphocytic infiltrates in the lacrimal and salivary glands, severe dry mouth and eyes, pain and debilitation. Diagnosis requires autoantibodies to ubiquitous Ro antigens or a lip biopsy positive for focal lymphocytic infiltrates. Here we used human proteome arrays to identify novel antibodies in plasma from Ro positive and Ro/La antibody negative SS patients compared with healthy controls.

• Link: https://journals.aai.org/jimmunol/article/204/1_Supplement/218.20/59769/Novel-shared-antibody-specificities-in-anti-Ro-La

HuProt Autoantibodies: Similar to humans, the risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study, we show the involvement of genetic variation affecting the store-operated calcium signaling gene, Stim1, in the pathogenesis of stroke in SHR. Stim1 is a key lymphocyte activation signaling molecule and contains functional variation in SHR-A3 that diverges from stroke-resistant SHR-B2. We created a SHR-A3 congenic line in which Stim1 was substituted with the corresponding genomic segment from SHR-B2.

• Link: https://www.nature.com/articles/s41435-020-0097-5

HuProt Autoantibodies: Spontaneously hypertensive rats of the stroke‐prone line (SHR‐A3) develop hypertensive renal disease as a result of naturally occurring genetic variation. Our prior work identified a single‐nucleotide polymorphism unique to SHR‐A3 that results in truncation of the carboxy terminus of STIM1. The SHR‐B2 line, which is also hypertensive but resists hypertensive renal injury, expresses the wild‐type STIM1. STIM1 plays a central role in lymphocyte calcium signaling that directs immune effector responses. Here we show that major defects in lymphocyte function affecting calcium signaling, nuclear factor of activated T cells activation, cytokine production, proliferation, apoptosis, and regulatory T‐cell development are present in SHR‐A3 and attributable to STIM1.

• Link: https://www.ahajournals.org/doi/10.1161/JAHA.119.014142