Publications

HuProt Antibody Specificity: AA key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets.

• Link: https://www.nature.com/articles/nmeth.4632

HuProt PPI: We previously cloned the Ssp411 gene. We found that the Ssp411 protein is predominantly expressed in elongated spermatids in the rat testis in a stage-dependent manner. Although our findings strongly suggested that Ssp411 might play an important role in mammalian spermatogenesis, this hypothesis has not been studied.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S0304416517303938?via%3Dihub

HuProt Enzyme: Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses that cause widespread, acute febrile illnesses, notably microcephaly for fetuses of infected pregnant women. Detecting the viral cause of these illnesses is paramount to determine risks to patients, counsel pregnant women, and help fight outbreaks. A combined diagnostic algorithm for ZIKV and DENV requires Reverse transcription polymerase chain reaction (RT-PCR) and IgM antibody detection. RT-PCR differentiates between DENV and ZIKV infections during the acute phases of infection, but differentiation based on IgM antibodies is currently nearly impossible in endemic areas.

• Link: https://www.mcponline.org/article/S1535-9476(20)32274-X/fulltext#%20

HuProt Small Molecule: IgM antibody diversity induced by viral infection in teleost fish sera remains largely unexplored despite several studies performed on their transcript counterparts in lymphoid organs. Here, IgM binding to microarrays containing ~20,000 human proteins was used to study sera from carp (Cyprinus carpio) populations having high titers of viral neutralization in vitro after surviving an experimental infection with cyprinid herpes virus 3 (CyHV-3). The range of diversity of the induced antibodies was unexpectedly high, showing CyHV-3 infection-dependent, non-specific IgM-binding activity of a ~20-fold wider variety than that found in sera from healthy carp (natural antibodies) with no anti-CyHV-3 neutralization titers.

• Link: https://www.frontiersin.org/articles/10.3389/fimmu.2018.00039/full

HuProt PPI: It has been hypothesized that human cytomegalovirus (HCMV) infection, especially in monocyte and CD34 (+) myeloid cells, acts as a important regulator of immune system to promote inflammation in multiple autoimmune diseases. The aim of this study was to elucidate the HCMV gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of SLE patients and demonstrate the effect and mechanism of viral gene associated with SLE in mono-macrophages functions. Using two RNA-Seq techniques in combination with RT-PCR, 11 viral genes mainly associated with latent HCMV infection were identified in the PBMCs of SLE patients. Among these viral genes, US31 with previously unknown function was highly expressed in the PBMCs of SLE patients compared to healthy controls.

• Link: https://www.nature.com/articles/s41419-017-0122-4

The homozygous K108E mutation of interferon regulatory factor 8 (IRF8) is reported to cause dendritic cell (DC) and monocyte deficiency. However, more widespread immune dysfunction is predicted from the multiple roles ascribed to IRF8 in immune cell development and function. We sought to describe the effect on hematopoiesis and immunity of the compound heterozygous R83C/R291Q mutation of IRF8, which is present in a patient with recurrent viral infection, granuloproliferation, and intracerebral calcification.

• Link: https://www.jacionline.org/article/S0091-6749(17)31736-0/fulltext

Oral submucous fibrosis (OSF) is a chronic, insidious disease. The presence of autoantibodies in sera of OSF patients is the most characteristic and direct evidence of OSF being an autoimmune disease. To identify the specific autoantigens which could contribute to antibody production, the Human Proteome Microarrays composed of 19000 full-length unique proteins were employed. 45 proteins correlated with OSF were identified. To validate these results, we used ELISA to validate 28 OSF-associated autoantigens in extended samples. 8 autoantigens were positive in OSF serum with high frequency compared to the healthy controls.

• Link: https://www.oncotarget.com/article/20419/text/

HuProt Antibody Specificity: Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies. The immunological evolution of antibodies to mammalian glycans has not been studied.

• Link: https://www.cell.com/cell-reports/fulltext/S2211-1247(17)31029-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112471731029X%3Fshowall%3Dtrue#%20

HuProt PPI: Intravenous immunoglobulin (IVIg) is a complex mixture drug comprising diverse immunoglobulins and non–IgG proteins purified from the plasma of thousands of healthy donors. Approved IVIg products on the market differ regarding source of plasma, isolation process, and formulation. These products are used widely, and often interchangeably, for the treatment of immunodeficiency and autoimmune and inflammatory diseases, but their mechanisms of action in different indications are not well understood.

• Link: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181251

HuProt Review: Protein microarrays are platforms for studying protein-protein interactions and identifying disease-related self-antigens/autoantigens, which elicit an immune response in a high-throughput format. Protein arrays have been extensively used over the past two decades for several clinical applications. By using this platform, serum containing autoantibodies against potential self-antigens can be screened on proteome-wide arrays, harboring a large repertoire of full-length human proteins. Identification of such autoantigens can help deducing early diagnostic, as well as, prognostic markers in case of malignancies, autoimmune disorders, and other systemic diseases.

• Link: https://link.springer.com/protocol/10.1007/978-1-4939-7057-5_21