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Professor Rong Hai’s lab from the University of California, Riverside has created a new fusion protein that may be developed as a new vaccine to induce quick immune responses to protect people against SARS-CoV-2 infection and other coronavirus infections. The faster antibody response to SARS-CoV-2 is achieved with a fusion protein that combines the nucleoprotein (NP) of influenza virus and the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein. This new fusion protein is advantageous over current technology since it takes advantage of a patient’s preexisting immunity to the influenza virus nucleoprotein (NP) to elicit a faster protective antibody response after a single vaccine dose.  Fig 1: RBD specific IgG antibody responses induced by the UCR vaccination with sera collected at Day 14 post vaccination.  Unlike mice vaccinated with the NP/RBD fusion protein, mice infected with PR8 influenza virus and then vaccinated with PBS (black) or mice PBS infected and then PBS vaccinated (blue) did not express RBD neutralizing antibodies. Mice with preexisting immunity to PR8 had higher RBD specific antibody responses after NP/RBD vaccination (green) compared to mice that did not have preexisting immunity to PR8 (red).

Professors Xumei Chen and Meng Chen at the University of California, Riverside (UCR) have shown the miRNA156’s role in plant growth and productivity. As shown in Figure 1, miRNA156 acts in pathways involved with plant hormones such as auxin and brassinosteroids responsible for plant growth. Exogenous application of miRNA156 potentially in combination with exogenous auxins can be useful in a variety of horticultural contexts for their ability to increase auxin sensitivity and plant growth.    

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Professor Min Xue and his lab at the University of California, Riverside have developed a novel hydrophilic endocytosis-promoting peptide (EPP6) rich in hydroxyl groups with no positive charge that may be used for drug delivery purposes. This peptide is non-toxic and has been shown to transport a wide array of small-molecule cargos into a diverse panel of cells. It enables oral administration and absorption through the intestinal lining, and crosses the BBB in vivo. UCR EPP6 is advantageous over existing technologies since it is nontoxic, efficiently enables oral absorption and transport across the BBB.  Fig 1: A) Structure of the UCR EPP. B) Confocal images showing that EPP6 was able to transport different cargo molecules into the cells. C) Orally administered EPP6 is absorbed by the intestines, entering the blood circulation and reaching the brain.  

Researchers at the University of California, Riverside (UCR) in collaboration Nationwide Children’s Hospital  have developed and characterized small peptidomimetics that act as EphA4 agonists. Given ALS is a heterogeneous disease, astrocytes reprogrammed from the fibroblasts of patients with sporadic and SOD1-linked ALS (iAstrocytes) were cultured with MNs and the UCR/Nationwide EphA4 agonists.  As seen in Fig. 1, these small agonistic peptidomimetics decrease MN death in iAstrocytes derived from sporadic ALS (sALS) cells.     

Researchers from the University of California, Riverside have developed potent monoclonal antibody inhibitors with high MMP-12 selectivity.  These antibodies have applications in pharmaceuticals and biomedical sciences. Specifically, these antibodies may be developed as  therapies for inflammatory and neurological diseases. Fig 1: Inhibitory function of the MMP-12 antibodies LG4, LH6, and LH11 towards cdMMP-12. 

Prof. Mona Eskandari, whose research is known for seminal strides in experimental characterization and computational modeling of lung structural mechanics using novel techniques developed in her lab, has discovered a new method for measuring pulmonary function. It works by analyzing the change in temporal pressure while a patient is holding their breath. The measurement device is simple, comfortable and error-free for the patient to self-administer. Algorithms are used to transform the detailed lung data collection into actionable metrics for early detection capabilities for medical intervention and prevention. The discovery could provide more accessible, detailed, timely, and actionable data on lung function compared to conventional and currently used methods. Fig 1: The medical device prototype being tested in the laboratory  Fig 2: Preliminary data exhibiting detectable differences between several healthy and diseased mice lungs when utilizing the proposed new pulmonary function method

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Professor Jiayu Liao from the University of California, Riverside has identified small molecules that block  the Influenza B virus (IBV) from replicating by inhibiting the SUMOylation pathway. This IBV virus replication inhibition works by using the novel SUMOylation inhibitor, STE025, to inhibit the SUMOylation of the IBV M1 protein. SUMOylation also has active roles in the pathogenesis of several diseases, such as tumorigenesis, neurodegenerative diseases and infections, and as such, this technology could potentially be applied to these types of diseases as well. Fig 1: Cell death induced by IBV infection can be rescued by the UCR SUMOylation-specific inhibitor, STE025 (blue) compared to cells not exposed to IBV (green), and cells exposed to IBV without the UCR inhibitor (purple and red).  

Prof. Sean Cutler and colleagues at the University of California, Riverside have engineered a system and methods to induce gene expression in plants and organisms, including mammals, using the chemical compound mandipropamid. Using the PYR/PYL/HAB1 promoter system, the PYR1/HAB1 system is reprogrammed to be activiated with mandipropamid.  When the PYR1/HAB1 system dimerizes through chemical induced dimerization (CID) with mandipropamid, the system functions as a control switch for gene expression. This technology has been demonstrated to advantageously accelerate citrus breeding.  It may be applied to improve CAR T-cell therapy and agricultural crops. Fig 1: UCR’s PYR1/HAB1 system is programmed through chemical induced dimerization (CID) initiated by mandipropamid to function as a switch for agrochemical control of gene expression.  

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Professor Ameae Walker from the University of California, Riverside, Professor Srividya Swaminathan from the City of Hope Beckman Research Institute and their colleagues have developed a method for the prevention and treatment of B cell lymphomas. This technology works by systemically inhibiting expression of one form of the set of cell surface molecules that allow cells to respond to prolactin. This highly specific technology suppresses the deleterious downstream effects of prolactin that promote and sustain abnormal B cells. This invention is advantageous compared to existing technologies: all measures in mouse models and analysis of human cells suggest it is nontoxic and therefore will have significantly fewer, if any, side effects. It may also be used together with anti-psychotics that elevate prolactin. Finally, the technology includes a method for screening populations susceptible to development of DLBCL and other B lymphomas for early signs of disease. Antimaia Acts at Three Stages of B Lymphoma Development: 1) Antimaia, a splice modulating oligonucleotide (SMO) that decreases expression of the long form of the prolactin receptor, reduces the number of premalignant cells and the formation of abnormal antibody-producing cells. This also improves the symptomatology of autoimmune disease. 2) Antimaia prevents the conversion of premalignant to overt malignant B cells. 3) Antimaia kills B lymphoma cells. Antimaia works by reducing the number of long and intermediate form prolactin receptors (LF/IF PRLR) without effect on short receptors (SFPRLR). PRL, prolactin; Bcl2, B cell lymphoma 2; Myc, a proto-oncogene.

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