Hypoxia-inducible factor 1-alpha is a transcriptional regulator of the adaptive response to hypoxia. When activated under hypoxic conditions, it can turn on over 40 genes involved in a variety of physiological activities. The dysregulation or alteration by mutation can lead to pathophysiology in areas of energy metabolism, cancer, cell survival and tumor invasion.

Dr. Manuela Martins-Green’s UCR laboratory has developed a new assay to identify medicines that disrupt chronic wound biofilms in patients.  A patient’s wound biofilm is collected with a sterile swab and the bacteria collected from the swab are cultured and identified.  The bacteria are then used singly or in combination, to make a biofilm in 96 well plates to then be used for high throughput screening using a multitude of antibiotics, chemical and small molecules that may be tested alone or in combination for their ability to disperse the wound’s biofilm. Fig. 1 shows the biofilm cultures from chronic wound patient isolates. The biofilm is made more easily visible by staining with crystal violet. Fig. 2 Different concentrations of an antimicrobial drug ranging from 3 to 20 mg/ml were applied at 0, 6, 12, and 24 hours after the biofilm cultures were initiated. When applied at time zero the bacteria will not grow or form biofilm. This is akin to application after debridement. When applied after the biofilm has been formed it will dismantle the biofilm when used at the right concentrations. Akin to treating without debridement.  

The TBX18 (T-box 18) transcription factor is a key player in the formation of the sinoatrial node (SAN) formation during embryonic development.

The Casp8 gene encodes a cysteinyl aspartate protease that is an essential part of the caspase activation cascade initiated by death receptors but it is also involved in preventing death receptors, Toll-like receptors TLR3 and TLR4 and T-cell receptors from inducing necroptosis. Caspase-8 also is essential for mouse development.

Insulin gene enhancer protein ISL-1 or ISL1 transcription factor, LIM/homeodomain is a highly conserved gene. It binds to insulin gene enhancer sequences and is necessary for heart development

Insulin gene enhancer protein ISL-1 or ISL1 transcription factor, LIM/homeodomain is a highly conserved gene (UniProtKB-P61371). It binds to insulin gene enhancer sequences and is necessary for heart development. In addition, it plays an essential role in the gene regulatory network crucial for retinal ganglion cell (RGC) differentiation.

The Wnt gene family is composed of a large number of secreted glycoproteins involved in a wide variety of cell interactions ranging from early to adult stage that play a role in morphogenesis, paterning and development. In contrast to the Wnt/β-catenin signaling pathway which most Wnt proteins signal through, Wnt-11 signals via the Wnt/JNK pathway. A recent study demonstrates that the expression of secreted factor Wnt-ll is elevated in several types of cancer, including colorectal cancer (2019 R. M. Kypta et al.)

After an injury or neurological event, a patient’s rehabilitation requires long-term assessment and monitoring, especially in the upper extremities that are important for everyday tasks.UCI researchers have developed the Manumeter to quantitatively assess and log a patient’s hand movements without external therapist intervention.

MRI scans of patients/participants can be compared to template scans in order to identify differences or changes in brain anatomy. However, the templates that are used are typically of young brains, which lack the atrophy that naturally occurs in the aged brain. UCI researchers have developed a template for oldest old images (90+ age group) that takes into consideration the natural anatomical changes that can occur with aging.

Researchers at the University of California, Davis have developed a method for preparing a bacterial cell lysate that results in higher protein expression than existing cell-free systems. The new whole-cell lysate system comes with additional advantages, including the ability to synthesize protein from linear DNA, directly amenable to continuous or flow-based reaction, and compatibility with existing manufacturing workflow.

UCLA researchers in the Department of Bioengineering have developed systems and methods to produce single particle, monodisperse droplets for use in digital assays, targeted drug delivery, and theranostics.

HRas is a member of the Ras family of GTPases, which function as key regulatory proteins in cell differentiation, proliferation, and survival. Mutations in HRas are associated with several cancers, as well as Costello syndrome, a severe congenital disorder for which there is no cure. Therefore, there is significant interest in developing therapeutics which target HRas signaling. However, Ras proteins are challenging to target

Cell interactions are fundamental to biological processes. Microfluidics provides a reliable platform to study these intricate phenomena. The researchers have developed a microfluidic trapping array which efficiently pairs single cells in isolated compartments in an easy to operate manner to study cell-cell interaction, especially at single-cell level.

UCLA researchers in the School of Medicine have developed mutant polypeptides of the tissue factor pathway inhibitor-2 (TFPI-2) Kunitz domain 1 (KD1), which can serve as potent inhibitors of fibrinolysis.

Dishevelled (Dvl) proteins are important signaling components of both the canonical β-catenin/Wnt pathway, which controls cell proliferation and patterning, migration, differentiation, stem cell renewal and the planar cell polarity (PCP) pathway. Mammals share three Dishevelled (Dvl) family members and while the roles of Dvl1 and Dvl2 have been described previously, the functions of Dvl3 have remained an area of active research. The lack of Dvl3 in mice affects the formation of the heart, neural tube, and inner ear and that the defects in these tissues are much more severe when the mice are deficient in more than one Dvl family member, indicating redundant functions for these genes. Congenital heart disease affects approximately 75 in every 1,000 live human births, and approximately 30% of these diseases are due to disruptions in the outflow tract, the region affected in mice lacking Dvl genes.

The mouse Camp gene is an ortholog of the human gene CAMP, which encodes the precursor of cathelicidin antimicrobial peptide LL-37 (or CRAMP in mouse). Expressed mucosal epithelial cells, circulating neutrophils, and myeloid bone marrow cells, Camp is an essential part of the first line of defense against infection. In addition to antimicrobial activity, cathelicidin antimicrobial peptide plays a role in NK cell-mediated tumor growth suppression, and when secreted by neutrophils acts, as an attractant for monocytes, promoting wound healing or angiogenesis. Mouse CRAMP is implicated in adaptive immune response regulation and can interfere with TLR function via interactions with hyaluronan. Mice deficient in CRAMP are more susceptible to experimentally induced necrotic skin infection with Group A Streptococcus, urinary tract infection with uropathogenic E. coli, Pseudomonas aeruginosa infection, and meningococcal Neisseria meningitidis infection.

Miller–Dieker syndrome (MDS), or 17p13.3 deletion syndrome results in human neuronal migration disorders characterized by type 1 lissencephaly sequence (ILS), severe mental retardation and reduced life expectancy. The understanding of these syndromes is often incomplete and is the subject of active research. Researchers have demonstrated that the gene encoding 14-3-3ε (YWHAE), one of a family of ubiquitous phosphoserine/threonine–binding proteins, is always deleted in individuals with MDS. Mice deficient in Ywhae have defects in brain development and neuronal migration, similar to defects observed in mice heterozygous with respect to Pafah1b1.  Gene specific transcriptional activation or repression is regulated by a complex network of transcription factors designated the Myc/Max/Mad network. MNT (max binding protein) binds DNA and a heterodimer with MAX and represses transcription and acts as an antagonist of Myc-dependent transcriptional activation and cell growth. Described below are two mice strains that may be useful in studies of Miller-Dieker Lissencephaly Syndrome generated by the same researcher.

CAT2 is a membrane associated protein involved in the cellular uptake of cationic amino acids such as arginine, lysine and ornithine. CAT2 plays a regulatory role in the activation of macrophages. Arginine is a substrate for nitric oxide synthase (NOS) during the production of nitric oxide (NO). The release of NO by inflammatory cells contributes to the progression of diseases such as cancer, arthritis, inflammatory bowel disease, Crohn's disease, and atherosclerosis. CAT2 plays a role in controlling inflammation and IL-17 activation in an injury model of colitis.

Transgenic mouse models that develop spontaneous mammary adenocarcinomas have proven valuable in revealing molecular mechanisms underlying tumorigenesis and metastasis . Models target specific pathways depending on the transgene being expressed under the control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) or whey acid protein (WAP) mammary gland promoters and thereby replicate genetic defects in subsets of human tumors.

UCLA researchers in the Department of Microbiology, Immunology and Molecular Genetics have developed a novel method to produce short lentiviral vectors with tissue-specific expression, with a primary focus on lentiviral vectors for treating sickle cell disease and other disorders of hemoglobin.

UCLA researchers in the Department of Microbiology, Immunology and Molecular Genetics have developed a novel method to produce short lentiviral vectors with tissue-specific expression, with a primary focus on lentiviral vectors for treating sickle cell disease and other disorders of hemoglobin.

Ephrins and Eph receptor tyrosine kinases are cell-surface molecules that serve a multitude of functions in cell–cell communication in development, physiology, and disease.

The hyperpolarization activated nucleotide gated cation channel HCN4 is a pacemaker channel that is highly expressed in the sinoatrial node during development and in the adult. To better facilitate visualization of HCN4 expression, we generated mice with a nuclear localized (n) LacZ or H2BGFP knocked into the endogenous HCN4 locus and analyzed reporter expression in the heart during development.

These transgenic mice express an inducible version of cre recombinase mice under the direction of a Sox9 promoter. They are suitable for performing cre-recombination in pancreatic ductal cells and their progenitors.

Control of gene expression is a general approach to treat diseases where there is too much or too little of a gene product. However, while there are many methods which are available to downregulate the expression of messenger RNA transcripts, very few strategies can upregulate the endogenous gene product. The vast majority of gene regulatory drugs which are commercially available or being developed are designed to knockdown gene expression (i.e. siRNAs, miRNAs, anti-sense, etc.). There exist some methods to enhance gene expression, such as the delivery of messenger RNAs; although, therapeutic delivery of such large and charged RNA molecules is technically challenging, inefficient, and may not be practical. There are also classical gene therapy approaches where a gene product is delivered as viral-encoded products (AAV or lentivirus-packaged). However, these methods suffer from not being able to accurately reproduce the correct alternatively spliced isoforms in the right ratios in cells.