Elizabeth J Hennessy

University of Pennsylvania | UP · Institute for Translational Medicine and Therapeutics

A novel class of RNA molecule emerged from human transcriptome sequencing studies termed long non-coding RNAs. These RNA molecules differ from other classes of non-coding RNAs such as microRNAs in their sizes, sequence motifs and structures. Studies have demonstrated that long non-coding RNAs play a prominent role in the development and progression...

BACKGROUND Low-dose aspirin is widely used for the secondary prevention of cardiovascular disease. The beneficial effects of low-dose aspirin are attributable to its inhibition of platelet Cox (cyclooxygenase)-1–derived thromboxane A 2 . Until recently, the use of the Pf4 (platelet factor 4) Cre has been the only genetic approach to generating mega...

NSAIDs are amongst the most commonly used drugs by adults, but their use is complicated by an increased risk of adverse cardiovascular events that are consequent to suppression of cyclooxygenase-2 (COX-2) dependent prostaglandin (PG) formation, particularly prostacyclin (PGI 2 ). Amongst the mechanisms HDL may help to mediate cardiovascular risk is...

Optimal lung repair and regeneration is essential for recovery from viral infections including influenza A virus (IAV). We have previously demonstrated that acute inflammation and mortality induced by IAV is under circadian control. However, it is not known if the influence of the circadian clock persists beyond the acute outcomes. Here, we utilize...

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing safe in-person schooling has been a dynamic process balancing evolving community disease burden, scientific information, and local regulatory requirements with the mandate for education. Considerations include the health risks of SARS-CoV-2 infection and its...

Optimal lung repair and regeneration is essential for recovery from viral infections such as that induced by influenza A virus (IAV). We have previously demonstrated that lung inflammation induced by IAV is under circadian control. However, it is not known if the circadian clock exerts its influence on lung repair and regenerative processes indepen...

Inhibitors of mPges-1 are in the early phase of clinical development. Deletion of mPges-1 in mice confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing PGE2, but increasing biosynthesis of PGI2. In Ldlr-/- mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thro...

Since the COVID-19 pandemic swept across the globe, researchers have been trying to understand its origin, life cycle, and pathogenesis. There is a striking variability in the phenotypic response to infection with SARS-CoV-2 that may reflect differences in host genetics and/or immune response. It is known that the human epigenome is influenced by e...

Inhibitors of microsomal prostaglandin E synthase-1 (mPges-1) are in the early phase of clinical development. Deletion of mPges-1 confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing prostaglandin (PG) E2, but increasing biosynthesis of prostacyclin (PGI2). In hyperlipidemic mice, this last effect rep...

The human genome encodes thousands of long non-coding RNAs (lncRNAs), the majority of which are poorly conserved and uncharacterized. Here we identify a primate-specific lncRNA (CHROME), elevated in the plasma and atherosclerotic plaques of individuals with coronary artery disease, that regulates cellular and systemic cholesterol homeostasis. LncRN...

An inducible gene expression program is a hallmark of the host inflammatory response. Recently, long intergenic non-coding RNAs (lincRNAs) have been shown to regulate the magnitude, duration, and resolution of these responses. Among these is lincRNA-Cox2, a dynamically regulated gene that broadly controls immune gene expression. To evaluate the in...

Long non-coding RNAs (lncRNAs) are a class of regulatory RNAs capable of binding DNA, RNA, and/or protein to regulate transcriptional and epigenetic networks. Although thousands of lncRNAs have been identified, relatively few have been functionally characterized. Here we identify a primate-specific lncRNA, CHROME , encoded in a locus associated wit...

Long non-coding RNAs (lncRNAs) are a poorly understood class of regulatory RNAs, known to be highly species specific and capable of binding DNA, RNA, and/or protein to regulate transcriptional and epigenetic networks. Although thousands of lncRNAs have been identified in disease-related screens, only a few have been functionally characterized. Here...

Cholesterol homeostasis is fundamental to human health, and is thus, tightly regulated. MicroRNAs exert potent effects on biological pathways, including cholesterol metabolism, by repressing genes with related functions. We reasoned that this mode of pathway regulation could be exploited to identify novel genes involved in cholesterol homeostasis....

The discovery of microRNAs (miRNA) targeting gene pathways involved in HDL and LDL metabolism illuminated the potent role of non-coding RNAs in the regulation of cholesterol homeostasis. Long non-coding RNAs (lncRNA) have also been identified as crucial regulators of gene expression; however, few have been fully characterized. Here we report a nove...

Objective: Cholesterol homeostasis is fundamental to human health and is, thus, tightly regulated. MicroRNAs exert potent effects on biological pathways, including cholesterol metabolism, by repressing genes with related functions. We reasoned that this mode of pathway regulation could be exploited to identify novel genes involved in cholesterol h...

Long non-coding RNAs (lncRNAs) have emerged as important regulators of gene expression in diverse biological contexts. Although several thousand lncRNAs have been identified in humans, only a small number have been fully characterized. Here we identify a novel human lncRNA, linc-OSBPL6, that functions as a competing endogenous RNA to regulate cellu...

Macrophage autophagy is thought to be essential for protecting from atherosclerosis, and compromised autophagy in macrophages of the artery wall leads to a number of pathologic processes including activation of the inflammasome, defective efferocytosis, and impaired cholesterol metabolism. Autophagy of lipid droplets (LDs) or “lipophagy” catabolize...

Obesity and its co-morbidities, type 2 diabetes and cardiovascular disease, continue to increase and are a major threat to global health. Studies in mice and humans have shown that expansion of adipose tissue mass is closely associated with the recruitment of cells of the myeloid and lymphoid lineage, which gives rise to a state of chronic inflamma...

During obesity, macrophage accumulation in adipose tissue propagates the chronic inflammation and insulin resistance associated with type 2 diabetes. The factors, however, that regulate the accrual of macrophages in adipose tissue are not well understood. Here we show that the neuroimmune guidance cue netrin-1 is highly expressed in obese but not l...

High-density lipoprotein (HDL) is a natural nanoparticle that transports peripheral cholesterol to the liver. Reconstituted high-density lipoprotein (rHDL) exhibits anti-atherothrombotic properties and is being considered as a natural treatment for cardiovascular diseases. Furthermore, HDL nanoparticle platforms have been created for targeted deliv...

: It is now appreciated that over 90% of the human genome is comprised of non-coding RNAs that have the ability to affect other components of the genome and regulate gene expression. This has galvanized the development of RNA-based therapeutics for a myriad of diseases, including cancer, inflammatory conditions and cardiovascular disease. Several c...

Cellular lipid homeostasis is fundamental to human health. Recent studies indicate that microRNAs (miRNAs) play important roles in the post-transcriptional regulation of lipid metabolism genes. This is illustrated by the discovery, by our group and others, of miR-33 as a central regulator of multiple aspects of lipid metabolism, including cholester...

The complexity of miRNA-mediated pathway control has burgeoned since the discovery that miRNAs are found in the extracellular space and constitute a form of cell-cell communication. miRNAs have been found in plasma, urine and saliva and have recently been shown to be carried on lipoproteins. This has led to the proposal that circulating miRNAs may...

Although infections with virulent pathogens often induce a strong inflammatory reaction, what drives the increased immune response to pathogens compared to nonpathogenic microbes is poorly understood. One possibility is that the immune system senses the level of threat from a microorganism and augments the response accordingly. Here, focusing on cy...

Toll-like receptors (TLRs) modulate the expression of multiple microRNAs (miRNAs). Here, we report the down-regulation of miR-107 by TLR4 in multiple cell types. The miR-107 sequence occurs in an intron within the sequence encoding the gene for pantothenate kinase 1α (PanK1α), which is regulated by the transcription factor peroxisome proliferator-a...

There is a growing interest in the targeting of Toll-like receptors (TLRs) for the prevention and treatment of cancer, rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus (SLE). Several new compounds are now undergoing preclinical and clinical evaluation, with a particular focus on TLR7 and TLR9 activators as adjuvants...

The tumor suppressor PDCD4 is a proinflammatory protein that promotes activation of the transcription factor NF-kappaB and suppresses interleukin 10 (IL-10). Here we found that mice deficient in PDCD4 were protected from lipopolysaccharide (LPS)-induced death. The induction of NF-kappaB and IL-6 by LPS required PDCD4, whereas LPS enhanced IL-10 ind...

Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are central effectors of immune defence. During phagocytosis, particles are internalized into 'phagosomes', organelles from which immune processes such as microbial destruction and antigen presentation are initiated. Certain pathogens have evolved mechani...

Phagocyte recognition and clearance of bacteria play essential roles in the host response to infection. In an on-going forward genetic screen, we identify the Drosophila melanogaster scavenger receptor Croquemort as a receptor for Staphylococcus aureus, implicating for the first time the CD36 family as phagocytic receptors for bacteria. In transfec...