A5045565015- Lipid metabolism and biosynthesis
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Plant responses to water stress
- Cancer, Hypoxia, and Metabolism
- Ion channel regulation and function
- Nitric Oxide and Endothelin Effects
- Neuroblastoma Research and Treatments
- Sunflower and Safflower Cultivation
- Sperm and Testicular Function
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- Angiogenesis and VEGF in Cancer
- Vanadium and Halogenation Chemistry
- Phosphodiesterase function and regulation
- Cannabis and Cannabinoid Research
- Immune Cell Function and Interaction
- Microbial Metabolic Engineering and Bioproduction
- Epigenetics and DNA Methylation
- Congenital heart defects research
University of Nebraska Medical Center
2022-2025
Mayo Clinic in Arizona
2017-2025
WinnMed
2020
Mayo Clinic
2016-2020
Grand Forks Human Nutrition Research Center
2013-2016
University of North Dakota
2014-2015
Lipid droplet (LD) catabolism in hepatocytes is mediated by a combination of lipolysis and selective autophagic mechanism called lipophagy, but the relative contributions these seemingly distinct pathways remain unclear. We find that inhibition lipolysis, or both resulted similar overall LD content dramatic differences morphology. Inhibition enzyme adipose triglyceride lipase (ATGL) large cytoplasmic LDs, whereas lysosomal caused accumulation numerous small LDs within cytoplasm degradative...
Hepatocytes metabolize energy-rich cytoplasmic lipid droplets (LDs) in the lysosome-directed process of autophagy. An organelle-selective form this (macrolipophagy) results engulfment LDs within double-membrane delimited structures (autophagosomes) before lysosomal fusion. Whether is an exclusive autophagic mechanism used by hepatocytes to catabolize unclear. It also unknown whether lysosomes alone might be sufficient mediate LD turnover absence autophagosomal intermediate. We performed...
The autophagic digestion of lipid droplets (LDs) through lipophagy is an essential process by which most cells catabolize lipids as energy source. However, the cellular machinery used for envelopment LDs during autophagy poorly understood. We report a novel function small Rab guanosine triphosphatase (GTPase) in recruitment adaptors required engulfment growing autophagosome. In hepatocytes stimulated to undergo autophagy, Rab10 activity amplified significantly, concomitant with its increased...
Alcohol consumption is a well-established risk factor for the onset and progression of fatty liver disease. An estimated 90% heavy drinkers are thought to develop significant steatosis. For these reasons, an increased understanding molecular basis alcohol-induced hepatic steatosis important. It has become clear that autophagy, catabolic process intracellular degradation recycling, plays key role in lipid metabolism. We have shown Rab7, small guanosine triphosphatase known regulate membrane...
Lipophagy is a central cellular process for providing the cell with readily utilized, high energy source of neutral lipids. Since its discovery over decade ago, we are just starting to understand molecular components that drive lipophagy, how it activated in response nutrient availability, and potential as therapeutic target disease. In this Cell Science at Glance article accompanying poster, first provide brief overview different structural enzymatic proteins comprise lipid droplet (LD)...
In liver steatosis (i.e. fatty liver), hepatocytes accumulate many large neutral lipid storage organelles known as droplets (LDs). LDs are important in the maintenance of energy homeostasis, but signaling mechanisms that stimulate LD metabolism poorly defined. adipocytes, catecholamines target β-adrenergic (β-AR)/cAMP pathway to activate cytosolic lipases and induce their recruitment surface. Therefore, goal this study was determine whether hepatocytes, like also undergo cAMP-mediated...
Abstract While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause deaths. Identification novel targetable pathways that contribute to tumor progression in could open new therapeutic options. The di-ganglioside GD2 is target FDA-approved antibody therapies neuroblastoma, but the role unexplored. Here, we show expressed small subpopulation cells subset patients and higher proportion metastatic tumors. Variable levels cell...
In this study, we examined the role of AKAP12, in endothelial cell motility, with a specific focus on AKAP12 variants AKAP12v1 and AKAP12v2. Previous work has shown that multivalent Akinase anchoring protein binds to PKA several other proteins regulating phosphorylation, is expressed at low levels most endothelia vivo but higher cells vitro. Here, found expression (HUVEC) cultures was density-dependent, being highest subconfluent lowest confluent cultures. also elevated wound edge wounded...
Rab32 is a small GTPase and molecular switch implicated in vesicular trafficking. also an A-Kinase Anchoring Protein (AKAP), which anchors cAMP-dependent Kinase (PKA) to specific subcellular locations specifies PKA phosphorylation of nearby substrates. Surprisingly, we found that form deficient binding (Rab32 L188P) relocalized away from the Golgi apparatus induced marked disruption organization, assembly, dynamics. Although L188P did not cause global defect activity, our data indicate...
ABSTRACT Epithelial cells, such as liver-resident hepatocytes, rely heavily on the Rab family of small GTPases to perform membrane trafficking events that dictate cell physiology and metabolism. Not surprisingly, disruption several proteins can manifest in metabolic diseases or cancer. Rab32 is expressed many secretory epithelial cells but its role cellular metabolism virtually unknown. In this study, we find associates with lysosomes regulates proliferation size Hep3B hepatoma HeLa cells....
Previous reports suggest that lipid droplets (LDs) in the hepatocyte can be catabolized by a direct engulfment from nearby endolysosomes (microlipophagy). Further, it is likely this process compromised chronic ethanol (EtOH) exposure leading to hepatic steatosis. This study investigates hepatocellular machinery supporting microlipophagy and EtOH-induced alterations with focus on small, endosome-associated, GTPase Rab5.
Clathrin-mediated endocytosis of transferrin (Tf) and its cognate receptor (TfR1) is a central pathway supporting the uptake trophic iron. It has generally been assumed that this constitutive process. However, we have reported non-receptor tyrosine kinase, Src, activated by Tf to facilitate internalization Tf-TfR1 ligand-receptor complex. As an extension these findings, tested whether subsequent trafficking steps might be regulated additional kinase-dependent cascades, observed significant...
Lipid droplets (LDs) are dynamic fat-storage organelles that interact readily with numerous cellular structures and organelles. A prominent LD contact site is degradative vesicles such as autophagosomes, lysosomes, autolysosomes, late endosomes. These contacts support lipid catabolism through the selective autophagy of LDs (i.e., lipophagy) or recruitment cytosolic lipases to surface lipolysis). However, LD–autophagosome serve additional functions beyond catabolism, including supply lipids...
Progesterone is an essential steroid hormone that required to initiate and maintain pregnancy in mammals serves as a metabolic intermediate the synthesis of endogenously produced steroids, including sex hormones corticosteroids. Steroidogenic luteal cells corpus luteum have tremendous capacity synthesize progesterone. These specialized are highly enriched with lipid droplets store substrate, which can be used for steroids. We recently reported hormone-stimulated progesterone by requires...
While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause deaths. Identification novel targetable pathways that contribute to tumor progression in could open new therapeutic options. The di-ganglioside GD2 is target FDA-approved antibody therapies neuroblastoma, but the role unexplored. Here, we show expressed small subpopulation cells subset patients and higher proportion metastatic tumors. Variable levels cell surface...
Steroidogenic tissues contain cytosolic lipid droplets that are important for steroidogenesis. Perilipin 2 (PLIN2), a structural coat protein located on the surface of in mammalian cells, plays crucial role regulating droplet formation and contributing to various cellular processes such as storage energy homeostasis. Herein, we examine PLIN2 progesterone synthesis bovine corpus luteum. Utilizing gene array databases Western blotting, have delineated expression pattern throughout follicular...
Lipid droplets (LDs) are fat‐storage organelles that play critical roles in energy homeostasis, but can excessively accumulate metabolic diseases such as obesity and fatty liver where hepatocytes become grossly engorged with excess lipid. The catabolism of LDs aids disease resolution occurs part by lipophagy, a form selective autophagy, the molecular vesicle trafficking events facilitate this process not fully understood. During autophagosomes thought to target prior fusion acidic lysosomes,...