Katrina Dipple | University of California, Los Angeles (original) (raw)

Papers by Katrina Dipple

Objective: Upper airway obstruction in a newborn with a craniofacial anomaly requires urgent mana... more Objective: Upper airway obstruction in a newborn with a craniofacial anomaly requires urgent management. While tracheostomy may be life saving in these circumstances, it may be associated with numerous morbidities. Distraction osteogenesis (DO) or lengthening of the mandible offers an alternative to tracheostomy with proper patient selection. Study Design: A ten-year review of neonates with upper airway obstruction at two

Molecular genetics and metabolism, 2003

Glycerol kinase (GK) is an enzyme at the interface of carbohydrate and fat metabolism. Mutations ... more Glycerol kinase (GK) is an enzyme at the interface of carbohydrate and fat metabolism. Mutations in the GK gene result in a rare inborn error of metabolism, GK deficiency (GKD), and at least one of these mutations (N288D) is associated with insulin resistance and diabetes mellitus. In an attempt to identify potential modifiers of the GKD phenotype, and to elucidate better the relationship between GKD and diabetes mellitus, we investigated the GK promoter. We examined the GK promoter using in silico methods, transient transfections of GK promoter-luciferase constructs in HepG2 hepatocellular carcinoma cells, and gel shift assays using liver nuclear extracts. We determined that the first 100 bp of the GK 5(') upstream region was sufficient for basal levels of transcription and that there was a functional HNF-4alpha binding site in the first 500 bp of the 5(') upstream region that was important for increased levels of GK expression in vitro. The involvement of both GK and HNF-4...

Molecular genetics and metabolism, 2002

Three older patients were diagnosed with systemic carnitine deficiency in childhood nearly a gene... more Three older patients were diagnosed with systemic carnitine deficiency in childhood nearly a generation ago and have together been treated for more than 50 patient years. Treatment improved tissue carnitine stores (proven in two) and eliminated most of the signs and symptoms of carnitine deficiency. All three have continued to respond to carnitine therapy and remain well except for the irreversible sequelae of the pretreatment illnesses. We demonstrate here that transformed lymphocytes from the first documented case of plasma membrane carnitine transporter deficiency fail to take up carnitine from the medium. The analysis of the cDNA of this patient and his parents revealed a homozygous frameshift mutation, 1027delT in exon 4. The resulting polypeptide terminates after amino acid 295. His parents are heterozygous for this mutation. The deletion resulted in predominately abnormal mRNA splicing with either a 13 or 19bp insertion between the junction of exons 3 and 4. The 13/19bp inser...

Advances in experimental medicine and biology, 1993

Advances in experimental medicine and biology, 1995

Advances in experimental medicine and biology, 1991

Single-gene disorders with "simple" Mendelian inheritance do not always imply that there will be ... more Single-gene disorders with "simple" Mendelian inheritance do not always imply that there will be an easy prediction of the phenotype from the genotype, which has been shown for a number of metabolic disorders. We propose that moonlighting enzymes (i.e., metabolic enzymes with additional functional activities) could contribute to the complexity of such disorders. The lack of knowledge about the additional functional activities of proteins could result in a lack of correlation between genotype and phenotype. In this review, we highlight some notable and recent examples of moonlighting enzymes and their possible contributions to human disease. Because knowledge and cataloging of the moonlighting activities of proteins are essential for the study of cellular function and human physiology, we also review recently reported and recommended methods for the discovery of moonlighting activities.

Molecular Genetics and Metabolism Reports, 2014

ABSTRACT Both adrenal catecholamines and steroids are known to be involved in the stress response... more ABSTRACT Both adrenal catecholamines and steroids are known to be involved in the stress response, immune function, blood pressure and energy homeostasis. The response to stress is characterized by the activation of the hypothalamus–pituitary–adrenal (HPA) axis and the sympathetic-adrenomedullary system, though the correlation with activation and development is not well understood. We evaluated the stress response of both cortisol and catecholamines during development in zebrafish. Zebrafish at two different stages of development were stressed in one of two different ways and cortisol and catecholamine were measured. Cortisol was measured by enzyme immune assay and catecholamine was measured by ELISA. Our results show that stress responses are delayed until after the synthesis of both cortisol and catecholamines. These observations suggest that the development of HPA axis may be required for the acquisition of the stress response for cortisol and catecholamines.

... 3 Judy Zhong, 2 Gevork Torosyan, 4 Sana Majid, 4 Brie Falkard, 4 Robert R. Kleinhanz ... 2 Da... more ... 3 Judy Zhong, 2 Gevork Torosyan, 4 Sana Majid, 4 Brie Falkard, 4 Robert R. Kleinhanz ... 2 Daria Estrada-Smith, 4 Charles R. Farber, 1 Susanna S. Wang, 4 Atila Van Nas, 4 ... 1 Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles ...

Molecular genetics and metabolism, 2015

Mathematical models of biological pathways facilitate a systems biology approach to medicine. How... more Mathematical models of biological pathways facilitate a systems biology approach to medicine. However, these models need to be updated to reflect the latest available knowledge of the underlying pathways. We developed a mathematical model of the insulin signal transduction pathway by expanding the last major previously reported model and incorporating pathway components elucidated since the original model was reported. Furthermore, we show that inputting gene expression data of key components of the insulin signal transduction pathway leads to sensible predictions of glucose clearance rates in agreement with reported clinical measurements. In one set of simulations, our model predicted that glycerol kinase knockout mice have reduced GLUT4 translocation, and consequently, reduced glucose uptake. Additionally, a comparison of our extended model with the original model showed that the added pathway components improve simulations of glucose clearance rates. We anticipate this expanded m...

The last years of research have been particularly dynamic in establishing the importance of pepti... more The last years of research have been particularly dynamic in establishing the importance of peptide deformylase (PDF), a protein of the N-terminal methionine excision (NME) pathway that removes formylmethionine from mitochondrial-encoded proteins. The genomic sequence of the human PDF gene is shared with the COG8 gene, which encodes a component of the oligomeric golgi complex, a very unusual case in Eukaryotic genomes. Since PDF is crucial in maintaining mitochondrial function and given the atypical short distance between the end of COG8 coding sequence and the PDF initiation codon, we investigated whether the regulation of the human PDF is affected by the COG8 overlapping partner. Our data reveals that PDF has several transcription start sites, the most important of which only 18 bp from the initiation codon. Furthermore, luciferase-activation assays using differently-sized fragments defined a 97 bp minimal promoter region for human PDF, which is capable of very strong transcriptional activity. This fragment contains a potential Sp1 binding site highly conserved in mammalian species. We show that this binding site, whose mutation significantly reduces transcription activation, is a target for the Sp1 transcription factor, and possibly of other members of the Sp family. Importantly, the entire minimal promoter region is located after the end of COG8's coding region, strongly suggesting that the human PDF preserves an independent regulation from its overlapping partner.

Objective: Upper airway obstruction in a newborn with a craniofacial anomaly requires urgent mana... more Objective: Upper airway obstruction in a newborn with a craniofacial anomaly requires urgent management. While tracheostomy may be life saving in these circumstances, it may be associated with numerous morbidities. Distraction osteogenesis (DO) or lengthening of the mandible offers an alternative to tracheostomy with proper patient selection. Study Design: A ten-year review of neonates with upper airway obstruction at two

Molecular genetics and metabolism, 2003

Glycerol kinase (GK) is an enzyme at the interface of carbohydrate and fat metabolism. Mutations ... more Glycerol kinase (GK) is an enzyme at the interface of carbohydrate and fat metabolism. Mutations in the GK gene result in a rare inborn error of metabolism, GK deficiency (GKD), and at least one of these mutations (N288D) is associated with insulin resistance and diabetes mellitus. In an attempt to identify potential modifiers of the GKD phenotype, and to elucidate better the relationship between GKD and diabetes mellitus, we investigated the GK promoter. We examined the GK promoter using in silico methods, transient transfections of GK promoter-luciferase constructs in HepG2 hepatocellular carcinoma cells, and gel shift assays using liver nuclear extracts. We determined that the first 100 bp of the GK 5(') upstream region was sufficient for basal levels of transcription and that there was a functional HNF-4alpha binding site in the first 500 bp of the 5(') upstream region that was important for increased levels of GK expression in vitro. The involvement of both GK and HNF-4...

Molecular genetics and metabolism, 2002

Three older patients were diagnosed with systemic carnitine deficiency in childhood nearly a gene... more Three older patients were diagnosed with systemic carnitine deficiency in childhood nearly a generation ago and have together been treated for more than 50 patient years. Treatment improved tissue carnitine stores (proven in two) and eliminated most of the signs and symptoms of carnitine deficiency. All three have continued to respond to carnitine therapy and remain well except for the irreversible sequelae of the pretreatment illnesses. We demonstrate here that transformed lymphocytes from the first documented case of plasma membrane carnitine transporter deficiency fail to take up carnitine from the medium. The analysis of the cDNA of this patient and his parents revealed a homozygous frameshift mutation, 1027delT in exon 4. The resulting polypeptide terminates after amino acid 295. His parents are heterozygous for this mutation. The deletion resulted in predominately abnormal mRNA splicing with either a 13 or 19bp insertion between the junction of exons 3 and 4. The 13/19bp inser...

Advances in experimental medicine and biology, 1993

Advances in experimental medicine and biology, 1995

Advances in experimental medicine and biology, 1991

Single-gene disorders with "simple" Mendelian inheritance do not always imply that there will be ... more Single-gene disorders with "simple" Mendelian inheritance do not always imply that there will be an easy prediction of the phenotype from the genotype, which has been shown for a number of metabolic disorders. We propose that moonlighting enzymes (i.e., metabolic enzymes with additional functional activities) could contribute to the complexity of such disorders. The lack of knowledge about the additional functional activities of proteins could result in a lack of correlation between genotype and phenotype. In this review, we highlight some notable and recent examples of moonlighting enzymes and their possible contributions to human disease. Because knowledge and cataloging of the moonlighting activities of proteins are essential for the study of cellular function and human physiology, we also review recently reported and recommended methods for the discovery of moonlighting activities.

Molecular Genetics and Metabolism Reports, 2014

ABSTRACT Both adrenal catecholamines and steroids are known to be involved in the stress response... more ABSTRACT Both adrenal catecholamines and steroids are known to be involved in the stress response, immune function, blood pressure and energy homeostasis. The response to stress is characterized by the activation of the hypothalamus–pituitary–adrenal (HPA) axis and the sympathetic-adrenomedullary system, though the correlation with activation and development is not well understood. We evaluated the stress response of both cortisol and catecholamines during development in zebrafish. Zebrafish at two different stages of development were stressed in one of two different ways and cortisol and catecholamine were measured. Cortisol was measured by enzyme immune assay and catecholamine was measured by ELISA. Our results show that stress responses are delayed until after the synthesis of both cortisol and catecholamines. These observations suggest that the development of HPA axis may be required for the acquisition of the stress response for cortisol and catecholamines.

... 3 Judy Zhong, 2 Gevork Torosyan, 4 Sana Majid, 4 Brie Falkard, 4 Robert R. Kleinhanz ... 2 Da... more ... 3 Judy Zhong, 2 Gevork Torosyan, 4 Sana Majid, 4 Brie Falkard, 4 Robert R. Kleinhanz ... 2 Daria Estrada-Smith, 4 Charles R. Farber, 1 Susanna S. Wang, 4 Atila Van Nas, 4 ... 1 Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles ...

Molecular genetics and metabolism, 2015

Mathematical models of biological pathways facilitate a systems biology approach to medicine. How... more Mathematical models of biological pathways facilitate a systems biology approach to medicine. However, these models need to be updated to reflect the latest available knowledge of the underlying pathways. We developed a mathematical model of the insulin signal transduction pathway by expanding the last major previously reported model and incorporating pathway components elucidated since the original model was reported. Furthermore, we show that inputting gene expression data of key components of the insulin signal transduction pathway leads to sensible predictions of glucose clearance rates in agreement with reported clinical measurements. In one set of simulations, our model predicted that glycerol kinase knockout mice have reduced GLUT4 translocation, and consequently, reduced glucose uptake. Additionally, a comparison of our extended model with the original model showed that the added pathway components improve simulations of glucose clearance rates. We anticipate this expanded m...

The last years of research have been particularly dynamic in establishing the importance of pepti... more The last years of research have been particularly dynamic in establishing the importance of peptide deformylase (PDF), a protein of the N-terminal methionine excision (NME) pathway that removes formylmethionine from mitochondrial-encoded proteins. The genomic sequence of the human PDF gene is shared with the COG8 gene, which encodes a component of the oligomeric golgi complex, a very unusual case in Eukaryotic genomes. Since PDF is crucial in maintaining mitochondrial function and given the atypical short distance between the end of COG8 coding sequence and the PDF initiation codon, we investigated whether the regulation of the human PDF is affected by the COG8 overlapping partner. Our data reveals that PDF has several transcription start sites, the most important of which only 18 bp from the initiation codon. Furthermore, luciferase-activation assays using differently-sized fragments defined a 97 bp minimal promoter region for human PDF, which is capable of very strong transcriptional activity. This fragment contains a potential Sp1 binding site highly conserved in mammalian species. We show that this binding site, whose mutation significantly reduces transcription activation, is a target for the Sp1 transcription factor, and possibly of other members of the Sp family. Importantly, the entire minimal promoter region is located after the end of COG8's coding region, strongly suggesting that the human PDF preserves an independent regulation from its overlapping partner.