Jonathan C Cohen

Summary

Affiliation: University of Texas Southwestern Medical Center
Country: USA

Publications

  1. ncbi request reprint Molecular mechanisms of autosomal recessive hypercholesterolemia
    Jonathan C Cohen
    McDermott Center for Human Growth and Development, Center for Human Nutrition, Department of Internal Medicine, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, USA
    Curr Opin Lipidol 14:121-7. 2003
  2. pmc Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease
    Yongcheng Huang
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 286:37085-93. 2011
  3. pmc Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance
    Julia Kozlitina
    McDermott Center for Human Growth and Development, University of Texas, Southwestern Medical Center, Dallas, TX 75390 8591, USA
    Hepatology 53:467-74. 2011
  4. pmc A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis
    Shaoqing He
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 285:6706-15. 2010
  5. pmc Functional characterization of genetic variants in NPC1L1 supports the sequencing extremes strategy to identify complex trait genes
    Saleemah Fahmi
    Department of Molecular Genetics, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Hum Mol Genet 17:2101-7. 2008
  6. pmc Deletion of GPIHBP1 causing severe chylomicronemia
    Jonathan J Rios
    Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
    J Inherit Metab Dis 35:531-40. 2012
  7. pmc Emerging LDL therapies: Using human genetics to discover new therapeutic targets for plasma lipids
    Jonathan C Cohen
    Center for Human Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    J Clin Lipidol 7:S1-5. 2013
  8. pmc WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data
    Ming Yi
    Advanced Biomedical Computing Center, National Cancer Institute Frederick SAIC Frederick Inc, Frederick, MD 21702, USA
    BMC Bioinformatics 7:30. 2006
  9. ncbi request reprint Multiple rare alleles contribute to low plasma levels of HDL cholesterol
    Jonathan C Cohen
    Donald W Reynolds Cardiovascular Clinical Research Center and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
    Science 305:869-72. 2004
  10. pmc Endothelial lipase: direct evidence for a role in HDL metabolism
    Jonathan C Cohen
    McDermott Center for Human Growth and Development, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Clin Invest 111:318-21. 2003

Research Grants

  1. Genetic Determinants of Coronary Atherosclerosis
    Jonathan Cohen; Fiscal Year: 2009
  2. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 2002
  3. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 2001
  4. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 2000
  5. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 1999
  6. Genetic Determinants of Coronary Atherosclerosis
    Jonathan C Cohen; Fiscal Year: 2010

Collaborators

Detail Information

Publications68

  1. ncbi request reprint Molecular mechanisms of autosomal recessive hypercholesterolemia
    Jonathan C Cohen
    McDermott Center for Human Growth and Development, Center for Human Nutrition, Department of Internal Medicine, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, USA
    Curr Opin Lipidol 14:121-7. 2003
    ..This review summarizes the findings of new investigations into the pathophysiology and molecular genetics of ARH...
  2. pmc Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease
    Yongcheng Huang
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 286:37085-93. 2011
    ....
  3. pmc Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance
    Julia Kozlitina
    McDermott Center for Human Growth and Development, University of Texas, Southwestern Medical Center, Dallas, TX 75390 8591, USA
    Hepatology 53:467-74. 2011
    ..Neither APOC3 variant was associated with HOMA-IR in the Dallas Heart Study; this lack of association was confirmed in the ARIC study, even after the analysis was restricted to lean (BMI < 25 kg/m(2) ) individuals (n = 4399)...
  4. pmc A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis
    Shaoqing He
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 285:6706-15. 2010
    ..These data are consistent with PNPLA3-I148M promoting triglyceride accumulation by limiting triglyceride hydrolysis...
  5. pmc Functional characterization of genetic variants in NPC1L1 supports the sequencing extremes strategy to identify complex trait genes
    Saleemah Fahmi
    Department of Molecular Genetics, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Hum Mol Genet 17:2101-7. 2008
    ..Such sequence variations may explain a significant fraction of quantitative phenotypic variation in humans...
  6. pmc Deletion of GPIHBP1 causing severe chylomicronemia
    Jonathan J Rios
    Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
    J Inherit Metab Dis 35:531-40. 2012
    ..We describe the first neonate with complete GPIHBP1 deficiency due to homozygosity for a deletion of GPIHBP1...
  7. pmc Emerging LDL therapies: Using human genetics to discover new therapeutic targets for plasma lipids
    Jonathan C Cohen
    Center for Human Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    J Clin Lipidol 7:S1-5. 2013
    ....
  8. pmc WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data
    Ming Yi
    Advanced Biomedical Computing Center, National Cancer Institute Frederick SAIC Frederick Inc, Frederick, MD 21702, USA
    BMC Bioinformatics 7:30. 2006
    ..We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data...
  9. ncbi request reprint Multiple rare alleles contribute to low plasma levels of HDL cholesterol
    Jonathan C Cohen
    Donald W Reynolds Cardiovascular Clinical Research Center and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
    Science 305:869-72. 2004
    ..Thus, rare alleles with major phenotypic effects contribute significantly to low plasma HDL-C levels in the general population...
  10. pmc Endothelial lipase: direct evidence for a role in HDL metabolism
    Jonathan C Cohen
    McDermott Center for Human Growth and Development, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Clin Invest 111:318-21. 2003
  11. pmc Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels
    Jonathan C Cohen
    Donald W Reynolds Cardiovascular Clinical Research Center, Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9052, USA
    Proc Natl Acad Sci U S A 103:1810-5. 2006
    ....
  12. ncbi request reprint ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion
    Gregory A Graf
    McDermott Center for Human Growth and Development and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, 75390, USA
    J Biol Chem 278:48275-82. 2003
    ..Finally, adenoviral expression of G2 in the presence or absence of G5 or G8 failed to promote sterol excretion into bile. These experiments indicate that G5 and G8 function as obligate heterodimers to promote sterol excretion into bile...
  13. ncbi request reprint The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin-coated pits
    Rita Garuti
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 8591, USA
    J Biol Chem 280:40996-1004. 2005
    ..These results demonstrate that ARH must bind the LDLR tail and either clathrin or AP-2 to promote receptor clustering and internalization of LDL...
  14. ncbi request reprint Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and trafficking
    Gregory A Graf
    McDermott Center for Human Growth and Development and Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 75390, USA
    J Biol Chem 279:24881-8. 2004
    ..We conclude that the majority of the molecular defects in G5 and G8 that cause sitosterolemia impair transport of the sterol transporter to the cell surface...
  15. ncbi request reprint Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation
    Da Wei Zhang
    Department of Molecular Genetics, The Donald W Reynolds Cardiovascular Clinical Research Center, Howard Hughes Institute, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 282:18602-12. 2007
    ..As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded...
  16. ncbi request reprint Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia
    Christopher Jones
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 278:29024-30. 2003
    ..Taken together, these results are consistent with ARH playing a critical and specific role in LDLR endocytosis in the liver...
  17. ncbi request reprint The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits
    Peter Michaely
    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 279:34023-31. 2004
    ....
  18. pmc Purification and reconstitution of sterol transfer by native mouse ABCG5 and ABCG8
    Jin Wang
    Eugene McDermott Center for Human Growth and Development, Department of Internal Medicine, and the Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8591, USA
    Biochemistry 47:5194-204. 2008
    ..Both G5 and G8 have short but highly conserved cytoplasmic tails. The functional roles of these C-terminal regions were examined using an in vivo functional assay...
  19. pmc Disruption of LDL but not VLDL clearance in autosomal recessive hypercholesterolemia
    Christopher Jones
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    J Clin Invest 117:165-74. 2007
    ..The preservation of VLDL remnant clearance attenuates the phenotype of ARH and likely contributes to greater responsiveness to statins in ARH compared with FH...
  20. ncbi request reprint ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile
    Silvia Langheim
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Lipid Res 46:1732-8. 2005
    ..These results are consistent with the notion that increased biliary cholesterol secretion contributes to the reduction in fractional sterol absorption associated with G5G8 overexpression...
  21. ncbi request reprint Ezetimibe normalizes metabolic defects in mice lacking ABCG5 and ABCG8
    Liqing Yu
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Lipid Res 46:1739-44. 2005
    ..Together, these results indicate that pharmacological blockade of sterol absorption can ameliorate the deleterious metabolic effects of plant sterols even in the absence of G5 and G8...
  22. pmc Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion
    Liqing Yu
    McDermott Center for Human Growth and Development and Departments of Molecular Genetics and Biochemistry, The Howard Hughes Medical Institute and Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 99:16237-42. 2002
    ....
  23. pmc Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor
    Da Wei Zhang
    Department of Molecular Genetics, McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390 8591, USA
    Proc Natl Acad Sci U S A 105:13045-50. 2008
    ..Thus, domains in both the LDLR and PCSK9 that are not required for binding (or internalization) are essential for PCSK9-mediated degradation of the LDLR...
  24. ncbi request reprint Selective sterol accumulation in ABCG5/ABCG8-deficient mice
    Liqing Yu
    McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    J Lipid Res 45:301-7. 2004
    ..Thus, the accumulation of sterols other than cholesterol is sensed by the cholesterol regulatory machinery...
  25. pmc Genetic variation in ANGPTL4 provides insights into protein processing and function
    Wu Yin
    Eugene McDermott Center for Human Growth and Development, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 8591, USA
    J Biol Chem 284:13213-22. 2009
    ....
  26. pmc A feed-forward loop amplifies nutritional regulation of PNPLA3
    Yongcheng Huang
    Departments of Molecular Genetics and Internal Medicine, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 107:7892-7. 2010
    ....
  27. ncbi request reprint Sources of variability in genetic association studies: insights from the analysis of hepatic lipase (LIPC)
    Ralph V Shohet
    Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
    Hum Mutat 19:536-42. 2002
    ..Three novel LIPC polymorphisms were identified in the study (-1596insC, -2740A>G, and -2880G>C)...
  28. ncbi request reprint Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion
    Liqing Yu
    McDermott Center for Human Growth and Development, Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 280:8742-7. 2005
    ..Thus G5 and G8 are required to modulate biliary cholesterol secretion in response to cholate and diosgenin, but the choleretic effects of these two steroids are mediated by different mechanisms requiring FXR and PXR, respectively...
  29. ncbi request reprint Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8
    Liqing Yu
    McDermott Center for Human Growth and Development, Departments of Molecular Genetics and Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    J Biol Chem 278:15565-70. 2003
    ..Thus Abcg5 and Abcg8 are required for LXR agonist-associated changes in dietary and biliary sterol trafficking. These results establish a central role for ABCG5 and ABCG8 in promoting cholesterol excretion in vivo...
  30. ncbi request reprint Sterol transfer by ABCG5 and ABCG8: in vitro assay and reconstitution
    Jin Wang
    Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, 75390 8591, USA
    J Biol Chem 281:27894-904. 2006
    ..These studies indicate that G5 and G8 are sufficient for reconstitution of sterol transfer activity in vitro and provide the first demonstration that sterols are direct transport substrates of the G5 and G8 heterodimer...
  31. pmc Disruption of cholesterol homeostasis by plant sterols
    Chendong Yang
    Department of Molecular Genetics, McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas 75390 9046, USA
    J Clin Invest 114:813-22. 2004
    ..Stigmasterol also activated the liver X receptor in a cell-based reporter assay. These data indicate that selected dietary plant sterols disrupt cholesterol homeostasis by affecting two critical regulatory pathways of lipid metabolism...
  32. pmc Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote
    Zhenze Zhao
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, TX 75390, USA
    Am J Hum Genet 79:514-23. 2006
    ..The very low plasma level of LDL-C and apparent good health of this individual demonstrate that PCSK9 plays a major role in determining plasma levels of LDL-C and provides an attractive target for LDL-lowering therapy...
  33. pmc Identification of a VLDL-induced, FDNPVY-independent internalization mechanism for the LDLR
    Peter Michaely
    Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    EMBO J 26:3273-82. 2007
    ..Together, these experiments demonstrate that the LDLR has a very low-density lipoprotein (VLDL)-induced, FDNPVY-independent internalization mechanism...
  34. pmc Sequences in the nonconsensus nucleotide-binding domain of ABCG5/ABCG8 required for sterol transport
    Jin Wang
    Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, 75390 8591, USA
    J Biol Chem 286:7308-14. 2011
    ..Both the position and structural integrity of NBD2 are essential for sterol transport activity...
  35. ncbi request reprint Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands
    Chendong Yang
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, 75390, USA
    J Biol Chem 281:27816-26. 2006
    ..These observations are consistent with specific intermediates in the cholesterol biosynthetic pathway regulating lipid homeostasis through both the LXR and sterol response element-binding protein pathways...
  36. pmc Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL
    Stefano Romeo
    Donald W Reynolds Cardiovascular Clinical Research Center, the Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    Nat Genet 39:513-6. 2007
    ..Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history...
  37. pmc Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease
    Julia Kozlitina
    1 McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA 2
    Nat Genet 46:352-6. 2014
    ..Taken together, these data indicate that TM6SF2 activity is required for normal VLDL secretion and that impaired TM6SF2 function causally contributes to NAFLD. ..
  38. ncbi request reprint Sequence variations in PCSK9, low LDL, and protection against coronary heart disease
    Jonathan C Cohen
    Donald W Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    N Engl J Med 354:1264-72. 2006
    ..We examined the effect of DNA-sequence variations that reduce plasma levels of LDL cholesterol on the incidence of coronary events in a large population...
  39. pmc Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans
    Stefano Romeo
    Donald W Reynolds Cardiovascular Clinical Research Center and Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA
    J Clin Invest 119:70-9. 2009
    ..Thus, ANGPTL3, ANGPTL4, and ANGPTL5, but not ANGPTL6, play nonredundant roles in TG metabolism, and multiple alleles at these loci cumulatively contribute to variability in plasma TG levels in humans...
  40. ncbi request reprint High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr-/- mice
    Kenneth R Wilund
    Departments of Molecular Genetics and Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75290, USA
    J Lipid Res 45:1429-36. 2004
    ..These results demonstrate that increased expression of G5 and G8 attenuates diet-induced hypercholesterolemia in Ldlr-/- mice, resulting in a significant reduction in plasma levels of cholesterol and aortic atherosclerotic lesion area...
  41. pmc Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease
    Stefano Romeo
    Donald W Reynolds Cardiovascular Clinical Research Center, Eugene McDermott Center for Human Growth and Development, Dallas, TX 75390, USA
    Nat Genet 40:1461-5. 2008
    ..Thus, variation in PNPLA3 contributes to ancestry-related and inter-individual differences in hepatic fat content and susceptibility to NAFLD...
  42. pmc Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology
    Vered Molho-Pessach
    University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Hepatology 55:1139-45. 2012
    ..To our knowledge, the 32-year-old relative in this family represents the oldest asymptomatic patient with this disorder...
  43. pmc Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol
    Liqing Yu
    Department of Molecular Genetics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9046, USA
    J Clin Invest 110:671-80. 2002
    ....
  44. ncbi request reprint Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity
    Jeffrey D Browning
    Donald W Reynolds Cardiovascular Clinical Research Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9046, USA
    Hepatology 40:1387-95. 2004
    ..In conclusion, the significant ethnic and sex differences in the prevalence of hepatic steatosis documented in this study may have a profound impact on susceptibility to steatosis-related liver disease...
  45. pmc Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis
    Yan Wang
    Howard Hughes Medical Institute and Departments of Molecular Genetics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390
    Proc Natl Acad Sci U S A 110:16109-14. 2013
    ..Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis. ..
  46. pmc A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol
    Ingrid K Kotowski
    McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, 75390 9046, USA
    Am J Hum Genet 78:410-22. 2006
    ..These findings reveal that PCSK9 activity is a major determinant of plasma levels of LDL-C in humans and make it an attractive therapeutic target for LDL-C lowering...
  47. pmc Atypical angiopoietin-like protein that regulates ANGPTL3
    Fabiana Quagliarini
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 109:19751-6. 2012
    ..Inhibition of ANGPTL8 provides a new therapeutic strategy for reducing plasma lipoprotein levels...
  48. pmc Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR
    Yan Wang
    Department of Molecular Genetics, Howard Hughes Medical Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Lipid Res 53:1932-43. 2012
    ..Finally, the PCSK9-LDLR complex appears not to be transported by the canonical ESCRT pathway...
  49. pmc Indices of cholesterol metabolism and relative responsiveness to ezetimibe and simvastatin
    Susan G Lakoski
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390 9046, USA
    J Clin Endocrinol Metab 95:800-9. 2010
    ..Therefore, optimal prevention will require long-term LDL-C reduction, making it important to select the most effective agent for each individual...
  50. pmc Human fatty liver disease: old questions and new insights
    Jonathan C Cohen
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Science 332:1519-23. 2011
    ..Here, we discuss recent mechanistic insights into NAFLD, focusing primarily on those that have emerged from human genetic and metabolic studies...
  51. ncbi request reprint Functional asymmetry of nucleotide-binding domains in ABCG5 and ABCG8
    Da Wei Zhang
    McDermott Center for Human Growth and Development, The Department of Molecular Genetics, University of Texas Southwestern Medical Center, 75390, USA
    J Biol Chem 281:4507-16. 2006
    ..In contrast, mutations in key residues of the NBD formed by the Walker A and B motifs of G8 and the signature sequence of G5 did not affect sterol secretion...
  52. pmc A weighted false discovery rate control procedure reveals alleles at FOXA2 that influence fasting glucose levels
    Chao Xing
    Donald W Reynolds Cardiovascular Clinical Research Center, McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390 8591, USA
    Am J Hum Genet 86:440-6. 2010
    ..31 mg/dl per minor allele (p value = 2.2 x 10(-11)). This study reveals that there is a cache of less-frequent variants in GWAS arrays that can be identified via analytical approaches accounting for allele frequencies...
  53. ncbi request reprint Molecular mechanisms of autosomal recessive hypercholesterolemia
    Kenneth R Wilund
    McDermott Center for Human Growth and Development, Department of Molecular Genetics, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Hum Mol Genet 11:3019-30. 2002
    ..Residual LDLR function in cells that do not require ARH may explain why ARH patients have lower plasma LDL levels than do patients with homozygous familial hypercholesterolemia who have no functional LDLRs...
  54. pmc Genetic and metabolic determinants of plasma PCSK9 levels
    Susan G Lakoski
    Donald W Reynolds Cardiovascular Clinical Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Clin Endocrinol Metab 94:2537-43. 2009
    ..PCSK9 is present in human plasma, but the factors that contribute to differences in plasma concentrations of PCSK9 and how they impact on the levels of lipoproteins have not been well-characterized...
  55. ncbi request reprint No association between plasma levels of plant sterols and atherosclerosis in mice and men
    Kenneth R Wilund
    Donald W Reynolds Cardiovascular Clinical Research Center at Dallas, University of Texas Southwestern Medical Center at Dallas, Tex 75390 9046, USA
    Arterioscler Thromb Vasc Biol 24:2326-32. 2004
    ..We tested whether elevated plasma levels of plant sterols (sitosterol and campesterol) were associated with atherosclerosis in genetically modified mice and in middle-aged men and women...
  56. ncbi request reprint ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2
    Guocheng He
    McDermott Center for Human Growth and Development, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, 75290, USA
    J Biol Chem 277:44044-9. 2002
    ..These data are consistent with the hypothesis that ARH functions as an adaptor protein that couples LDLR to the endocytic machinery...
  57. pmc Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface
    Gregory A Graf
    McDermott Center for Human Growth and Development, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9046, USA
    J Clin Invest 110:659-69. 2002
    ..To our knowledge this is the first direct demonstration that trafficking of an ABC half-transporter to the cell surface requires the presence of its dimerization partner...
  58. pmc Dual roles for cholesterol in mammalian cells
    Fang Xu
    Center for Human Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 102:14551-6. 2005
    ....
  59. pmc Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis
    John Zhong Li
    Department of Molecular Genetics, Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA, USA
    J Clin Invest 122:4130-44. 2012
    ..The development of an animal model that recapitulates the metabolic phenotype of the allele in humans provides a new platform in which to elucidate the role of PNLPA3(I148M) in NAFLD...
  60. pmc Molecular biology of PCSK9: its role in LDL metabolism
    Jay D Horton
    Departments of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Trends Biochem Sci 32:71-7. 2007
    ..Although the mechanism of PCSK9 action is not yet clear, the protease provides a new therapeutic target to lower plasma levels of LDL and prevent CHD...
  61. pmc Identification by whole-genome resequencing of gene defect responsible for severe hypercholesterolemia
    Jonathan Rios
    McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
    Hum Mol Genet 19:4313-8. 2010
    ..These findings demonstrate that whole-genome (or exome) sequencing can be a valuable aid to diagnose genetic diseases, even in individual patients...
  62. pmc PCSK9: a convertase that coordinates LDL catabolism
    Jay D Horton
    Department of Internal Medicine, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    J Lipid Res 50:S172-7. 2009
    ....
  63. ncbi request reprint Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8
    Knut E Berge
    The Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390 9052, USA
    J Lipid Res 43:486-94. 2002
    ....
  64. ncbi request reprint Lipoprotein(a) and apolipoprotein(a) isoforms: no association with coronary artery calcification in the Dallas Heart Study
    Rudy Guerra
    Donald W Reynolds Center for Clinical Cardiovascular Research, Dallas, Tex, USA
    Circulation 111:1471-9. 2005
    ..It remains unclear whether elevated plasma levels of Lp(a) are an independent risk factor for coronary atherosclerosis in individuals of African descent...
  65. ncbi request reprint GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5
    Vidu Garg
    Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Rm NA8 124, Dallas, Texas 75390 9148, USA
    Nature 424:443-7. 2003
    ..These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5...
  66. pmc Lack of MEF2A mutations in coronary artery disease
    Li Weng
    US Department of Energy, Joint Genome Institute, Walnut Creek, California, USA
    J Clin Invest 115:1016-20. 2005
    ..These studies support that MEF2A mutations are not a common cause of CAD in white people and argue strongly against a role for the MEF2A 21-bp deletion in autosomal dominant CAD...
  67. pmc A common allele on chromosome 9 associated with coronary heart disease
    Ruth McPherson
    Division of Cardiology, University of Ottawa Heart Institute, Ottawa K1Y4W7, Canada
    Science 316:1488-91. 2007
    ..Homozygotes for the risk allele make up 20 to 25% of Caucasians and have a approximately 30 to 40% increased risk of CHD...
  68. ncbi request reprint Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels
    Len A Pennacchio
    Genome Sciences Department, MS 84 171, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA
    Hum Mol Genet 11:3031-8. 2002
    ..Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population...

Research Grants13

  1. Genetic Determinants of Coronary Atherosclerosis
    Jonathan Cohen; Fiscal Year: 2009
    ....
  2. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 2002
    ..These studies will help to determine the role of variation in hepatic lipase activity in determining plasma HDL concentrations, and LDL size distribution, two important risk factors for coronary artery disease. ..
  3. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 2001
    ..These studies will help to determine the role of variation in hepatic lipase activity in determining plasma HDL concentrations, and LDL size distribution, two important risk factors for coronary artery disease. ..
  4. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 2000
    ..These studies will help to determine the role of variation in hepatic lipase activity in determining plasma HDL concentrations, and LDL size distribution, two important risk factors for coronary artery disease. ..
  5. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 1999
    ..These studies will help to determine the role of variation in hepatic lipase activity in determining plasma HDL concentrations, and LDL size distribution, two important risk factors for coronary artery disease. ..
  6. Genetic Determinants of Coronary Atherosclerosis
    Jonathan C Cohen; Fiscal Year: 2010
    ....