Research Topics
Species | MARC KOPEL HELLERSTEINSummaryAffiliation: University of California Country: USA Publications
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Publications
Measurement of protein turnover rates by heavy water labeling of nonessential amino acidsRobert Busch
KineMed, Inc, Emeryville, CA 94608, USA
Biochim Biophys Acta 1760:730-44. 2006..In conclusion, 2H2O labeling permits sensitive, quantitative, operationally simple measurements of protein turnover in vivo by the rise-to-plateau approach, especially for proteins with slow constitutive turnover...
Whole-body glycolysis measured by the deuterated-glucose disposal test correlates highly with insulin resistance in vivoCarine Beysen
KineMed, Inc, Emeryville, California, USA
Diabetes Care 30:1143-9. 2007....
Mass isotopomer distribution analysis at eight years: theoretical, analytic, and experimental considerationsM K Hellerstein
Department of Nutritional Sciences, University of California at Berkeley, Berkeley, CA 94720, USA
Am J Physiol 276:E1146-70. 1999..In conclusion, MIDA remains the "equation for biosynthesis," but attention to potentially confounding factors and analytic performance is required for optimal application...
Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infectionMarc K Hellerstein
University of California, Berkeley, 119 Morgan Hall, Berkeley, California 94720 3104, USA
J Clin Invest 112:956-66. 2003..The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells...
Turnover of adipose components and mitochondrial DNA in humans: kinetic biomarkers for human immunodeficiency virus-associated lipodystrophy and mitochondrial toxicity?Marc K Hellerstein
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, 94720 3104, USA
Clin Infect Dis 37:S52-61. 2003..The results suggest that the kinetics of adipose-tissue components and mitochondrial DNA are measurable in vivo and that these measurements may prove useful as clinical biomarkers in patients with HIV/AIDS...
In vivo measurement of fluxes through metabolic pathways: the missing link in functional genomics and pharmaceutical researchMarc K Hellerstein
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, California 94720 3104, USA
Annu Rev Nutr 23:379-402. 2003..Several examples demonstrate that pathway flux results are often unexpected and not predicted by classic biochemistry or the expression of genes and proteins...
Measurement of mitochondrial DNA synthesis in vivo using a stable isotope-mass spectrometric techniqueMichelle L Collins
Graduate Group in Molecular and Biochemical Nutrition, University of California at Berkeley, Berkeley, CA 94720, USA
J Appl Physiol 94:2203-11. 2003..Use of this technique may allow improved understanding of the regulation of mitochondrial biogenesis in health and disease...
Exploiting complexity and the robustness of network architecture for drug discoveryMarc K Hellerstein
Department of Nutritional Sciences and Toxicology, 309 Morgan Hall, University of California, Berkeley, CA 94720
J Pharmacol Exp Ther 325:1-9. 2008..Pathway-based screening in vivo represents an alternative to the high attrition of the molecular target-based discovery paradigm...
A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: advantages of pathway-based discoveryMarc K Hellerstein
Department of Nutritional Sciences, 309 Morgan Hall, University of California at Berkeley, CA 94720, USA
Metab Eng 10:1-9. 2008..New approaches that take account of and are built on principles described by metabolic engineers are needed for the next generation of DDD...
Carbohydrate-induced hypertriglyceridemia: modifying factors and implications for cardiovascular riskMarc K Hellerstein
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, California 94720 3104, USA
Curr Opin Lipidol 13:33-40. 2002..Although some progress has been made in this field, the central public health issue - the net effect on cardiovascular risk - remains unresolved...
Stable isotope-mass spectrometric measurements of molecular fluxes in vivo: emerging applications in drug developmentMarc K Hellerstein
University of California at Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, CA 94720 3104, USA
Curr Opin Mol Ther 6:249-64. 2004..Several fundamental advantages of kinetic measurements are demonstrated. Measurement of molecular fluxes represents a powerful addition to drug development technology...
Effect of nucleoside reverse transcriptase inhibitors on mitochondrial DNA synthesis in rats and humansMichelle L Collins
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, CA 94720-3104, USA
J Acquir Immune Defic Syndr 37:1132-9. 2004....
AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiencyKathy Jaworski
Department of Nutritional Science and Toxicology, 220 Morgan Hall, University of California, Berkeley, California 94720, USA
Nat Med 15:159-68. 2009..AdPLA is a major regulator of adipocyte lipolysis and is crucial for the development of obesity...
Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colonSylvia Jeewon Kim
Graduate Group in Molecular and Biochemical Nutrition, University of California, Berkeley, 94720, USA
Am J Physiol Cell Physiol 286:C1464-73. 2004..Use of this approach may allow better understanding of mechanisms by which agents induce or protect against colon carcinogenesis...
Measurement of mouse vascular smooth muscle and atheroma cell proliferation by 2H2O incorporation into DNAAlice Chu
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720 7360, USA
Am J Physiol Cell Physiol 291:C1014-21. 2006..In summary, proliferation of VSMC and atheroma cells can be quantified reliably and sensitively without radioactivity and may be an informative biomarker in vascular hyperplastic diseases, including atherosclerosis...
Measurement of liver collagen synthesis by heavy water labeling: effects of profibrotic toxicants and antifibrotic interventionsJames L Gardner
Dept of Nutritional Sciences and Toxicology, Univ of California, Berkeley, CA 94720, USA
Am J Physiol Gastrointest Liver Physiol 292:G1695-705. 2007....
Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesityMaryam Ahmadian
Department of Nutritional Science and Toxicology, University of California, Berkeley, California, USA
Diabetes 58:855-66. 2009..To investigate the role of desnutrin in adipose tissue triacylglycerol (TAG) and fatty acid metabolism...
Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feedingElaine A Hsieh
Department of Nutritional Sciences and Toxicology, Morgan Hall, Rm. 309, University of California, Berkeley, CA 94720, USA
Am J Physiol Endocrinol Metab 288:E965-72. 2005..In summary, the CR effect on cell proliferation is potent, rapid, and reversible in several tissues, and an intermittent feeding pattern reproduces much of the effect in the absence of substantial CR...
Central memory CD8+ T cells appear to have a shorter lifespan and reduced abundance as a function of HIV disease progressionKristin Ladell
Division of Experimental Medicine and Department of Medicine, University of California, San Francisco, CA 94110, USA
J Immunol 180:7907-18. 2008....
Physiologic and pharmacologic factors influencing glyceroneogenic contribution to triacylglyceride glycerol measured by mass isotopomer distribution analysisJerry L Chen
Department of Nutritional Sciences and Toxicology, University of California-Berkeley, Berkeley, California 94720, USA
J Biol Chem 280:25396-402. 2005..low carbohydrate diet) or down-regulated in liver (e.g. fructose infusion). Additionally, stimulation of glyceroneogenesis by rosiglitazone in adipose tissue may be an important factor in the antilipolytic actions of thiazolidinediones...
Dose effects of modified alternate-day fasting regimens on in vivo cell proliferation and plasma insulin-like growth factor-1 in miceKrista A Varady
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, California 94720 3104, USA
J Appl Physiol 103:547-51. 2007..These findings confirm the beneficial effects of ADF-100% on cancer risk by decreasing cell proliferation and IGF-1 levels and suggest that modified ADF regimens comprising 25-50% CR on the fast day do not replicate these effects...
Alternate-day fasting and chronic disease prevention: a review of human and animal trialsKrista A Varady
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA 94720 3104, USA
Am J Clin Nutr 86:7-13. 2007..More research is required to establish definitively the consequences of ADF...
The effects of physiological adaptations to calorie restriction on global cell proliferation ratesMatthew D Bruss
Department of Nutritional Science and Toxicology, University of California at Berkeley, 94720 3104, USA
Am J Physiol Endocrinol Metab 300:E735-45. 2011..In addition, these data are consistent with the hypothesis that reduced cell proliferation rates could be useful as a biomarker of interventions that increase longevity...
Differential in vivo effects on target pathways of a novel arylpyrazole glucocorticoid receptor modulator compared with prednisoloneDonald J Roohk
Department of Nutritional Sciences and Toxicology, 309 Morgan Hall, University of California, Berkeley, CA 94720 3104, USA
J Pharmacol Exp Ther 333:281-9. 2010..Because multiple actions can be measured concurrently in a single animal, this method is a powerful systems approach for characterizing and differentiating the effects of ligands that bind nuclear receptors...
Do calorie restriction or alternate-day fasting regimens modulate adipose tissue physiology in a way that reduces chronic disease risk?Krista A Varady
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, California 94720 3104, USA
Nutr Rev 66:333-42. 2008..e., adipose tissue morphology, triglyceride metabolism, and adipokine release, and attempts to link these changes to indicators of chronic disease risk...
Calorie restriction increases fatty acid synthesis and whole body fat oxidation ratesMatthew D Bruss
Dept of Nutritional Sciences and Toxicology, Univ of California at Berkeley, Morgan Hall, Rm 309, Berkeley, CA 94720 3104, USA
Am J Physiol Endocrinol Metab 298:E108-16. 2010..This pattern may have implications for oxidative damage and disease risk...
Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restrictionKrista A Varady
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA 94720, USA
J Nutr Biochem 21:188-95. 2010..These findings indicate that ADF (both modified and true) produces similar beneficial modulations in body fat distribution and adiponectin levels as daily CR...
Alternate-day fasting reduces global cell proliferation rates independently of dietary fat content in miceKrista A Varady
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, California, USA
Nutrition 25:486-91. 2009..Accordingly, we examined the effects of 85% restriction on the fast day (ADF-85%) with an LF or HF background diet on proliferation rates of various tissues...
Dynamics of keratinocytes in vivo using HO labeling: a sensitive marker of epidermal proliferation stateElaine A Hsieh
Department of Nutritional Sciences and Toxicology, University of California-Berkeley, Berkeley, CA 94720, USA
J Invest Dermatol 123:530-6. 2004..Potential applications of this inherently safe method in humans might include studies of psoriasis, wound healing, chemopreventive agents, and caloric intake...
In vivo measurement of DNA synthesis rates of colon epithelial cells in carcinogenesisSylvia Jeewon Kim
Graduate Group in Molecular and Biochemical Nutrition, 309 Morgan Hall, University of California at Berkeley, CA 94720, USA
Biochem Biophys Res Commun 331:203-9. 2005..In conclusion, DNA synthesis rates of colon epithelial cells can be measured directly in vivo using stable-isotope labeling. Potential applications in humans include use as a biomarker for cancer chemoprevention studies...
Heavy water labeling of keratin as a non-invasive biomarker of skin turnover in vivo in rodents and humansGlen Lindwall
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA
J Invest Dermatol 126:841-8. 2006..In summary, 2H2O labeling of skin keratin represents a non-invasive approach for assessing skin turnover dynamics in pre-clinical models and in human subjects...
New stable isotope-mass spectrometric techniques for measuring fluxes through intact metabolic pathways in mammalian systems: introduction of moving pictures into functional genomics and biochemical phenotypingMarc K Hellerstein
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, 309 Morgon Hall, Berkeley, CA 94720 3104, USA
Metab Eng 6:85-100. 2004....
Delayed secretory pathway contributions to VLDL-triglycerides from plasma NEFA, diet, and de novo lipogenesis in humansAruna Vedala
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA 94720, USA
J Lipid Res 47:2562-74. 2006..The turnover time and sources of this pool differ in diabetic HPTG and nondiabetic HPTG, with potential therapeutic implications...
Pharmacological doses of dietary curcumin increase colon epithelial cell proliferation in vivo in ratsSylvia Jeewon Kim
Graduate Group in Molecular and Biochemical Nutrition, 309 Morgan Hall, University of California at Berkeley, CA 94720, USA
Phytother Res 21:995-8. 2007..05). Thus, pharmacological doses of curcumin increase CEC proliferation rate and pool size in normal rats. Reduction of CEC proliferation therefore cannot explain the proposed chemopreventive actions of curcumin in colon cancer...
In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cellsBradley T Messmer
Institute for Medical Research, North Shore-LIJ Research Institute, Manhasset, New York 11030, USA
J Clin Invest 115:755-64. 2005..A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration...
Emerging applications of kinetic biomarkers in preclinical and clinical drug developmentScott M Turner
KineMed Inc, Emeryville, CA 94608, USA
Curr Opin Drug Discov Devel 8:115-26. 2005..Stable isotope mass spectrometric technologies may provide a parallel efficiency for converting molecules into approved drugs with sufficient throughput and reproducibility to maintain pace with the modern engine for generating leads...
Heavy water labeling of DNA for measurement of cell proliferation and recruitment during primary murine lymph node responses against model antigensRobert Busch
KineMed Inc, 5980 Horton Street, Emeryville, CA 94608, USA
J Immunol Methods 337:24-34. 2008....
Centrosomal PKCbetaII and pericentrin are critical for human prostate cancer growth and angiogenesisJeewon Kim
Department of Chemical and Systems Biology, Stanford University, School of Medicine, Stanford, California 94305 5174, USA
Cancer Res 68:6831-9. 2008..Our results suggest that a PKCbetaII inhibitor such as betaIIV5-3 may be used to reduce prostate cancer growth by targeting both angiogenesis and tumor cell growth...
Discovery of novel hippocampal neurogenic agents by using an in vivo stable isotope labeling techniqueMahalakshmi Shankaran
KineMed, Inc, 5980 Horton Street, Suite 400, Emeryville, CA 94608, USA
J Pharmacol Exp Ther 319:1172-81. 2006..In conclusion, stable isotope labeling is an efficient, high-throughput in vivo method for measuring hippocampal progenitor cell proliferation that can be used to screen for novel neurogenic drugs...
Isolation of peripheral blood CD4(+) T cells using RosetteSep and MACS for studies of DNA turnover by deuterium labelingRobert Busch
KineMed, Inc, 5980 Horton St, Emeryville, CA 94608, USA
J Immunol Methods 286:97-109. 2004..Thus, both FACS and the new method isolate a similar mixture of long- and short-lived CD4(+) T cells. In practice, the RosetteSep/MACS method is simple, rapid, robust and capable of high throughput...
A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibilityMark P Keller
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53076, USA
Genome Res 18:706-16. 2008....
Development of a novel method for measuring in vivo breast epithelial cell proliferation in humansLisa M Misell
KineMed, Inc, 5980 Horton St, Suite 470, Emeryville, CA 94608, USA
Breast Cancer Res Treat 89:257-64. 2005..In summary, this novel method of measuring BEC proliferation in vivo holds promise for assessing the effects of anti-proliferative chemopreventive and chemotherapeutic agents...
CD4+ T cell kinetics and activation in human immunodeficiency virus-infected patients who remain viremic despite long-term treatment with protease inhibitor-based therapySteven G Deeks
Department of Medicine, University of California at San Francisco and San Francisco General Hospital, San Francisco, CA 94110, USA
J Infect Dis 185:315-23. 2002..These data indicate that partial virus suppression reduces CD4(+) cell turnover and activation, thereby resulting in sustained CD4(+) cell gains, and that measurements of T cell dynamics may provide an in vivo marker of viral virulence...
Measurement of brain microglial proliferation rates in vivo in response to neuroinflammatory stimuli: application to drug discoveryMahalakshmi Shankaran
KineMed Inc, Emeryville, California, USA
J Neurosci Res 85:2374-84. 2007..In conclusion, 2H2O labeling represents a relatively high-throughput, quantitative, and highly reproducible technique for measuring microglial proliferation, and is useful for screening and discovering novel anti-neuroinflammatory drugs...
The effect of dietary carbohydrate on genes for fatty acid synthase and inflammatory cytokines in adipose tissues from lean and obese subjectsLisa C Hudgins
The Rogosin Institute, New York, NY 10021, USA
J Nutr Biochem 19:237-45. 2008..However, the dietary responsiveness of the key enzyme controlling DNL in human adipose tissue, fatty acid synthase (FAS), is uncertain...
Measurement of cell proliferation by heavy water labelingRobert Busch
KineMed Inc, 5980 Horton Street, Emeryville, California 94608, USA
Nat Protoc 2:3045-57. 2007..The protocols enable definitive in vivo studies of the fraction or absolute number of newly divided cells and their subsequent survival kinetics in animals and humans...
Measurement of very low rates of cell proliferation by heavy water labeling of DNA and gas chromatography/pyrolysis/isotope ratio-mass spectrometric analysisJason N Voogt
KineMed Inc, 5980 Horton Street, Emeryville, California 94608, USA
Nat Protoc 2:3058-62. 2007..Indolent hematologic malignancies, such as chronic lymphocytic leukemia, and other relatively quiescent cells represent promising areas of application...
Measurement of pancreatic islet cell proliferation by heavy water labelingSongyuan Chen
KineMed Inc, Emeryville, CA 94608, USA
Am J Physiol Endocrinol Metab 293:E1459-64. 2007..In summary, heavy water labeling is a quantitative approach for measuring islet cell proliferation and testing therapeutic agents...
Thematic review series: patient-oriented research. Recent advances in liver triacylglycerol and fatty acid metabolism using stable isotope labeling techniquesElizabeth J Parks
Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, USA
J Lipid Res 47:1651-60. 2006..Patient-oriented research in conditions such as dyslipidemia and hepatic steatosis is made feasible by these scientific advances...
Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1aRobert H J Bandsma
Groningen University Institute for Drug Exploration, Center for Liver, The Netherlands
J Pediatr 140:256-60. 2002..These findings are potentially relevant for antihyperlipidemic treatment in patients with glycogen storage disease type 1a...
In vivo measurement of microtubule dynamics using stable isotope labeling with heavy water. Effect of taxanesPatrizia Fanara
KineMed, Inc, Emeryville, California 94608, USA
J Biol Chem 279:49940-7. 2004..This sensitive and quantitative in vivo assay of microtubule dynamics may prove useful for pre-clinical and clinical development of the next generation of MTPAs as anticancer drugs...
Research Grants
- DIRECTLY MEASURED T CELL DYNAMICS IN HIV PATHOGENESISMarc Hellerstein; Fiscal Year: 2000....
- DIRECTLY MEASURED T CELL DYNAMICS IN HIV PATHOGENESISMarc Hellerstein; Fiscal Year: 2004..Results have potential relevance to HIV-1 pathogenesis and therapy and to vaccination strategies. ..
- ADIPOCYTE TURNOVER AND METABOLISM IN HIV-1 LIPOATROPHYMarc Hellerstein; Fiscal Year: 2003....
- T-Cell Kinetics and Sources--Effects of HIV and TherapyMarc Hellerstein; Fiscal Year: 2007..J.M McCune. In summary, advances in technology now make it possible to directly address hypotheses concerning the role of thymic function in HIV-1 pathogenesis and the kinetic consequences of HIV-1 infection and therapies. ..
- Response to and signals of caloric restriction and intermittent feeding regimensMarc Hellerstein; Fiscal Year: 2009....
- T CELL KINETICS AND SOURCES--EFFECTS OF HIV AND THERAPYMarc Hellerstein; Fiscal Year: 2002....
- Response to and signals of caloric restriction and intermittent feeding regimensMARC KOPEL HELLERSTEIN; Fiscal Year: 2010....
