Rima Kaddurah-Daouk: Papers, Grants, and Patents

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Publications in the Metabolomics Field:

Rozen S., Cudkowicz M.E., Bogdanov M., Matson W.R., Kristal B.S., Beecher C., Harrison S., Vouros P., Flarakos J., Vigneau-Callahan K., Matson T.D., Newhall K.M., Beal M.F., Brown Jr R.H., and Kaddurah-Daouk R. (2005). Metabolomic analysis and signatures in motor neuron disease. Metabolomics 1(2): 101-108.

Fiehn O., Kristal B.S., Van Ommen B., Sumner L.W., Sansone S.A., Taylor C., Hardy N., Kaddurah-Daouk R.(2006). Establishing reporting standards for metabolomic and metabolomic studies: a call for participation. OMICS: A Journal of Integrative Biology 10(2): 158-163.

Castle A.L., Fiehn O., Kaddurah-Daouk R., Lindon, J.C. (2006). Metabolomics Standards Workshop and the development of international standards for reporting metabolomics experimental results. Brief Bioinform 7(2):159-165.

Kaddurah-Daouk R.(2006). Metabolic profiling of patients with schizophrenia. PLoS Med 3(8).

Paige L.A., Mitchell M.W., Krishnan K.R., Kaddurah-Daouk R, Steffens D.C. (2007). A preliminary metabolomic analysis of older adults with and without depression. Int J Geriatr Psychiatry 22(5): 418-423.

Kaddurah-Daouk R., McEvoy J., Baillie R.A., Lee D., Yao J.K., Doraiswamy P.M., Krishnan K.R. (2007). Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Mol Psychiatry 12(10): 934-945.

Kristal B.S., Shurubor Y.I., Kaddurah-Daouk R., Matson W.R. (2007). Metabolomics in the study of aging and caloric restriction. Methods in Molecular Biology 371: 393-409.

Kristal BS, Shurubor YI, Kaddurah-Daouk R, Matson WR (2007). Metabolomics in the study of aging and caloric restriction. Methods Mol Biol. 2007;371:393-409.

Sansone S.A., Fan T., Goodacre R., Griffin J.L., Hardy N.W., Kaddurah-Daouk R., Kristal B.S., Lindon J., Mendes P., Morrison N., Nikolau B., Robertson D., Sumner L.W., Taylor C., van der Werf M., van Ommen B., Fiehn O. (2007). The metabolomics standards initiative. Nat Biotechnol 8:846-848.

Fiehn O., Robertson D., Griffin J., van der Werf M., Nikolau B., Morrison N., Sumner L.W., Goodacre R., Hardy N.W., Taylor C., Fostel J., Kristal B., Kaddurah-Daouk R., Mendes P., van Ommen B., Lindon J.C., and Sansone S.A. (2007). The metabolomics standards initiative (MSI). Metabolomics 3(3): 175-178.

Kaddurah-Daouk R., Kristal B.S., Weinshilboum R.M.(2008). Metabolomics: A global biochemical approach to drug response and disease. Annu Rev Pharmacol Toxicol 48: 653-683.

Kaddurah-Daouk R. and Krishnan K.R. (2008). Metabolomics: A global biochemical approach to the study of central nervous system diseases. Neuropsychopharmacology 34(1): 173-86.

Yao J.K., Dougherty G.G. Jr., Reddy R.D., Keshavan M.S., Montrose D.M., Matson W.R., Rozen S., Krishnan R.R., McEvoy J., Kaddurah-Daouk R. (2009). Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. Mol Psychiatry. April 28:1-16.

Patkar A.A., Rozen S., Mannelli P., Matson W., Pae C.U., Krishnan R.R., Kaddurah-Daouk R. (2009). Alterations in tryptophan and purine metabolism in cocaine addiction: A metabolomic study. Psychopharmacology (Berl) 206(3): 479-489. 45.

Quinones MP, Kaddurah-Daouk R (2009). Metabolomics tools for identifying biomarkers for neuropsychiatric diseases. Neurobiol Dis. Aug;35(2):165-76.

Mannelli P., Patkar A., Rozen S., Matson W.R., Krishnan R., Kaddurah-Daouk R. (2009). Opioid use affects antioxidant activity and purine metabolism: Preliminary results. Hum Psychopharmacol 24(8):666-675.

Steffens D.C., Jiang W., Krishnan K.R., Karoly E.D., Mitchell M.W., O'Connor C.M., Kaddurah-Daouk R. (2010). Metabolomic differences in heart failure patients with and without major depression. J Geriatr Psychiatry Neurol 23(2):138-146.

Yao J.K., Dougherty G.G. Jr, Reddy R.D., Keshavan M.S., Montrose D.M.,Matson W.R., McEvoy J, Kaddurah-Daouk R. (2010). Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia. PLoS ONE 5(3): e9508.

Kaddurah-Daouk R., Baillie R.A., Zhu H., Zeng Z.B., Wiest M.M., Nguyen U.T., Watkins S.M., Krauss R.M. (2010). Lipidomic analysis of variation in response to simvastatin in the cholesterol and pharmacogenetics study. Metabolomics 6:191–201.

Fan T.W.M., Yuan P., Lane A.N., Higashi R.M., Wang Y., Hamidi A.B., Zhou R, Guitart Z., Chen G., Manji H.K., Kaddurah-Daouk R. (2010). Stable isotope-resolved metabolomic analysis of lithium effects on glial-neuronal metabolism and interactions. Metabolomics. 6: 165-179.

Ji Y, Hebbring S, Zhu H, Jenkins GD, Biernacka J, Snyder K, Drews M, Fiehn O, Zeng Z, Schaid D, Mrazek DA, Kaddurah-Daouk R*, Weinshilboum RM* (2011). Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics. Clin Pharmacol Ther. 2011 Jan;89(1):97-104.

Condray R, Dougherty GG, Keshavan MS, Reddy RD, Haas GL, Montrose DM, Matson WR, McEvoy J, Kaddurah-Daouk R, Yao JK (2011). 3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia. Int J Neuropsychopharmacol. Jan 28:1-12.

Kaddurah-Daouk R, Rozen S, Matson W, Han X, Hulette CM, Burke JR, Doraiswamy PM, Welsh-Bohmer KA (2011). Metabolomic changes in autopsy-confirmed Alzheimer's disease. Alzheimers Dement. Nov 12. [Epub ahead of print]

Grants and Funding for Metabolomics Research 2004-2011:

1. The ALS Association: Identification of Diagnostic Biomarkers and Therapeutic Targets for Amyotrophic Lateral Sclerosis.

2. NIEHS R21 and SBRI: Metabolic signatures in Amyotrophic Lateral Sclerosis.

3. NIDDK R21, Co-PI (Collaboration with Harvard Medical School): Metabolomic Analysis of Type 1 Diabetic Nephropathy.
The purpose of this study is to identify signatures that can predict type I diabetes at risk of developing kidney dysfunction.

4. Stanley Foundation: Metabolic Signatures in Schizophrenia.

5. NARSAD Foundation: Metabolic Signatures of Antipsychotic Drugs used in the Treatment of Schizophrenia.

6. NIMH R21, Collaboration: Tryptophan Metabolism, Genes, and Major Depression.

7. NIMH intramural program: Effects of lithium on astrocyte- neuron interactions.

8. BMS: Metabolic Signature for Aripiprazole and Risperidone.

9. Pfizer: Metabolic Signatures for Sertraline and Placebo.

10. R01 NS054008 NINDS/NIA: Metabolic Signatures in Alzheimer’s Disease.

11. R01 NS054008 Supplement to parent RO1: Metabolic Signatures in Alzheimer’s Disease.

12. Alzhiemer’s Drug Discovery Foundation: Metabolomics Markers of Preclinical and Early Alzheimer’s Disease.

13. HHSN271200900628P NIMH Collaboration with intramural program: Metabolomic Study of Reproductive Steroids and role in depression.

14. AS0059M10A10473, Stimulus funding Yale collaboration: 13C Measurement of GABA Synthesis in Depression.
Connecting central and peripheral metabolism and mapping of pathways implicated in depression.

15. R24 GM078233, NIGMS: Metabolomics Network for Drug Response Phenotype.
The current application is specifically designed to “integrate” metabolomics and pharmacogenomics to achieve a deeper understanding of the drug-response phenotype and to accelerate the establishment of genotype-phenotype correlations for drug response towards a personalized approach to therapy.

16. R24 GM078233 supplement NIGMS: Metabolomics Network for Drug Response Phenotype.

17. R01 MH084941-01A2, NIMH: Metabolic Signatures in Schizophrenia.

18. RC2 – GM092729-01: Stimulus Grand Funding: Pharmacometabolomics Network for Drug Response Phenotyping.
Integration of metabolomics with clinical pharmacology for mapping pathways implicated in variation in response to anti platelet and antihypertensive therapies.

19. R24 GM-088007-01A1, NIGMS Glue Grant Phase I: Pharmacometabolomics Research Network. Proposes the formation of a multi-institution research consortium involving centers of excellence in metabolomics and metabolomic bioinformatics, joined with centers of excellence in molecular pharmacology and pharmacogenomic science. The purpose is to create an environment in which a cooperative iterative process of hypothesis generation, testing and validation will be applied to achieve the union of metabolomic and pharmacologic science to create "Pharmacometabolomics".
 

Selected Issued Patents and Patent Applications:

7910301 Methods for drug discovery, disease treatment, and diagnosis using metabolomics March 22, 2011 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (Drug effects)

7682784 Methods for drug discovery disease treatment, and diagnosis using metabolomics March 23, 2010 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (Applications in Schizophrenia).

7682783 Methods for drug discovery, disease treatment, and diagnosis using metabolomics March 23, 2010 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (Applications in Depression)

7635556 Methods for drug discovery, disease treatment, and diagnosis using metabolomics December 22, 2009 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (Applications in Depression)

7556935 Induction of apoptosis by cellular stress July 7, 2009 The invention provides methods of screening to identify compounds that modulate the ability of a protein to translocate to the mitochondria when a cell is subjected to cellular stress. Such compounds can be useful to modulate the level of apoptosis in a cell.

7553616 Methods for drug discovery, disease treatment, and diagnosis using metabolomics June 30, 2009 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (Cancer applications).

7550260 Methods for drug discovery, disease treatment, and diagnosis using metabolomics June 23, 2009 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (Metabolic disorders)

7550258 Methods for drug discovery, disease treatment, and diagnosis using metabolomics June 23, 2009 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (general disease).

7329489 Methods for drug discovery, disease treatment, and diagnosis using metabolomics February 12, 2008 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (ALS disease).

7285573 Use of creatine or creatine analogs for the treatment of diseases of the nervous system October 23, 2007 The present invention relates to the use of creatine compounds including creatine, creatine phosphate or analogs of creatine, such as cyclocreatine, for treating diseases of the nervous system.

7186754 Use of creatine or creatine compounds for skin preservation March 6, 2007 The present invention relates to the use of creatine compounds such as, for example, creatine, creatine phosphate or analogs of creatine, such as creatine-pyruvate, creatine-ascorbate, cyclocreatine, 3 guanidinopropionic acid, guanidinoacetate, homocyclocreatine, guanidino benzoates for slowing aging of the skin.

7118862 Induction of apoptosis by cellular stress October 10, 2006 The invention provides methods of screening to identify compounds that modulate the ability of a protein to translocate to the mitochondria when a cell is subjected to cellular stress. Such compounds can be useful to modulate the level of apoptosis in a cell.

7005255 Methods for drug discovery, disease treatment, and diagnosis using metabolomics February 28, 2006 The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy. (ALS disease).

6720188 Methods and kits for the detection of arginine compounds April 13, 2004 Methods and kits for determine arginine compounds are discussed. The methods and kits of the invention can be used for the diagnosis of arginine compound associated disorders.

6706764 Use of creatine or creatine analogs for the treatment of diseases of the nervous system March 16, 2004 The present invention relates to the use of creatine compounds including creatine, creatine phosphate or analogs of creatine, such as cyclocreatine, for treating diseases of the nervous system.

6566086 Diagnostic kit for detecting creatine levels May 20, 2003 Methods for the detection of creatine compound levels in body fluid samples are discussed. Portable kits capable of determining creatine levels using non-invasive and visually detectable methods are also included.

6288124 Methods of inhibiting undesirable cell growth using an aminoguanidine compound September 11, 2001 The present invention provides for the use of aminoguanidines for prophylactic and/or therapeutic treatments of undesirable cell growth, e.g. tumors. The present invention provides methods of using aminoguanidines, optionally in combination with a hyperplastic inhibitory agents.

6242491 Use of creatine or creatine compounds for skin preservation June 5, 2001 The present invention relates to the use of creatine compounds such as, for example, creatine, creatine phosphate or analogs of creatine, such as creatine-pyruvate, creatine-ascorbate, cyclocreatine, 3 guanidinopropionic acid, guanidinoacetate, homocyclocreatine, guanidino benzoates for slowing aging of the skin.

6169115 Use of aminoguanidine analogs for the treatment of diseases of the nervous system January 2, 2001 The present invention relates to the use of aminoguanidine compounds for treating diseases of the nervous system. Aminoguanidine compounds can be used as therapeutically effective agents against a variety of diseases of the nervous system.

6075031 Use of creatine analogues and creatine kinase modulators for the prevention and treatment of glucose metabolic disorders. June 13, 2000 The present invention relates to the use of creatine compounds including cyclocreatine and creatine phosphate for treating or preventing a metabolic disorder consisting of hyperglycemia, insulin dependent diabetes mellitus, impaired glucose tolerance, hyperinsulinemia, insulin insensitivity.

5998457 Creatine analogues for treatment of obesity December 7, 1999 The present invention relates to the use of creatine compounds for treating or preventing a metabolic disorder related to body weight control such as obesity, and it's associated diseases in a patient experiencing said disorder.

5676978 Methods of inhibiting undesirable cell growth using a combination of a cyclocreatine compound an October 14, 1997 The present invention provides for the use of creatine compounds and hyperplastic inhibitory agents for prophylactic and/or therapeutic treatments of undesirable cell growth, e.g. tumors.

(WO 2007/127192) LIPIDOMIC APPROACHES TO DETERMINING DRUG RESPONSE PHENOTYPES IN CARDIOVASCULAR DISEASE 08.11.2007 G01N 33/92 PCT/US2007/009916 DUKE UNIVERSITY The present invention concerns the application of lipidomics to statin treatment for disorders such as cardiovascular disorders. Hence, the invention provides, among other things, a method of correlating a lipid profile with a positive or negative response to a statin treatment regimen by obtaining a lipid profile of a sample from a mammalian subject following commencement of the treatment regimen; and correlating the lipid profile in the sample with a positive or negative response to the treatment regimen. The invention further provides a method of correlating a lipid profile with a positive or negative response to a statin treatment

(WO 2007/050318) LIPIDOMICS APPROACHES FOR CENTRAL NERVOUS SYSTEM DISORDERS 03.05.2007 G01N 33/92 PCT/US2006/040026 DUKE UNIVERSITY The present invention has utilized the power of lipidomics to profile lipid metabolites and to characterize changes in lipid metabolism as they relate to CNS disorders. Lipidomic signatures can guide the development of diagnostic, prognostic and surrogate markers for CNS disorders; identification of new targets for drug design based on highlighted perturbed pathways; stratify patients with CNS disorders as to which pathways are impaired, and facilitate the determination of which patients with CNS disorders are candidates for a particular therapy, i.e. provide the tools for a personalized approach to therapy; identify which patients are responding or are developing side effects to a treatment.