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Contact information Biosciences and Biotechnology Division Lawrence Livermore National Laboratory 7000 East Avenue, L-452 email: malfatti1@llnl.gov phone: 925-422-5732 |
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Education
Ph.D., Pharmacology/Toxicology, University of California, Davis, 2005
M.A., Biological Science, California State University, San Jose, 1992
B.S., Biological Science, California State University, San Jose, 1989
Research interests
Toxicology, Pharmacology, Biochemistry, Biomedical applications of accelerator mass spectrometry.
My research is focused on low-dose pharmacokinetic, metabolism, and tissue distribution studies of toxicants and potential drug leads using accelerator mass spectrometry in an effort to understand their mechanisms of action. We are also using a pharmacogenomics approach to understand the role of the microbiome on drug metabolism and disposition. We are utilizing AMS to quantify blood brain barrier penetration of novel drug leads to determine CNS efficacy.
Publications
1. Wang F, Zhang H, Ma AH, Yu W, Zimmermann M, Yang J, Hwang SH, Zhu D, Lin TY, Malfatti M, Turteltaub KW, Henderson PT, Airhart S, Hammock BD, Yuan J, de Vere White RW, Pan CX. (2018) COX-2/sEH Dual Inhibitor PTUPB Potentiates the Anti-tumor Efficacy of Cisplatin. Mol Cancer Ther., 17, 474-483. PMID: 29284644
2. Malfatti MA, Enright HA, Be NA, Kuhn EA, Hok S, McNerney MW, Lao V, Nguyen TH, Lightstone FC, Carpenter TS, Bennion BJ, Valdez CA. (2017) The biodistribution and pharmacokinetics of the oxime acetylcholinesterase reactivator RS194B in guinea pigs. Chem Biol Interact., 277, 159-167. PMID: 28941624
3. Enright HA, Falso MJS, Malfatti MA, Lao V, Kuhn EA, Hum N, Shi Y, Sales AP, Haack KW, Kulp KS, Buchholz BA, Loots GG, Bench G, Turteltaub KW. (2017) Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model. PLoS One. 2017 Aug 9;12(8): e0181996. PMID: 28792966
4. Bennion BJ, Be NA, McNerney MW, Lao V, Carlson EM, Valdez CA, Malfatti MA, Enright HA, Nguyen TH, Lightstone FC, Carpenter TS. (2017) Predicting a Drug's Membrane Permeability: A Computational Model Validated With in Vitro Permeability Assay Data. J Phys Chem B. 2017 May 25;121(20):5228-5237. PMID:28453293
5. Wang SS, Zimmermann M, Zhang H, Lin TY, Malfatti M, Haack K, Turteltaub KW, Cimino GD, de Vere White R, Pan CX, Henderson PT. (2017) A diagnostic microdosing approach to investigate platinum sensitivity in non-small cell lung cancer. Int J Cancer. 2017;141(3):604-613. PMID:28437852
6. Wang Y, Villalta PW, Peng L, Dingley K, Malfatti MA, Turteltaub KW, Turesky RJ. (2017) Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans. Chem Res Toxicol., 30(2), 705-714. PMID:28437852
7. Zimmermann M, Wang SS, Zhang H, Lin TY, Malfatti M, Haack K, Ognibene T, Yang H, Airhart S, Turteltaub KW, Cimino GD, Tepper CG, Drakaki A, Chamie K, de Vere White R, Pan CX, Henderson PT. (2017) Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice.Mol Cancer Ther. Feb;16(2):376-38. PMID:27903751
8. Enright HA, Malfatti MA, Zimmermann M, Ognibene T, Henderson P, Turteltaub KW. (2016) Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology.Chem Res Toxicol. 29(12), 1976-1986. PMID: 27726383
9. Scharadin TM, Zhang H, Zimmermann M, Wang S, Malfatti MA, Cimino GD, Turteltaub K, de Vere White R, Pan CX, Henderson PT. (2016) Diagnostic Microdosing Approach to Study Gemcitabine Resistance. Chem Res Toxicol. 29(11):1843-1848. PMID: 27657672
10. Malfatti MA, Kuhn EA, Turteltaub KW, Vickers SM, Jensen EH, Strayer L, Anderson KE. (2016) Disposition of the Dietary Mutagen 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline in Healthy and Pancreatic Cancer Compromised Humans. Chem Res Toxicol.2016 Mar 21;29(3):352-8. PMID:26918625
11. Sisi Wang; Hongyong Zhang; Tiffany M. Scharadin; Maike Zimmermann; Bin Hu; Amy Wang Pan; Ruth Vinall; Tzu-yin Lin; George Cimino; Patrick Chain; Cheryl Gleasner; Kim Mcmurry; Momchilo Vuyisich; Michael Malfatti; Kenneth Turteltaub; Ralph de Vere White; Chong-xian Pan; Paul Henderson (2016) Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer. PLoS ONE 11(1): e0146256. doi:10.1371/journal.pone.0146256. PMID:26799320
12. Jiang S, Pan AW, Lin TY, Zhang H, Malfatti M, Turteltaub K, Henderson PT, Pan CX. Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity. Chem Res Toxicol. 2015 Dec 21;28(12):2250-2. PMID:26544157
13. Cai H, Scott E, Kholghi A, Andreadi C, Rufini A, Karmokar A, Britton RG, Horner-Glister E, Greaves P, Jawad D, James M, Howells L, Ognibene T, Malfatti M, Goldring C, Kitteringham N, Walsh J, Viskaduraki M, West K, Miller A, Hemingway D, Steward WP, Gescher AJ, Brown K. Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice. Sci Transl Med. 2015 Jul 29;7(298). PMID:26223300
14. Nallathamby PD, Mortensen NP, Palko HA, Malfatti M, Smith C, Sonnett J, Doktycz MJ, Gu B, Roeder RK, Wang W, Retterer ST. (2015) New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies. Nanoscale.2015 Apr 21;7(15):6545-55
15. Madeen E, Corley RA, Crowell S, Turteltaub KW, Ognibene T, Malfatti M, McQuistan TJ, Garrard M, Sudakin D, Williams DE. (2015) Human in vivo Pharmacokinetics of [14C]Dibenzo[def,p]chrysene by Accelerator Mass Spectrometry Following Oral Micro-Dosing. Chem Res Toxicol.28(1) 126-134
16. Malfatti MA, Lao V, Ramos CL, Ong VS, Turteltaub KW. (2014) Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats. Antimicrob Agents Chemother. 2014 Nov;58(11):6477-83
17. Karen H. Dingley, Esther A. Ubick, John S. Vogel, Ted Ognibene, Michael Malfatti, Kristen Kulp, and Kurt W. Haack. (2014) “DNA Isolation and Sample Preparation for Quantification of Adduct Levels by Accelerator Mass Spectrometry,” In: Molecular Toxicology Protocols Methods in Molecular Biology, 2014; 1105, 147-157
18. He W, Luo J, Bourguet F, Xing L, Yi SK, Gao T, Blanchette C, Henderson PT, Kuhn E, Malfatti M, Murphy WJ, Cheng RH, Lam KS, Coleman MA. (2013) Controlling the diameter, monodispersity, and solubility of ApoA1 nanolipoprotein particles using telodendrimer chemistry. Protein Sci. Aug;22(8):1078-86
19. Malfatti, M. A., Palko, H. A., Kuhn, E. A., Turteltaub, K. W. (2012) Determining the pharmacokinetics and long-term biodistribution of SiO2nanoparticles in vivousing accelerator mass spectrometry. Nano Letters, 12, 5532-5538
20. Neuwirth C, Mosesso P, Pepe G, Fiore M, MalfattiM, Turteltaub K, Dekant W, Mally A. (2012) Furan carcinogenicity: DNA binding and genotoxicity of furan in rats in vivo. Mol Nutr Food Res.,56, 1363-1374.
21. Buchholz BA, Sarachine Falso MJ, Stewart BJ, Haack KW, Ognibene TJ, Bench G, Salazar Quintero GA, Malfatti MA, Kulp KS, Turteltaub KWet al: Bioanalytics for Human Microdosing. In Encyclopedia of Drug Metabolism and Interactions. John Wiley & Sons, Inc.; 2011
22. Benjamin J. Stewart, Graham Bench, Bruce A. Buchholz, Kurt W. Haack, Michael A. Malfatti, Ted J. Ognibene and Kenneth W. Turteltaub (2012) Accelerator Mass Spectrometry in Pharmaceutical Development. In Mass Spectroscopy Handbook, Lee, M.S. ed. John Wiley and Sons Inc. Hoboken, NJ. pp. 259-269.
23. Paul T. Henderson, Tao Li, Miaoling He, Hongyong Zhang, Michael Malfatti, Peter Grimminger, Kathryn Dannenberg, Ralph W. de Vere White, Kenneth W. Turteltaub, Chong-xian Pan(2011) A microdosing approach for characterizing formation and repair of carboplatin-DNA monoadducts and chemoresistance. International Journal of Cancer, 129, 1425-1434.
24. Pan C, Wang S, deVere White R, Gandara DR, Lara P, Li T, Mack P, Rodriguez-Fahrni A, Lee JS, Malfatti M, Turteltaub K, Henderson PT. (2011) A phase 0 microdosing trial of an in vivo assay for predicting chemoresistance to platinum. J Clin Oncol. 2011 May 20;29(15_suppl):2578.
25. isi Wang, Hongyong Zhang, Michael Malfatti, Ralph de Vere White, Primo Lara, Kenneth Turteltaub, Paul Henderson,Chong-xian Pan(2010). Gemcitabine causes minimal modulation of carboplatin-DNA monoadduct formation and repair in bladder cancer cells. Chemical Research inToxicology, 23, 1653-1655.
26. Chen, C., Ma, X., Malfatti, M., Krausz, K., Kimura, S., Felton, J., Idle, J., and Gonzalez, F. (2007) A Comprehensive Investigation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Metabolism in the Mouse Using a Multivariate Data Analysis Approach. Chemical Research in Toxicology, 20, 531-542.
27. Felton, J.S., Knize, M.G., Wu, R.W., Colvin, M.E., Hatch, F.T., and Malfatti, M.A. (2007) Mutagenic potency of food-derived heterocyclic amines. Mutation Research, 616, 90-94.
28. Ma, X. , Idle, J.R., Malfatti, M.A., Krausz, K.W., Nebert, D.W., Chen, C-S., Felton, J.S., Waxman, D.J., and Gonzalez, F.J. (2006) Mouse lung CYP1A1 catalyzes the metabolic activation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Carcinogenesis, 28, 732-737.
29. Malfatti, M.A., Dingley, K.H., Nowell, S., Ubick, E.A., Mulakken, N., Nelson, D., Lang, N.P., Felton, J.S., and Turteltaub, K.W. (2006) The urinary metabolite profile of the dietary Carcinogen PhIP is predictive of colon DNA adducts after a low dose exposure in humans. Cancer Research, 66, 10541-10547.
30. Felton, J.S. and Malfatti, M.A. (2006) What do diet-induced changes in phase I and II enzymes tell us about prevention from exposure to heterocyclic amine? Journal of Nutrition, 136, 2683S-2684S.
31. Malfatti, M.A. and Felton, J.S. (2006) Susceptibility to exposure to heterocyclic amines from cooked food: role of UDP-glucuronosyltransferase. In: Nutritional Genomics,Kaput, J. and Rodriguez, R.L eds. Wiley Interscience, Hoboken, N J. pp. 331-352
32. Malfatti, M.A., Ubick E.A. and Felton, J.S. (2005) The impact of glucuronidation on the bioactivation and DNA adduction of the cooked-food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in vivo. Carcinogenesis, 26, 2019-2028.
33. Wu, R.W., Malfatti, M.A., and Felton, J.S. (2005) Comparison of rat and human UDP-glucuronosyltransferase 1A1 expression on the mutagenicity and cytotoxicity of the cooked food carcinogen PhIP in CHO cells. The Ninth International Conference on Environmental Mutagens, San Francisco, CA, September 3-8 2005, In: Mutation Res. —Fundamental and Molecular Mechanisms of Mutagenesis577S, Abstract #114.
34. Malfatti, M.A., Wu, R.W., and Felton, J.S, (2005) The impact of UDP-glucuronosyltransferase 1A1 expression on the mutagenicity and metabolism of the cooked-food carcinogen PhIP in cellular and whole animal systems. American Association for Cancer Research 96thAnnual Meeting, Anaheim, CA, April 16-20, 2005. In: Proceedings of the 96thAnnual Meeting of the American Association for Cancer Research, Abstract #3888.
35. Malfatti, M.A., Wu, R.W., and Felton, J.S. (2005) The Effect of UDP-glucuronosyltransferase 1A1 expression on the Mutagenicity and Metabolism of the Cooked-Food Carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in CHO Cells. Mutation Research, 570, 205-214.
36. Malfatti, M.A., Wu, R.W., and Felton, J.S. (2004) The Impact of UDP-glucuronosyltransferase 1A1 expression on the Mutagenicity and Metabolism of the Cooked-Food Carcinogen PhIPin CHO Cells. UC Davis Cancer Center 10thAnnual Cancer Research Symposium. October 20-21, 2004, Abstract #23.
37. Felton, J.S., Knize, M.G., Malfatti, M.A., Lau, E., Colvin, M., Hatch, F., and Lightstone, F. (2004) Factors Determining Mutagenic Potency. Environmental Mutagen Society 35thAnnual Meeting, October 2-6, 2004, Abstract #52.
38. Malfatti, M.A. and Felton, J.S. (2004) Human UDP-glucuronosyltransferase 1A1 is the primary enzyme responsible for the N-glucuronidation of N-hydroxy-PhIP in vitro. Chemical Research in Toxicology, 17, 1137-1144.
39. Felton, J.S., Dingley, K.H., Fortson, S.L., Henderson, P.T., Knize, M.G., Kulp, K.S., Lang, N.P., Malfatti, M.A., Nelson, D.O., Salmon, C.P., and Wu, R.W. (2004) Heterocyclic amine intake, bioaccessibility, and mechanisms of biological effects. American Association for Cancer Research 95thAnnual Meeting, Orlando, Florida, March 27-31, 2004. In: Proceedings of the 95thAnnual Meeting of the American Association for Cancer Research, Abstract #3182.
40. Felton, J.S., Knize, M.G., Bennett, L.M., Malfatti, M.A., Colvin, M.E., and Kulp, K.S. (2004) Impact of environmental exposures on the mutagenicity/carcinogenicity of heterocyclic amines. Toxicology, 198, 135-145.
41. Malfatti, M.A. and Felton, J.S. (2002) The role of UDP-glucuronosyltrasferase activity in the metabolism of carcinogenic heterocyclic amines, and the potential effect on risk susceptibility. UC Davis Cancer Center 8thAnnual Cancer Research Symposium. September 19-20, 2002, Abstract #9.
42. Felton, J.S., Knize, M.G., Salmon, C.P., Malfatti, M.A., and Kulp, K.S. (2002) Human exposure to heterocyclic amine food mutagens/carcinogens: Relevance to breast cancer. Environmental and Molecular Mutagenesis, 39, 112-118.
43. Malfatti, M.A. and Felton, J.S. (2001) The N-glucuronidation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N-hydroxy-PhIP by specific human UDP-glucuronosyltransferases. Carcinogenesis, 22, 1087-1093.
44. Knize, M.G., Kulp, K.S., Malfatti, M.A., Salmon, C.P., and Felton, J.S. (2001) Liquid chromatography-tandem mass spectrometry method of urine analysis for determining human variation in carcinogen exposure. J. Chromatography, 914, 95-103.
45. Kulp, K.S., Knize, M.G., Malfatti, M.A., Salmon, C.P., and Felton, J.S. (2000) Identification of urine metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine following consumption of a single cooked chicken meal in humans. Carcinogenesis, 21, 2065-2072.
46. Malfatti, M.A., Kulp, K.S., Knize, M.G., Davis, C., Massengill, J.P., Williams, S., Nowell, S., MacLeod, S., Dingley, K.H., Turteltaub, K.W., Lang, N.P., and Felton, J.S. (1999) The identification of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) metabolites in humans. Carcinogenesis,20, 705-713.
47. Turteltaub, K.W., Dingley, K.H., Curtis, K.D., Malfatti, M.A., Turesky, R.J., Garner, R.C., Felton, J.S., and Lang N.P.(1999) Macromolecular adduct formation and metabolism of heterocyclic amines in humans and rodents at low doses. Cancer Letters, 143, 149-156.
48. Lang, N.P., Nowell, S., Malfatti, M.A., Kulp, K.S., Knize, M.G., Davis, C., Massengill, J., Williams, S., MacLeod, S., Dingley, K.H., Felton, J.S., and Turteltaub, K.W. (1999) In vivohuman metabolism of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Cancer Letters.143, 135-138.
49. Felton, J.S., Wu, R., Malfatti, M.A., and Knize, M.G. (1998) Evaluation of the role of acetyltransferases on heterocyclic amine genotoxicity. In Proceedings of the 1stInternational Workshop on Arylamine N-acetyltransferases.Cairns, Australia. October.
50. Felton, J.S., Malfatti, M.A., Knize, M.G., Salmon, C.P., Hopmans, E.C., and Wu, R.W. (1997) Health risks of heterocyclic amines. Mutation Research, 376, 37-41.
51. Malfatti, M.A., Connors M.S., Mauthe, R.J., and Felton, J.S. (1996) The capability of rat colon tissue slices to metabolize the cooked-food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Research, 56, 2550-2555.
52. Eades, D.M., Malfatti, M.A., and Felton, J.S. (1995) Analysis of PhIP metabolites by µLC-MS: Development of an ultra-sensitive method for low dose detection. The Sixth International Conference on Carcinogenic/Mutagenic N-substituted Aryl Compounds, Monterey, CA, November 4-8, 1995. In: Proceedings of the Sixth International Conference on Carcinogenic/Mutagenic N-substituted Aryl Compounds,ABS#105, 50.
53. Malfatti, M.A., Shen, N.H., Wu, R.W., Turteltaub, K.W., and Felton, J.S. (1995) A correlation of Salmonellamutagenicity with DNA adducts induced by the cooked-food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Mutagenesis, 10, 425-431.
54. Connors, M.S., Malfatti, M.A., and Felton, J.S. (1995) The metabolism of the cooked-food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in precision-cut rat liver slices. Chemico-Biological Interactions, 96, 185-202.
55. Malfatti, M.A., Buonarati, M.H., Turteltaub, K.W., Shen, N.H., and Felton, J.S. (1994) The role of sulfation and/or acetylation in the metabolism of the cooked-food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Salmonella typhimurium and isolated rat hepatocytes. Chemical Research in Toxicology, 7, 139-147.