Marie Migaud, Ph.D.

Marie Migaud, Ph.D.Professor, Department of Pharmacology, College of Medicine

Professor of Oncologic Sciences, Mitchell Cancer Institute

Abraham Mitchell Research Scholar, Mitchell Cancer Institute

Director of the Mass Spectroscopy Facilities, College of Medicine 

Adjunct Professor, Department of Chemical Engineering, College of Engineering

Adjunct Professor, Chemistry Department, College of Arts and Sciences

Phone: (251) 410-4938

mmigaud@health.southalabama.edu  

 

Overview

Synthetic organic chemist and chemical biologist with expertise in nucleoside, nucleotide, and dinucleotide chemistry and with focused interests on developing tools to probe vitamin Bs' chemical biology and its role in understanding diseases’ pathogenesis and pathophysiology. 

 

▼   Research Statement

My research interest resides in developing modular multidisciplinary strategies that seek to modulate the bioavailability of B-vitamin derived redox cofactors to interrogate biological systems while allowing the traceability of changes. Epigenetics evidence highlights the subtle orchestration of signaling and biosynthetic events controlled by the intracellular bioavailability of nicotinamide adenine dinucleotide (NAD, vitamin B3 derived, figure 1) and its phosphorylated and reduced forms (NAD(P)H), flavin adenine dinucleotide (FAD, vitamin B2 derived) and flavin mononucleotide (FMN), S-adenosyl methionine (SAM) and acyl-Co-enzyme A (Acyl-CoA, vitamin B5 derived).  The availability of these coenzymes is in turn regulated by metabolic events that modulate and are modulated by the availability of other cofactors; processes we seek to examine (Figure 1). Over the past 20 years, first in the UK and since 2016 at the University of South Alabama Mitchell Cancer Institute (MCI), my laboratory has developed a robust synthetic program that tackles the chemical limitations currently encountered in accessing B-vitamin derived species designed for “task-specific biological investigations”. To address the challenges of bioavailability, biodistribution, catabolism (Figure 2) and intracellularization, we develop strategies that allow for modular delivery. Key to our research efforts is the development of efficacious synthetic methodologies that allow atom-efficient scalable preparation of heteroaromatics, nucleos(t)ides and dinucleotides and give access to probes incorporating stable isotopes, fluorophores, and conjugatable containing moieties, designed to investigate the metabolic and signaling pathways regulated by B-vitamin-derived cofactors. At MCI and to complement our synthetic work, I have worked closely with biologists, nationally and internationally to manipulate and exploit the impact that these coenzymes’ metabolism and bioavailability have on aging and disease.

 

Figure 1: Tracing the metabolism of NAD precursors and how NAD is consumed in cells, tissues and animals.

Figure 1: Tracing the metabolism of NAD precursors and how NAD is consumed in cells, tissues and animals.

 

Figure 2: The fate of NAD(P)(H) (Biochemical Society Transactions (2019), 47(1), 131-147.)

Figure 2: The fate of NAD(P)(H) (Biochemical Society Transactions (2019), 47(1), 131-147.)

▼   Biography

Education

1986-1992
Diplome d’ingenieur Chimiste, Ecole Superieure de Chimie Organique et Minerale (ESCOM) (eq. BSc in Chemistry + MEng), Paris, FR

 

Postgraduate Training and Research Fellowship Appointments

1991-1996 
Postgraduate PhD. Department of Chemistry, Michigan State University, East   Lansing, MI, USA 

 

1996-1998 
Postdoctoral fellow, School of Pharmacy University of Bath, England, UK 

 

1998-2000
Postdoctoral fellow, Chemistry Department, University of Oxford, England, UK

 

Faculty Appointments

April 2020-  
Adjunct Professor, Department of Chemical Engineering, College of Engineering, University of South Alabama, AL, USA

 

Aug 2019- 
Professor of Pharmacology, Department of Pharmacology, College of Medicine, Mobile, AL, USA

 

April 2019-
Director of the Mass Spectroscopy Facilities, College of Medicine, Mobile, AL, USA

 

April 2017-
Adjunct Professor, Chemistry Department, College of Arts and Sciences, University of South Alabama, AL, USA

 

Nov 2016- 
Professor of Oncologic Sciences, University of South Alabama, Mitchell Cancer Institute, Mobile, AL, USA

 

Nov 2016- 
Abraham Mitchell Research Scholar, Mitchell Cancer Institute, USA, Mobile, AL, USA

 

2015-2016  
Levitt Visiting Faculty Professor; Department of Biochemistry; Carver College of Medicine, University of Iowa, Iowa city, IA, USA. Sabbatical

 

2010-2016 
Associated then Full Professor in Medicinal and Biological Chemistry; School of Pharmacy, Queen’s University Belfast, QUB, Belfast, Northern Ireland, UK

 

2000-2010  
Lecturer (Assistant Professor), Senior lecturer (Tenured Assistant Professor) then Reader (Tenured Associate Professor) in Organic and Biological Chemistry, School of Chemistry and Chemical Engineering and the Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, Northern Ireland, UK

 

▼   Areas of expertise
Organic Synthesis
Organic Synthesis; Nucleoside, Nucleotides, Dinucleotides, Phosphate Chemistry; Ionic Liquids in Organic Chemistry; Mechanochemistry

 

Chemical Biology
Isotopic and Fluorescent Tracing; Metabolomics

 

Drug Delivery
Nanoparticle generation and characterization 

 

Oncological Chemical Biology
Cell metabolism; Mitochondrial Dysfunction

 

Micronutrition in cancer
Metabolic and Signaling coenzymes (NAD; FAD; SAM; Acyl-CoA)-biosynthetic pathways in cancer

 

▼   Recent Publications
  1. An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides. Trisha J. Grevengoed, Samuel A. J. Trammell, Jens S. Svenningsen, Mikhail Makarov, Thomas Svava Nielsen, Jens C. B. Jacobsen, Philip C. Calder, Marie E. Migaud, Benjamin Cravatt, and Matthew P. Gillum. J Clin Invest. 2021. https://doi.org/10.1172/JCI143861.
  2. Salvaging the endothelium in acute respiratory distress syndrome: a druggable intersection between TLR4 and NAD+ signalling. Lee JY, Stevens RP, Migaud M, et al.  Eur Respir J 2021; 0: 2004588 [https://doi.org/10.1183/13993003.04588-2020].
  3. Kropotov, A.; Kulikova, V.; Nerinovski, K.; Yakimov, A.; Svetlova, M.; Solovjeva, L.; Sudnitsyna, J.; Migaud, M.E.; Khodorkovskiy, M.; Ziegler, M.; et al. Equilibrative Nucleoside Transporters Mediate the Import of Nicotinamide Riboside and Nicotinic Acid Riboside into Human Cells. Int. J. Mol. Sci. 2021, 22, 1391. https://doi.org/10.3390/ijms220313911.  
  4. Hayat F, Sonavane M, Makarov MV, Trammell SAJ, McPherson P, Gassman NR, Migaud ME. The Biochemical Pathways of Nicotinamide-Derived Pyridones. Int J Mol Sci. 2021 Jan 24;22(3) PubMed PMID: 33498933. 
  5. SLC25A51 is a mammalian mitochondrial NAD+ transporter. Luongo TS, Eller JM, Lu MJ, Niere M, Raith F, Perry C, Bornstein MR, Oliphint P, Wang L, McReynolds MR, Migaud ME, Rabinowitz JD, Johnson FB, Johnsson K, Ziegler M, Cambronne XA, Baur JA. Nature. 2020 Sep 9. doi: 10.1038/s41586-020-2741-7. 
  6. Metabolomics to Predict Antiviral Drug Efficacy in COVID-19. Marie Migaud, Sheetal Gandotra, Hitendra S Chand, Mark N Gillespie, Victor J Thannickal, Raymond J Langley, 2021, PMID: 32574504 PMCID: PMC7462337 Am J Respir Cell Mol Biol.  2020 Sep;63(3):396-398. doi: 10.1165/rcmb.2020-0206LE.
  7. Nicotinamide riboside-amino acid conjugates that are stable to purine nucleoside phosphorylase. Hayat F, Migaud ME. Org Biomol Chem. 2020 Apr 15;18(15):2877-2885. doi: 10.1039/d0ob00134a. PMID: 32236231
  8. Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity, Anna Wilk, Faisal Hayat, Richard Cunningham, Jianfeng Li, Silvia Garavaglia, Leila Zamani, Davide M. Ferraris, Peter Sykora, Joel Andrews, Jennifer Clark, Amanda Davis, Laurent Chaloin, Menico Rizzi, Marie Migaud & Robert W. Sobol, Sci Rep 10, 651 (2020). https://doi.org/10.1038/s41598-020-57506-9. 
  9. A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor, J. Giroud-Gerbetant, M. Joffraud, M. Pilar Giner, A. Cercillieux, S. Bartova, M. V Makarov, R. Zapata-Pérez, J.L Sánchez-García, R.H Houtkooper, M.E Migaud, S. Moco, C. Canto Molecular Metabolism, Vol. 30, December 2019, Pages 192-202; DOI: 10.1016/j.molmet.2019.09.013.  
  10. Scalable syntheses of traceable ribosylated NAD+ precursors. Makarov, V.M.; Harris, N.; Rodrigues, M.; Migaud, M.E. Organic & Biomolecular Chemistry, 2019, DOI: 10.1039/C9OB01981B.  
  11. Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications. Hill M, Twigg M, Sheridan EA, Hardy JG, Elborn JS, Taggart CC, Scott CJ, Migaud ME. Pharmaceutics. 2019 Aug 2;11(8). pii: E379. doi: 10.3390/pharmaceutics11080379. PMID: 31382357. 
  12. Reply to: Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter. Grozio A, Mills K, Yoshino J, Bruzzone S, Sociali G, Tokizane K, Lei HC, Sasaki Y, Migaud M, Imai SI. Nat Metab. 2019 Jul;1(7):662-665. doi: 10.1038/s42255-019-0086-z. Epub 2019 Jul 12. PMID: 32694650 No abstract available. PMID: 32906142.
  13. Dihydroxyacetone Exposure Alters NAD(P)H and Induces Mitochondrial Stress and Autophagy in HEK293T. Cells, Smith KR, Hayat F, Andrews JF, Migaud ME, Gassman NR. Chem Res Toxicol. 2019 Aug 19;32(8):17221731. doi: 10.1021/acs.chemrestox.9b00230. Epub 2019 Aug PMID: 31328504 
  14. Formulation of antimicrobial tobramycin loaded PLGA nanoparticles via complexation with AOT, Marcus Hill, Richard Cunningham, Rania Hathout, John Hardy, Marie Migaud, J Funct Biomater. 2019 Jun 13;10(2). pii: E26. doi: 10.3390/jfb10020026. PMID: 31200522 
  15. Slc12a8 is a nicotinamide mononucleotide transporter, Grozio A, Mills KF, Yoshino J, Bruzzone S, Sociali G, Tokizane K, Lei HC, Cunningham R, Sasaki Y, Migaud ME, Imai SI. Nat Metab. 2019 Jan;1(1):47-57. doi: 10.1038/s42255-018-0009-4. Epub 2019 Jan 7. 
  16. The chemistry of the Vitamin B3 Metabolome, M. Makarov; S. J. Trammell; M. E. Migaud, Biochemical Society Transactions (2019), 47(1), 131-147. 
  17. Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives, Makarov, Mikhail V.; Migaud, Marie E. Beilstein Journal of Organic Chemistry (2019), 15, 401-430. 
  18. Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring, Ear, Po Hien; Chadda, Ankita; Gumusoglu, Serena B.; Schmidt, Mark S.; Vogeler, Sophia; Malicoat, Johnny; Kadel, Jacob; Moore, Michelle M.; Migaud, Marie E.; Stevens, Hanna E.; Brenner, Charles. Cell Reports (2019), 26(4), 969-983.e4.    
  19. Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation  Minhas, Paras S.; Liu, Ling; Moon, Peter K.; Joshi, Amit U.; Dove, Christopher; Mhatre, Siddhita; Contrepois,  Kevin; Wang, Qian; Lee, Brittany A.; Coronado, Michael; Bernstein, Daniel; Snyder, Michael P.; Migaud, Marie; Majeti, Ravindra; Mochly-Rosen, Daria; Rabinowitz, Joshua D.; Andreasson, Katrin I. Nature Immunology (2019), 20(1), 50-63.  
  20. Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration, Liu, Hui-wen; Smith, Chadwick B.; Schmidt, Mark S.; Cambronne, Xiaolu A.; Cohen, Michael S.; Migaud, Marie E.; Brenner, Charles; Goodman, Richard H. Proceedings of the National Academy of Sciences of the United States of America (2018), 115(42), 10654-10659.   
  21. NAD metabolome analysis in human cells using 1H NMR spectroscopy, Shabalin, Konstantin; Nerinovski, Kirill; Yakimov, Alexander; Kulikova, Veronika; Svetlova, Maria; Solovjeva, Ljudmila; Khodorkovskiy, Mikhail; Gambaryan, Stepan; Cunningham, Richard; Migaud, Marie E.; Ziegler, M; Nikiforov, A.. International Journal of Molecular Sciences (2018), 19(12), 3906/1-3906/14.  
  22. Nicotinamide adenine dinucleotide is transported into mammalian mitochondria, Antonio Davila, Jr., Ling Liu , Karthikeyani Chellappa, Philip Redpath, Eiko Nakamaru Ogiso,  Zhigang Zhang,  Marie E., Joshua D. Rabinowitz, and Joseph A. Baur, eLife, 31-10-2017-ISRA-eLife-33246, 2018.  
  23. Quantitative analysis of NAD synthesis-breakdown fluxes, Ling Liu, Xiaoyang Su, William J. Quinn III, Sheng  Hui1, Kristin Krukenberg, David W. Frederick, Philip Redpath, Le Zhan, Karthikeyani Chellappa, Eileen White, Marie Migaud, Timothy J. Mitchison, Joseph A. Baur, Joshua D. Rabinowitz; Cell Metab. 2018 May 1;27(5):1067-1080.e5. doi: 10.1016/j.cmet.2018.03.018. 
  24. Metabolomic Profiling of Long-Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain. Menni C, Migaud M, Kastenmüller G, Pallister T, Zierer J, Peters A, Mohney RP, Spector TD, Bagnardi V, Gieger C, Moore SC, Valdes AM. Obesity (Silver Spring). 2017 Sep;25(9):1618-1624. doi: 10.1002/oby.21922. Epub 2017 Jul 31. PMID: 28758372 
  25. Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells. Fletcher RS, Ratajczak J, Doig CL, Oakey LA, Callingham R, Da  Silva Xavier G, Garten A, Elhassan YS, Redpath P, Migaud ME, Philp A, Brenner C, Canto C, Lavery GG. Mol Metab. 2017 May 29;6(8):819-832. doi: 10.1016/j.molmet.2017.05.011. eCollection 2017 Aug. PMID: 28752046.
  26. Kathryn F. Mills, Shohei Yoshida, Liana R. Stein, Alessia Grozio, Shunsuke Kubota, Yo Sasaki, Philip Redpath, Marie E. Migaud, Rajendra S. Apte, Rajendra S. Apte, Koji Uchida, Jun Yoshino, Shin ichiro Imai, Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice, 2016, vol. 24, issue 6, p. 795-806. Cell Metabolism  
  27. Richard Cunningham, Nancy C. Forero-Martinez, Christopher Hardacre, Christopher Hardacre, Tristan G A Youngs, Marie E. Migaud, Solubility study of tobramycin in room temperature ionic liquids: an experimental and computational based study. 2016, vol. 6, issue 109, p. 107214-107218. 
  28. Joanna Ratajczak · Magali Joffraud · Samuel A. J. Trammell ·[...] · Marie E. Migaud, [...],  Charles Brenner and C. Carles Cantó, (2016) "NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nature Commun. 10/2016; 7:13103. DOI:10.1038/ncomms13103 
  29. S. Trammell […] P. Redpath, M. Migaud, C. Brenner (2016) Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.  Nature Commun. 10/2016; 7:12948. DOI:10.1038/ncomms12948.  
  30. Frederick DW, Loro E, Liu L, Davila A, Chellappa K, Silverman IM, Quinn WJ, Gosai SJ, Tichy ED, Davis JG, Mourkioti F, Gregory BD, Dellinger RW, Redpath P, Migaud ME, Nakamaru-Ogiso E, Rabinowitz JD, Khurana TS, Baur JA. (2016) Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle. Cell Metab. 2016;24(2):269-82. 
  31. Trammell, S. A. J., Yu, L., Redpath, P., Migaud, M. E., & Brenner, C. (2016). Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. The Journal of Nutrition. 10.3945/jn.116.230078. 
  32. Ashley S. Massey et al., M. E. Migaud, and Helen O. McCarthy. (2016) Potentiating the anti-cancer properties of bisphosphonates by nano-complexation with the cationic amphipathic peptide, RALA. First published 8th March 16, DOI: 10.1021/acs.molpharmaceut.5b00670. 
  33. Cristina Menni et al., Marie Migaud, Ana M. Valdes. (2016) Metabolomic profiling to dissect the role of visceral fat in cardiometabolic health. Obesity, 24(6), 1380–1388.
▼   Current Projects
  • Biosynthesis and catabolism of riboflavin cofactors
  • Catabolites of NAD(P) and their functions
  • Ovarian and Breast Tumor Microenvironment from a micronutrionents’ perspective
  • Novel precursors of redox and signaling cofactors.
▼   Current Activities
  • Director of the Mass Spectrometry Core Facilities
  • Reviewer for the European Commission REA MSCA-EC-ITN programs, including International Fellowship Grant scheme of MSCA-EC-IF
  • L’Oreal-UNESCO Reader (Proposal reviewer) (yearly) External 
  • Program Examiner for International Academic Institutions
  • Member of Editorial Boards: Frontiers, DMPI, Medicina
  • National and International Collaborations: USA, Germany, Russia, United Kingdom, France, Switzerland, Norway
▼   Awards

2018 
Mayer Mitchell Award for Excellence in Cancer Research, USA, Alabama, USA

 

2015 
Helen C. Levitt Endowed Annual Visiting Professorship award- Carver College of Medicine; University of Iowa, Iowa, USA

 

2014
Internationalization Awards, Queen’s University Belfast, UK

 

2013-2015 
Green Impact Awards- Silver and Gold awards, Pharmacy, QUB

 

2014 
UK Scientific Women Academic Network (SWAN) Silver award; Chair, School of Pharmacy. Nationwide and European Action to promote Gender Equality and Diversity in Higher Education, UK

 

2010 
UK Scientific Women Academic Network (SWAN) Silver award; Chair, School of Chemistry and Chemical Engineering, Silver SWAN award; Chair, QUB, UK

 

2008 
UK Scientific Women Academic Network (SWAN) Bronze SWAN award; Chair, School of Chemistry and Chemical Engineering, Silver SWAN award; Chair, QUB, UK

 

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