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@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

Hayat F, Deason JT, Bryan RL, Terkeltaub R, Song W, Kraus WL, Pluth J,
Gassman NR, Migaud ME. Synthesis, Detection, and Metabolism of Pyridone
Ribosides, Products of NAD Overoxidation. Chem Res Toxicol. 2024 Jan 10. doi:
10.1021/acs.chemrestox.3c00264. Epub ahead of print. PMID: 38198686.

Dhuguru J, Dellinger RW, Migaud ME. Defining NAD(P)(H) Catabolism. Nutrients.
2023 Jul 7;15(13):3064. doi: 10.3390/nu15133064. PMID: 37447389; PMCID:
PMC10346783.

Bhasin S, Seals D, Migaud M, Musi N, Baur JA. Nicotinamide Adenine
Dinucleotide in Aging Biology: Potential Applications and Many Unknowns. Endocr
Rev. 2023 Nov 9;44(6):1047-1073. doi: 10.1210/endrev/bnad019. PMID: 37364580.

Balducci E, Braidy N, Migaud M. Editorial: NAD+ metabolism as a novel target
against infection-Volume II. Front Mol Biosci. 2022 Nov 21;9:1087897. doi:
10.3389/fmolb.2022.1087897. PMID: 36479384; PMCID: PMC9720386.

Chellappa K, McReynolds MR, Lu W, Zeng X, Makarov M, Hayat F, Mukherjee S,
Bhat YR, Lingala SR, Shima RT, Descamps HC, Cox T, Ji L, Jankowski C, Chu Q,
Davidson SM, Thaiss CA, Migaud ME, Rabinowitz JD, Baur JA. NAD precursors cycle
between host tissues and the gut microbiome. Cell Metab. 2022 Dec
6;34(12):1947-1959.e5. doi: 10.1016/j.cmet.2022.11.004. PMID: 36476934; PMCID:
PMC9825113.

Hernandez A, Sonavane M, Smith KR, Seiger J, Migaud ME, Gassman NR.
Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial
stress in liver cells. PLoS One. 2022 Dec 6;17(12):e0278516. doi:
10.1371/journal.pone.0278516. PMID: 36472985; PMCID: PMC9725129.

Kropotov A, Kulikova V, Solovjeva L, Yakimov A, Nerinovski K, Svetlova M,
Sudnitsyna J, Plusnina A, Antipova M, Khodorkovskiy M, Migaud ME, Gambaryan S,
Ziegler M, Nikiforov A. Purine nucleoside phosphorylase controls nicotinamide
riboside metabolism in mammalian cells. J Biol Chem. 2022 Dec;298(12):102615.
doi: 10.1016/j.jbc.2022.102615. Epub 2022 Oct 18. PMID: 36265580; PMCID:
PMC9667316.

Buckley DP, Migaud ME, Tanner JJ. Conformational Preferences of Pyridone
Adenine Dinucleotides from Molecular Dynamics Simulations. Int J Mol Sci. 2022
Oct 6;23(19):11866. doi: 10.3390/ijms231911866. PMID: 36233167; PMCID:
PMC9570408.

Li J, Koczor CA, Saville KM, Hayat F, Beiser A, McClellan S, Migaud ME, Sobol
RW. Overcoming Temozolomide Resistance in Glioblastoma via Enhanced
NAD<sup>+</sup> Bioavailability and Inhibition of Poly-ADP-Ribose
Glycohydrolase. Cancers (Basel). 2022 Jul 22;14(15):3572. doi:
10.3390/cancers14153572. PMID: 35892832; PMCID: PMC9331395.

Ciarlo E, Joffraud M, Hayat F, Giner MP, Giroud-Gerbetant J, Sanchez-Garcia
JL, Rumpler M, Moco S, Migaud ME, Cantó C. Nicotinamide Riboside and
Dihydronicotinic Acid Riboside Synergistically Increase Intracellular
NAD<sup>+</sup> by Generating Dihydronicotinamide Riboside. Nutrients. 2022 Jul
1;14(13):2752. doi: 10.3390/nu14132752. PMID: 35807932; PMCID: PMC9269339.

▼   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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