黑料天堂

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 黑料天堂 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 鈥渢ask-specific biological investigations鈥�. 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鈥� 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 2: The fate of NAD(P)(H) (Biochemical Society Transactions (2019), 47(1), 131-147.)

Education

 

Postgraduate Training and Research Fellowship Appointments

 

 

 

Faculty Appointments

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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⁺ 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, Cant贸 C. Nicotinamide Riboside and
Dihydronicotinic Acid Riboside Synergistically Increase Intracellular
NAD⁺ by Generating Dihydronicotinamide Riboside. Nutrients. 2022 Jul
1;14(13):2752. doi: 10.3390/nu14132752. PMID: 35807932; PMCID: PMC9269339.

• Biosynthesis and catabolism of riboflavin cofactors
• Catabolites of NAD(P) and their functions
• Ovarian and Breast Tumor Microenvironment from a micronutrionents鈥� perspective
• Novel precursors of redox and signaling cofactors.

• 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鈥橭real-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