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February 13, 2017 - Chemist explores vitamin B3’s role in health, disease

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French-born chemist Marie Migaud, Ph.D., is bringing a new and exciting division of research to USA Mitchell Cancer Institute.

An Abraham A. Mitchell Research Scholar, Migaud (pronounced mee-go) joined MCI in November as a professor of oncologic sciences, focused on developing tools to probe the cellular function of B vitamins and their role in disease development and progression.

“I have been working in the field of water-soluble vitamins for almost 20 years,” Migaud said. “We invent new chemicals so biologists can prove how cells use them and how they impact disease and health.”

At MCI, Migaud works with the Molecular and Metabolic Oncology program under the direction of Robert W. Sobol, Ph.D. Her current research focus is the chemistry of the water-soluble vitamin B3, which once converted by the body to nicotinamide adenine dinucleotide, also known as NAD, is used in metabolism and many organs’ functions.

She investigates questions such as:

-- What effect does not having enough vitamin B3 have on a person's health?

-- If we get too much or not enough of the vitamin, how will our cells experience metabolic, genetic or epigenetic (gene activity and expression) change?

-- What are the implications of the use of vitamin B3 for cancer treatment?

Ultimately, Migaud’s research considers how variations in metabolites could affect cancer formation and chemotherapy response.

“As a chemist, Migaud brings a very unique scientific perspective and a valuable research toolset to MCI and to our DNA damage and repair studies in the Molecular and Metabolic Oncology program at MCI,” Sobol said. “I have collaborated on a research project in the past with Marie when she was still a UK-based academic and will continue to do so extensively now and in the future. I am confident that my lab, as well as many other research labs at MCI, with benefit from her unique talents.”

While at Queen’s University Belfast in Northern Ireland, Migaud developed a chemical biology program focusing on vitamin B3 derivatives and newly discovered forms of B3 -- nicotinamide riboside (NR) and  nicotinamide mononucleotide (NMN), precursors of nicotinamide adenine dinucleotide (NAD). There, her studies opened the door to the detailed analysis of NAD metabolism processes and the eventual use of the new forms of vitamin B3 in clinical trials. She developed a robust synthetic program to better collaborate with biological laboratories around the world, which she now brings to MCI.

“Our approach is different in that we not only try and invent new molecules that have biological effects, but we also make quantities that can be shared and lead to more studies and scientific research,” Migaud explained. “We collaborate with other labs around the world; so there is a synergistic perspective.”

She aims to provide her biologist colleagues with the right tools to study B3 while also working with the fine chemical and nutraceutical industry (manufacturers of pharmaceutical-grade supplements) to broaden the impact of her new biologically active molecules.

At MCI, Migaud will supervise a team of six to seven chemists who will work in a new lab starting this summer. “My role is making sure we are on track with what molecules we want to make for our biologists, while devising exciting new chemical methods that minimize the cost and impact on the environment,” she said. “At MCI, we will seek to enhance our ongoing collaboration with industry.”

A native of Paris, Migaud was raised in northwest France near Le Mans. She graduated as a chemical engineer and chemist from Ecole Superieure de Chimie Organique et Minerale, a Paris chemical engineering school, and left France at age 23 to pursue a research career -- first as a graduate student at Purdue University and then at Michigan State University, where she earned her Ph.D. in organic chemistry in 1996.

During high school, she had pursued her favorite subjects: math, science and foreign languages. In college, faced with choosing a major, she did the unexpected. “I literally flipped a coin whether I wanted to become a translator or go into chemical engineering school,” she said.

Now she lives both passions.

“As a scientist, I can travel and use a foreign language as part of my living,” she said. After earning her doctoral degree, Migaud accepted postdoctoral positions in England at Oxford and Bath. She landed her first academic position as a lecturer at Queen’s University in Belfast, where she remained for 16 years.

“I met my husband in Belfast,” she said. “I got a dog so I would get outdoors to walk the dog. Shortly after, my neighbor offered to walk the dog. So, there went that idea; However, I had found my husband.”

Marie and her husband, Archie, have two young sons. The boys immediately adopted Mobile as their new home. “The boys love Mobile,” she said. “I also like it very much.”

Before coming to MCI, Migaud, 48, was awarded the prestigious Helen C. Levitt Endowed Visiting Professorship in the University of Iowa’s Carver College of Medicine, and took a sabbatical year from the UK to come to the US with her family. There, she collaborated with  Charles Brenner, Ph.D., the Roy J. Carver Chair of Biochemistry, where she explored the intricacies of NAD metabolism in mice.

While at Queens University, Migaud’s laboratory synthesized and provided Brenner with his first batch of NR for his animal studies. Because the measurements could be made in animals rather than in cell culture, the outcomes were much more useful to translational sciences and nutritional/medical development in humans, she added. 

As a result, Brenner and his collaborators were able to conduct the first controlled clinical trial of the special form of vitamin B3, finding that NR is safe for humans. The study, announced this past fall, showed that NR increases the levels of NAD, the cell metabolite that is critical for cellular energy production and protection against stress and DNA damage.

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