Brenner has made multiple contributions to molecular biology and biochemistry, beginning with purification and characterization of the Kex2 proprotein convertase at Stanford. He has been funded by agencies including the Leukemia & Lymphoma Society, the March of Dimes, the Burroughs Wellcome Fund, the Beckman Foundation, the Lung Cancer Research Foundation, the National Institutes of Health, and the National Science Foundation. Significant research projects include molecular dissection of the function of the FHITtumor suppressor gene, characterization and inhibition of DNA methylation, and discovery of new steps in nicotinamide adenine dinucleotide metabolism. Notably, the Brenner laboratory discovered that yeast and humans use nicotinamide riboside to make NAD+, for which Brenner was recognized with a William E.M. Lands lectureship at University of Michigan. Dr. Brenner developed targeted, quantitative analysis of the NAD+ metabolome and made fundamental contributions to NAD metabolism including discovery of nicotinic acid riboside-dependent NAD synthesis, elucidating the mechanism of synthesis of nicotinic acid adenine dinucleotide phosphate, and discovering multiple conditions in which NAD metabolism is dysregulated in disease. Brenner is also active in translating NR technologies to treat and prevent human conditions including diabetic and chemotherapeutic peripheral neuropathy, heart failure, and central brain injury. This work includes the first human trial of NR, which demonstrated safe oral availability as an NAD+ precursor. Though Brenner was the first to show that NR increases SIR2 activity and can extend yeast lifespan, his work has not emphasized sirtuins or nonspecific anti-aging claims and instead emphasizes how NR repairs metabolic stresses that dysregulate NAD+ and NADPH. He recently showed that rodent postpartum mothers are under severe metabolic stress to their NAD system and that supplementing such mothers with NR increases maternal weight loss, advances juvenile development and provides long lasting neurodevelopmental advantages into adulthood. Brenner is author of more than 140 publications and was the senior editor of the 2004 book, Oncogenomics: Molecular Approaches to Cancer.
Educational contributions
In 2012, Brenner was asked by the President of the American Society for Biochemistry and Molecular Biology to develop pre-medical curriculum recommendations that would be consistent with a revised MCAT examination. These recommendations, which include development of inorganic, organic and biochemistry coursework that is more geared toward the chemistry of bioorganic functional groups, have been further refined in academic journals. Brenner's work in this area was recognized by the 2016 ASBMB Award for Exemplary Contributions to Education.
Industrial collaborations
Brenner is a former member of the Scientific Advisory Board of Sirtris Pharmaceuticals. He is the founder of NRomics and was a co-founder of ProHeathspan prior to its acquisition by ChromaDex, for which he serves as member of the scientific advisory board and chief scientific advisor.