Introducing Dr. Charles Brenner - Forever curious and passionate for uncharted research questions

Dr. Charles Brenner has been recruited to the University of Helsinki, SWAN (Sustainable Wellbeing Across Lifespan) project, based on profile-building funding from the Research Council of Finland. 

Dr. Brenner has spent decades characterizing enzymes and discovering metabolic pathways to determine how environmental and genetic disturbances in metabolism shape health and disease. He is especially well-known for his groundbreaking research in nicotinamide adenine dinucleotide (NAD), the central catalyst of metabolism. He also brings a current research focus on the rare disease of Citrin Deficiency. 

Already ten years ago, Brenner had his first collaboration with mitochondrial researchers at University of Helsinki led by Academy Professor Anu Suomalainen Wartiovaara when they discovered that people with muscle-presenting mitochondrial disease have low blood NAD.

“In the last year, Anu and I started talking more about common interests. She invited me to be the chief scientific advisor of her startup, NADMED, invited me to be a co-keynote speaker at the inaugural SWAN conference, and then told me about the recruitment opportunity through SWAN. I could not be more pleased to join efforts at the University of Helsinki,” Brenner says.

“I am thrilled to welcome Charles to SWAN. He is an opinion leader in the field of metabolism, personalized medicine and healthy aging that are spearhead areas in our University. He brings in wide expertise in both discovery sciences and commercialization, with collaborative synergies cross different faculties,” Suomalainen Wartiovaara says. 

Ideal research environment

Brenner describes his ideal research environment being one in which he has the time, personnel, opportunities and resources to do very creative work - and University of Helsinki is providing all of that.

“We think that we'll be able to have a very strong, focused staff using excellent shared resources, forming important collaborations with some of the best people in the world in order to answer questions that in some cases people aren't even thinking about yet,” Brenner says.

“Our central goal is to identify questions that haven't occurred to the larger field. We love identifying problems in the literature that can be solved, that people think cannot be solved, or which people are not fully troubled by. To provide a recent example, we got interested in a transcription factor for which at least three or four different compounds had been proposed to be activators, but for which we found the data unconvincing. By proposing an entirely different activator and regulatory mechanism, we were able to reveal the logic of fat synthesis in the liver, a mechanism for hormone regulation that had eluded understanding, and molecular mechanisms of Citrin Deficiency.”

Why work on Citrin Deficiency?

According to Brenner It is difficult to overstate the degree to which rare diseases can help scientists uncover mechanisms that are fundamental to everyone’s health.

“Citrin Deficiency is a disease caused by mutation of a single gene that produces multiple fascinating presentations. The two I found most intriguing are that the patients are lean but accumulate fat in their livers, and that they don’t like sweets. My first conversation with the founders of the Citrin Foundation set me on a journey into what has become central to the focus of my laboratory. In short, we identified how the disease leads to accumulation of a metabolite, how the metabolite turns on a transcription factor, and how that factor leads both to the fatty liver and the dislike of sweets.”

Yet, there are many more open questions. Like many scientists, Brenner draws cartoon-like diagrams that depict proposed biochemical and cellular mechanism of open research questions. When he interviews postdocs, he likes to ask them: “Have we already proven everything? We rarely have.”

“The first figure in our November  is a set of my cartoons. They are a roadmap for people to test the underlying hypotheses, see where they are supported, see where they fail, and then use the resulting knowledge to advance understanding of lipogenesis in health and disease,” Brenner explained. 

Innovation? It's his mother tongue

Brenner’s work has been commercialized multiple times. 

• He spent five formative years in biotech (Chiron Corporation) and a pharma-owned research institute (DNAX) between his Wesleyan undergraduate degree and graduate school at Stanford. He credits this time as a way to appreciate team science and the value of doing discovery research with an eye toward translation.
• As a graduate student, he purified Kex2 protease and developed inhibitors for Furin, which led to the development of small molecule inhibitors of enzymes in the PCSK family in virology and other disease indications.
• At Thomas Jefferson University, he designed fluorigenic enzyme substrates that were developed by Molecular Probes (now in the ThermoFisher catalog).
• At Dartmouth, his discovery of the vitamin activity of nicotinamide riboside created the foundational IP for the NAD-boosting industry. He serves as the chief scientific advisor of Niagen Bioscience, which developed his IP. He advises other companies including Helsinki-based NADMED.
• At University of Iowa, working with Ranjit Bindra at Yale, he discovered that particular cancer genotypes are supersensitive to inhibition of NAD synthesis. They then founded Alphina Therapeutics, which used series A funding to create novel antibody-drug conjugates that are moving toward first-in-human clinical testing.
• Brenner created a new oral medicine technology at City of Hope that he will continue to develop in Helsinki that aims to curb the desire for sweets and alcohol and potentially treat fatty liver disease.

Academic freedom and open science on the agenda

To Brenner academic freedom is of paramount importance. 

“George Orwell wrote presciently about the hazards of orthodoxy and our human duty to acknowledge objective reality against ideological pressure to deny it. I strongly oppose efforts to boycott or silence speakers. Our world is healthier when we engage with ideas and people we are inclined to disagree with. Only through dialog can we achieve understanding,” Brenner says.

Brenner is also a strong advocate for open science and availability of data and full text. He likes to take a critical review of the literature, which he thinks it is important to challenge and correct, particularly in the age of large language models, which are trained on all literature, including literature that is biased and incorrect.

New coursework in sight 

“I really enjoy teaching metabolism to undergraduate and graduate students with a focus on learning how we know what we know and unifying knowledge from different fields. In the past, central carbon metabolism has been taught separately from regulation of gene expression. I would love to develop new coursework at this interface and offer it to University of Helsinki students,” Brenner says.

The profile-building (Profi) funding from the Research Council of Finland funding supports and accelerates the strategic profile-building of Finnish universities to enhance research quality. The latest allocation funds the recruitment of researchers from abroad. See also press release of 2 June: F