Professor Heike Heuer is Professor for Molecular Thyroidology at the Department of Endocrinology, Diabetes and Metabolism at University Hospital Essen – University Duisburg-Essen in Germany. She is interested in thyroid hormone actions in the central nervous system (CNS) and uses mouse models to investigate the function of thyroid hormone transporters and to develop treatment strategies for patients with Allan-Herndon-Dudley syndrome. As the 2021 British Thyroid Association Pitt-Rivers Lecturer, she will present a plenary at SfE BES 2021. In our interview, she talks about her research and highlights how preclinical animal studies can lead to important and useful clinical advances.

Tell us about your career so far

I studied biochemistry at the Leibniz University in Hanover, followed by a PhD in neuroendocrinology at the Max-Planck Institute for Experimental Endocrinology. As a postdoctoral fellow I joined Carol Mason’s lab in the Center for Neurobiology and Behavior at Columbia University, New York, where I extended my neurobiology training. I was appointed as an independent, junior group leader at the Leibniz Institute on Aging/Fritz Lipmann Institute in Jena, where I headed a neuroendocrinology group working on thyroid hormone transporters. Later I became a tenured group leader at the Leibniz Research Institute for Environmental Medicine in Düsseldorf and in 2018, I was appointed as a University Professor for Molecular Thyroidology in Essen.

What inspired you into research?

“I’m pleased that our findings contributed to the rapid establishment of a treatment option for patients with a rare and devastating disease.”

I became interested in neuroendocrinology during my undergraduate degree, as I found it fascinating how peripheral organs communicated with the brain and vice versa. Encouraged by my mentors, Karl Bauer and Theo Visser, I started my research career by examining the thyrotropin-releasing hormone (TRH) signaling system in the rodent CNS. I then became intrigued by the profound effects that thyroid hormones exerted on brain development and function. The breakthrough discovery of the highly specific thyroid hormone transporter MCT8 by Theo Visser and colleagues strongly influenced my research. It became unequivocally clear that thyroid hormones need transporters for transmembrane passage and, consequently, for reaching their receptors. The profound neurological phenotype of patients with inactivating MCT8 mutations (also known as Allan-Herndon-Dudley syndrome) encouraged us to develop mouse models in order to understand the underlying pathogenic mechanisms and also to investigate treatment strategies.

Now, a major focus of my group is to analyse cell-specific TH transporter mouse mutants as we aim to understand which proteins act as critical ‘gate-keepers’ for TH in the CNS, as well as in peripheral organs and how their transport activity is affected under pathophysiological conditions.

“Endocrinology is, in my opinion, a very attractive and exciting research field that offers many interdisciplinary interactions and cross-links with other disciplines.”

What are you proudest of in your career, so far?

With the generation of mice lacking both thyroid hormone transporter Mct8 and Oatp1c1, we successfully established a mouse model that replicates many clinical features of patients with Allan-Herndon-Dudley syndrome, a severe form of psychomotor retardation. Using this animal model, we were able to test therapeutic strategies including the application of the thyroid hormone analog, Triac. This treatment improved many neural impairments and based on our preclinical data, a first Triac Trial was successfully conducted, and a second Triac Trial is in progress. This highlights the importance of preclinical animal studies and I’m pleased that our findings contributed to the rapid establishment of a treatment option for patients with a rare and devastating disease.

What do you enjoy most about your work?

I mostly enjoy lively discussions with colleagues, coworkers and students about scientific studies and novel results.

What will you be presenting in your lecture at SfE BES 2021?

It is indeed a great honor for me to present the Pitt-Rivers lecture at the SfE BES 2021 as Rosalind Pitt-Rivers not only discovered T3 in her pioneering work, but was also the first to establish that the thyroid hormone metabolite, Triac, exerts T3-like effects in animals. To acknowledge her seminal achievements, I will highlight not only the impact of thyroid hormone transporter deficiency on brain development but also discuss how Triac application can improve neural differentiation, and may be a promising treatment option for patients with Allan-Herndon-Dudley syndrome.

What do you think are the main challenges in your field right now?

According to the classical view, TH action is largely determined by circulating TH levels that are mainly regulated by negative feedback loops within the hypothalamus-pituitary-thyroid axis. However, with the recent discovery of patients harboring defects in local TH signaling, e.g. due to genetic TH transporter or receptor mutations, this classical concept of TH action has been challenged. These patients clearly display a discordance between serum TH and TSH concentrations on the one hand, and tissue-specific TH deficiency and/or excess on the other hand. In other words, patients with TH and TSH concentrations within the normal range may still have a “hypothyroid” brain despite a “euthyroid” liver and may benefit from a CNS-specific TH supply. A major challenge is now to identify suitable biomarkers that indicate a tissue-specific change in TH status and to develop clinical strategies to modulate TH status in a cell/organ-specific manner. Certainly, a change in perspective from systemic towards local, tissue-oriented TH action will be needed for comprehensive understanding of TH effects in the body and will ultimately pave the way for the development of novel approaches for modulating cell-specific TH signaling under certain pathophysiological conditions.

What do you think will be the next breakthrough in your field?

I envision that the discoveries of novel mechanisms underlying local control of thyroid hormone action (e.g. identification of additional TH specific transporters or novel modes of TH action) will open new avenues to modulate TH signaling in a tissue- or even cell-specific manner (by applying e.g. novel TH receptor agonists, specific TH transporter inhibitors or novel trojan-horse hormone compounds).

Any words of wisdom for aspiring endocrinologists?

Endocrinology is, in my opinion, a very attractive and exciting research field that offers many interdisciplinary interactions and cross-links with other disciplines. Therefore, I can only strongly encourage young researchers or clinicians to become “endocrinologists”.

And for some words of wisdom, ‘Endocrine systems and their regulatory mechanisms and modes of action are complex – thus do not rely on selected serum values only. Always aim for the complete picture or you might miss important (and maybe yet unknown) local effects.’

You can attend Professor Heike Heuer’s Medal Lecture, “Role of thyroid hormone transporters in brain development and function” on Monday 8 November at 14:00 GMT.

Find out more about the scientific programme for SfE BES 2021.