DIGS-BB – Dresden International Graduate School for Biomedicine and Bioengineering / Research / Research Groups / Nikolaos Perakakis

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Nikolaos Perakakis Group

Mechanisms controlling energy homeostasis in health and in metabolic diseases

Our research focuses on the identification and investigation of important regulators of energy balance in humans, by combining both animal and human studies in a clinical translational approach. First, we aim to reveal the pathophysiological role and predictive value of important hormones/biomolecules for the manifestation and progress of common metabolic diseases (i.e. type 2 diabetes mellitus [T2DM], obesity, metabolic-dysfunction associated steatotic liver disease (MASLD, previously known as NAFLD) in humans. Then, we use this information to generate non-invasive diagnostic-prognostic tools for metabolic diseases and to evaluate possible treatments in animal models.

Approach

Human Studies
We perform observational and interventional human clinical studies with subjects in different energy and disease status, ranging from acute complete energy deprivation (i.e. complete fasting) or chronic energy deficit (anorexia nervosa, women developing hypothalamic amenorrhea due to strenuous exercise) up to conditions of modest or severe energy excess (mild obesity, T2DM, MASLD, morbid obesity, severe dyslipidemia). With the use of these studies, we have previously described novel roles for specific biomolecules (e.g. leptin, follistatin, activin, proglucagon-deriving molecules) in body weight regulation, appetite control, glucose homeostasis and metabolic diseases. We have also used this information to develop accurate models for diagnosing Non-alcoholic Steatohepatitis (NASH, now renamed to MASH) based on blood parameters. (see Figure 1)
In vitro and and in vivo animal studies
We perform cell culture experiments and animal studies evaluating:
1. Mechanisms linking the disruption of energy homeostasis with the development of MASLD
2. The hepatic effects and mechanisms of function of several medications in animal mouse models of MASLD (see Figure 2)
3. The impact of metabolic diseases (obesity, diabetes, MASLD) on immune mechanisms and response to infections

Nikolaos Perakakis Research – Figure 1 — Figure 1: We perform clinical studies in order to assess how the levels of certain hormones are regulated in different energy conditions and how strong they are associated with metabolic outcomes. We use this information either alone or combined with data from multiomic procedures in order to develop diagnostic or predictive models of metabolic diseases. Additionally, we evaluate either in interventional human studies or in animal studies, treatments that are related to these hormones and to metabolic diseases.

Nikolaos Perakakis Research – Figure 2 — Figure 2: We have shown that several medications that are currently under clinical evaluation for the treatment of NASH (now renamed MASH) in patients with type 2 diabetes can also improve hepatic status even in the absence of diabetes. These medications demonstrate important differences in the respective mechanisms of action, which supports the notion for their evaluation as combination therapies in the future.

Future Projects and Goals

Identification of novel biomolecules involved in metabolic regulation with the use of omics in different energy and glucose states.
Evaluation of the effect of novel biomolecules and treatments on the development and progression of MASLD.
Assessment of the mechanisms involved in impaired response to infections in metabolic diseases
Investigation of the mechanisms related to sex-based differences in the development and progression of metabolic diseases

Methodological and Technical Expertise

In vivo models of MASLD, obesity and diabetes
Ex vivo (cell culture) models for assessment of immune cell function
Extracellular vesicles extraction and characterization
Human clinical studies: Design, performance, metabolic phenotyping
Biostatistics and omics analysis

CV

since 09/2021
Professor of Metabolic and Vascular Medicine, Director of Clinical Study Center for Metabolic Diseases, Faculty of Medicine, TU Dresden

2016–2021
Post-doctoral fellow (2016–2019) and Instructor of Medicine (2019–2021), Harvard Medical School, Boston, USA

2015
Board Exams for Internal Medicine, Endocrinology and Diabetology, Germany

2013
MD thesis (summa cum laude), Division of Endocrinology and Diabetology, University of Freiburg, Germany

More Information

Perakakis Group at TUD PLID

Selected Publications

Perakakis N et al
Mechanisms and clinical relevance of the bidirectional relationship of viral infections with metabolic diseases
Lancet Diabetes Endocrinol. 11(9):675–93 doi: 10.1016/S2213-8587(23)00154-7 (2023)

Sandforth A, von Schwartzenberg RJ et al
Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS)
Lancet Diabetes Endocrinol. 11(11):798–810 doi: 10.1016/S2213-8587(23)00235-8 (2023)

Nikolaos Perakakis, Konstantinos Stefanakis, Michael Feigh, Sanne S Veidal, Christos S Mantzoros
Elafibranor and liraglutide improve differentially liver health and metabolism in a mouse model of non-alcoholic steatohepatitis
Liver Int. 41(8):1853–66 doi: 10.1111/liv.14888 (2021)

Pavlina Chrysafi*, Nikolaos Perakakis*, Olivia M. Farr, Konstantinos Stefanakis, Natia Peradze, Aleix Sala-Vila & Christos S. Mantzoros
Leptin alters energy intake and fat mass but not energy expenditure in lean subjects
Nature Commun. 11(1):5145 doi: 10.1038/s41467-020-18885-9 (2020) * equal contribution

Nikolaos Perakakis, Stergios A Polyzos, Alireza Yazdani, Aleix Sala-Vila, Jannis Kountouras, Athanasios D Anastasilakis, Christos S Mantzoros
Non-invasive diagnosis of non-alcoholic steatohepatitis and fibrosis with the use of omics and supervised learning: A proof of concept study.
Metabolism 101:154005 doi: 10.1016/j.metabol.2019.154005 (2019)