How we work
Benefiting from its status as an independent foundation, Seerave is building diverse partnerships and supporting efforts which bring novel benign approaches to cancer patients as quickly as possible. To speed up progress and reduce duplication, Seerave believes that cross-disciplinary and cross-border collaboration from “bench to bedside” is necessary. This may include academic researchers, clinicians, young startups as well as ventures from different fields of life sciences and technology. We act as a catalyst to join the dots between different endeavors.
We are agnostic about the partners we work with and are open to discussions with academic researchers, clinicians, young startups as well as ventures from different fields of life sciences and technology.
The key criteria is that they share our conviction that more benign approaches can be developed to treat cancers and other illnesses by modulating the nutrition / microbiome / metabolite / immune system axis.
We are in discussions with potential partners both in Europe and the US, screening potential projects which would fit our strict selection criteria and merit support by the foundation.
Longitudinal analysis of the nutritional status and microbiome composition in melanoma patients undergoing immunotherapy
Seerave Foundation is supporting two independent centers performing complementary prospective clinical studies:
1) University Medical Center Groningen (UMCG), Netherlands, under the supervision of Prof. Geke Hospers and Prof. Rinse Weersma. A Seerave Fellow at UMCG will coordinate the efforts undertaken.
2) King’s College London (KCL), United Kingdom, under the supervision of Prof. Tim Spector and Dr. Veronique Bataille. KCL will lead a consortium of UK Melanoma Centres
Both studies aim at performing longitudinal analysis of the nutritional status and the composition and function of the gut microbiome in melanoma patients undergoing immunotherapy using metagenomic and metabolomic approaches. The ultimate goal is to integrate the collected data into predictive “–omics signatures” including other biomarkers from blood and tumors, host genetics, immunomics as well as other clinical parameters.
More and more evidence suggests that the gut microbiome regulates host immunity and also modulates the efficacy and side-effects of cancer chemo- and immunotherapy. At the same time, multiple modulators including diet are known to influence the composition and/or the metabolic output of the gut microbiome. However, it is currently unknown whether different nutritional status of cancer patients might influence the composition and/or the metabolic output of the gut microbiome, and if so, whether these parameters could indeed stratify patients responding or not-responding to cancer immunotherapy. Given that nutrition may represent the safest and easiest modulator of the gut microbiome, understanding the relationship between nutrition, the microbiome, and anti-cancer immunity could a) generate hypothesis for mechanistic work in pre-clinical models, and b) open highly interesting therapeutic avenues for cancer patients.
Mechanisms of nutrient-induced immunomodulation in pre-clinical cancer models
Seerave Foundation is supporting pre-clinical research in the labs of Prof. Laurence Zitvogel and Prof. Guido Kroemer at the Institut Gustave Roussy (IGR) Paris, France, aiming at 1) identifying the molecular mechanism of action of how nutrients can affect local and systemic cancer immunity, and 2) establishing biomarkers that will allow one to quantify the effects of nutritional interventions on the microbiome/metabolite/immunity axis. A Seerave Fellow in each lab will coordinate the efforts undertaken.
Even though more and more correlative data from clinics suggests that the gut microbiome regulates the efficacy and side-effects of cancer chemo- and immunotherapy, the exact underlying mechanisms are currently unknown. A better understanding of the molecular pathways involved in the nutrition/microbiome/metabolite/immunity axis will be needed in order to develop rational clinical interventions. Hypothesis-driven research in pre-clinical cancer models may allow one to decipher some of the involved mechanisms. One such hypothesis comes from the field of autophagy, a core process of cell metabolism responsible for the recycling unneeded or damaged intracellular material. Evidence suggests that autophagy is essential for proper immune cell function and stimulating autophagy has been shown to enhance cancer therapies by inducing better anti-tumor immunity. Interestingly, different nutrients including Spermidine, a so-called Caloric Restriction Mimetics (CRMs), have been shown to induce autophagy, thereby altering cellular function.
Fecal microbiome transfer in patients with severe depression
Seerave Foundation is supporting a prospective clinical study at the University Psychiatrics Clinics Basel (UPK), Switzerland, aiming to determine for the first time if fecal microbiota transplantation (FMT) improves the effect of antidepressants in patients with severe Major Depressive Disorder (MDD).
The prevalence of psychiatric disorders such as major depression is increasing rapidly. However, only 50% of patients respond to antidepressants and often then with side effects, while about 20% don’t respond to any treatment. Recent interest has been drawn towards the importance of biochemical signaling between the gastrointestinal tract and the central nervous system also known as the “microbiome-gut-brain axis”, as for example via the vagus nerve. A new underexplored method to alter the gastrointestinal microbiota involves fecal microbiota transplantation (FMT). The goal of the procedure is to introduce or restore a stable microbial community in the gut by transferring intestinal microbiota from a healthy donor to the patient. FMT is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. At the same time, applications in previously unexpected areas including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors have shown health enhancing results.