Projects

Our overall aim is to get novel treatment approaches to cancer patients as quickly as possible by accelerating the creation of solid and reproducible evidence. We support mechanistic, observational and interventional studies across the full spectrum of scientific and clinical research as well as other projects that may act as accelerators to our mission. There are two essential features of our endeavors: 1) each project is complementary within the framework of our nutrition/microbiome/immune system axis, 2) each institution conducting a research project nominates a Seerave “Fellow”. These “Fellows” together with their colleagues are encouraged to collaborate across disciplinary and geographic borders to increase the overall impact of the Seerave Foundation.

Preclinical mechanistic (Evidence generation)
Clinical observational (Evidence generation)
Clinical interventional (Evidence generation)
Other activities (Enabling projects)

Impact of personalised nutrition on breast cancer patients

Prof. Eran Segal

show details

Impact of nutrients on cancer immunotherapy

Prof. Laurence Zitvogel

Prof. Guido Kroemer

show details

Personalised Nutrition Immune Response Algorithm (PNIRA) project: personalised nutrition intervention to boost immune response and efficacy of cancer therapies.

Goals

Seerave Foundation is supporting a randomized clinical trial that assesses the effects of a personalised nutritional intervention in combination to conventional therapy in breast cancer patients.  The trial will be performed as a collaborative effort between the lab of Prof. Eran Segal at Weizmann Institute and Sheba Medical Center. The aims of the trial are 1) to develop predictive algorithms from associations between nutrition, glycemic response, gut microbiota, antibody and T cell responses, 2) with the aid of these algorithms, to validate and/or further develop personalized dietary intervention (and possibly other lifestyle) protocols which will improve clinical outcomes and minimize the use of invasive medicine, and 3) extend these algorithms and other protocols to other cancer types.

Partner institution
Principle investigator
Prof. Eran Segal
Seerave Fellows
Dr. Thomas Vogel
Background

Improving the success of adjuvant treatment of breast cancer and understanding the underlying causes of interpersonal variation in the response to treatment is of utmost importance for breast cancer patients’ prognosis and survival. Multiple factors may contribute to this inter-personal variation, including baseline gut microbiome composition, diet, immune system repertoire, and interactions among all of these factors. It has previously been established that a) diet can shape the microbiome both in terms of composition and function, b) the microbiome contributes to shaping the immune system. It is thus conceivable that optimizing this axis by applying a personalised nutritional regimen based on gut microbiome profiles will boost anti-tumour immune responses and improve the efficacy of therapy in breast cancer patients.

Timeline
Start
01/07/2018
Hide

Mechanisms of nutrient-induced immunomodulation in pre-clinical cancer models

Goals

Seerave Foundation is supporting pre-clinical research in the labs of Prof. Laurence Zitvogel and Prof. Guido Kroemer at the Institut Gustave Roussy (IGR) in 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. Three Seerave Fellows will coordinate the efforts undertaken.

Partner institution
Principle investigators
Prof. Laurence Zitvogel
Prof. Guido Kroemer
Seerave Fellows
Dr. Gladys Ferrere
Dr. Jonathan Pol
Dr. Maryam Tidjani Alou
Background

Even though more and more correlative data from clinics suggests that the gut microbiome regulates the efficacy and side-effects of cancer chemotherapy 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 of 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. Another hypothesis is that the gut microbiome converts nutrients such as fibers and polyphenols to metabolites that then bind to receptors on host immune cells, thereby modulating their function.

Timeline
Start
01/11/2017
Hide

Universitair Medisch Centrum Groningen

Groningen, The Netherlands

Predicting response to immunotherapy based on diet & microbiome

Prof. Geke Hospers

Prof. Rinse Weersma

show details

Predicting response to immunotherapy based on microbiome & metabolites

Prof. Tim Spector

Prof. Veronique Bataille

Dr. Paul Nathan

show details

Longitudinal analysis of the nutritional status and microbiome composition in melanoma patients undergoing immunotherapy

Goals

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. The ultimate goal is to integrate the collected data into predictive “–omics signatures” including other biomarkers from blood and tumors, host genetics and immunomics as well as other clinical parameters.

Principle investigators
Prof. Geke Hospers
Prof. Rinse Weersma
Background

More and more evidence from studies in mice but also humans suggests that the gut microbiome regulates host immunity and also modulates the efficacy and side-effects of cancer chemotherapy and immunotherapy (details in our Science section). 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 hypotheses for mechanistic work in pre-clinical models, and b) open highly interesting therapeutic avenues for cancer patients.

Timeline
Start
01/11/2017
Hide

Predicting Response to Immunotherapy for Melanoma with gut Microbiome and metabolomics (PRIMM study)

Goals

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. The ultimate goal is to integrate the collected data into predictive “–omics signatures” including other biomarkers from blood and tumors, host genetics and immunomics as well as other clinical parameters.

 

Partner institution
Principle investigators
Prof. Tim Spector
Dr. Veronique Bataille
Dr. Paul Nathan
Seerave Fellows
Dr. Karla Lee
Dr. Amrita Vijay
Background

More and more evidence from studies in mice but also humans suggests that the gut microbiome regulates host immunity and also modulates the efficacy and side-effects of cancer chemotherapy and immunotherapy (details in our Science section). 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 hypotheses for mechanistic work in pre-clinical models, and b) open highly interesting therapeutic avenues for cancer patients.

Timeline
Start
01/11/2017
Hide

Impact of microbiome-derived metabolites on immune cells

Prof. Naama Geva-Zatorsky

show details

Fecal microbiome transfer in patients with severe depression

Dr. Laura Mählmann

Dr. André Schmidt

show details

Characterizing Microbiome-Derived Metabolites That Directly impact The Immune System (CMMIIS Study)

Goals

Seerave Foundation is supporting pre-clinical research in the labs of Prof. Naama Geva-Zatorsky, aiming at identifying metabolites produced by the gut microbiota that directly impact the immune system and generate in depth mechanistic understanding about their receptors and downstream signaling. Identifying such metabolites will represent the first step in generating an in-depth mechanistic understanding of the downstream molecular pathways responsible for delivering signals from the bacterial cell to the host immune cell. This should guide the development of novel therapeutic interventions to strengthen immune responses in cancer patients including personalized and rationally designed nutrient compositions.

Principle investigator
Prof. Naama Geva-Zatorsky
Seerave Fellows
Dr. Tal-avi Gefen
Noa Mandelbaum
Background

The gut microbiome has co-evolved with the human host for millennia, creating an inextricable and dependent relationship, where the gut bacteria became a vital component of the human immune system. Both soluble metabolites secreted by the bacteria as well as cellular components such as lipopolysaccharides (LPS) found in the membrane of certain bacteria have been shown to influence the immune system. Naama Geva-Zatorsky recently identified more than 50 different bacterial strains from the gut microbiome that individually impact different systemic immune responses in mice. However, it is still unknown which metabolites secreted by these bacterial strains are the ones responsible for the modulation of immune responses, and whether the production of these metabolites depends on the availability of specific nutrients. Understanding these relationships may lead to the identification of novel, rationally-designed nutritional approaches to aid anti-cancer therapy.

Timeline
Start
01/07/2018
Hide

Fecal microbiome transfer in patients with severe depression

Goals

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).

Project leaders
Dr. André Schmidt
Dr. Laura Mählmann (former)
Background

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 of FMT have shown health enhancing results in previously unexpected areas including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and oncology.

Timeline
Start
01/03/2017
Hide

Yerosha Productions

New York City, USA

Documentary movie: "Missing Microbes"

Sarah Schenk

Steven Lawrence

show details

Documentary movie: "Missing Microbes"

Goals

The documentary “Missing Microbes” aims at explaining to a layman audience the state-of-the-art microbiome research and its potential to improve human health. Seerave is supporting this documentary since it will be produced in a rigorous and scientifically sound manner. Furthermore, Seerave is helping the team to navigate the science around the diet/microbiome/immunity/cancer axis.

Director and Producer
Sarah Schenk
Steven Lawrence
Background

Missing Microbes is a feature documentary about the critical role of microbes in human health – and how disrupting our microbes has helped trigger an unprecedented surge in chronic diseases like obesity, diabetes, cancer, allergies, and autism. As the film follows globe-trotting microbiologists Martin Blaser and Gloria Dominguez-Bello on their mission to end this crisis before it’s too late, it also tells the stories of patients in China, Israel, Europe, and the USA as they search for cures to these modern plagues.

 

Timeline
Start
01/07/2018
Hide

Impact of personalised nutrition on breast cancer patients

Prof. Eran Segal

show details

Personalised Nutrition Immune Response Algorithm (PNIRA) project: personalised nutrition intervention to boost immune response and efficacy of cancer therapies.

Goals

Seerave Foundation is supporting a randomized clinical trial that assesses the effects of a personalised nutritional intervention in combination to conventional therapy in breast cancer patients.  The trial will be performed as a collaborative effort between the lab of Prof. Eran Segal at Weizmann Institute and Sheba Medical Center. The aims of the trial are 1) to develop predictive algorithms from associations between nutrition, glycemic response, gut microbiota, antibody and T cell responses, 2) with the aid of these algorithms, to validate and/or further develop personalized dietary intervention (and possibly other lifestyle) protocols which will improve clinical outcomes and minimize the use of invasive medicine, and 3) extend these algorithms and other protocols to other cancer types.

Partner institution
Principle investigator
Prof. Eran Segal
Seerave Fellows
Dr. Thomas Vogel
Background

Improving the success of adjuvant treatment of breast cancer and understanding the underlying causes of interpersonal variation in the response to treatment is of utmost importance for breast cancer patients’ prognosis and survival. Multiple factors may contribute to this inter-personal variation, including baseline gut microbiome composition, diet, immune system repertoire, and interactions among all of these factors. It has previously been established that a) diet can shape the microbiome both in terms of composition and function, b) the microbiome contributes to shaping the immune system. It is thus conceivable that optimizing this axis by applying a personalised nutritional regimen based on gut microbiome profiles will boost anti-tumour immune responses and improve the efficacy of therapy in breast cancer patients.

Timeline
Start
01/07/2018
Hide

Impact of nutrients on cancer immunotherapy

Prof. Laurence Zitvogel

Prof. Guido Kroemer

show details

Mechanisms of nutrient-induced immunomodulation in pre-clinical cancer models

Goals

Seerave Foundation is supporting pre-clinical research in the labs of Prof. Laurence Zitvogel and Prof. Guido Kroemer at the Institut Gustave Roussy (IGR) in 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. Three Seerave Fellows will coordinate the efforts undertaken.

Partner institution
Principle investigators
Prof. Laurence Zitvogel
Prof. Guido Kroemer
Seerave Fellows
Dr. Gladys Ferrere
Dr. Jonathan Pol
Dr. Maryam Tidjani Alou
Background

Even though more and more correlative data from clinics suggests that the gut microbiome regulates the efficacy and side-effects of cancer chemotherapy 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 of 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. Another hypothesis is that the gut microbiome converts nutrients such as fibers and polyphenols to metabolites that then bind to receptors on host immune cells, thereby modulating their function.

Timeline
Start
01/11/2017
Hide

Universitair Medisch Centrum Groningen

Groningen, The Netherlands

Predicting response to immunotherapy based on diet & microbiome

Prof. Geke Hospers

Prof. Rinse Weersma

show details

Longitudinal analysis of the nutritional status and microbiome composition in melanoma patients undergoing immunotherapy

Goals

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. The ultimate goal is to integrate the collected data into predictive “–omics signatures” including other biomarkers from blood and tumors, host genetics and immunomics as well as other clinical parameters.

Principle investigators
Prof. Geke Hospers
Prof. Rinse Weersma
Background

More and more evidence from studies in mice but also humans suggests that the gut microbiome regulates host immunity and also modulates the efficacy and side-effects of cancer chemotherapy and immunotherapy (details in our Science section). 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 hypotheses for mechanistic work in pre-clinical models, and b) open highly interesting therapeutic avenues for cancer patients.

Timeline
Start
01/11/2017
Hide

Predicting response to immunotherapy based on microbiome & metabolites

Prof. Tim Spector

Prof. Veronique Bataille

Dr. Paul Nathan

show details

Predicting Response to Immunotherapy for Melanoma with gut Microbiome and metabolomics (PRIMM study)

Goals

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. The ultimate goal is to integrate the collected data into predictive “–omics signatures” including other biomarkers from blood and tumors, host genetics and immunomics as well as other clinical parameters.

 

Partner institution
Principle investigators
Prof. Tim Spector
Dr. Veronique Bataille
Dr. Paul Nathan
Seerave Fellows
Dr. Karla Lee
Dr. Amrita Vijay
Background

More and more evidence from studies in mice but also humans suggests that the gut microbiome regulates host immunity and also modulates the efficacy and side-effects of cancer chemotherapy and immunotherapy (details in our Science section). 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 hypotheses for mechanistic work in pre-clinical models, and b) open highly interesting therapeutic avenues for cancer patients.

Timeline
Start
01/11/2017
Hide

Impact of microbiome-derived metabolites on immune cells

Prof. Naama Geva-Zatorsky

show details

Characterizing Microbiome-Derived Metabolites That Directly impact The Immune System (CMMIIS Study)

Goals

Seerave Foundation is supporting pre-clinical research in the labs of Prof. Naama Geva-Zatorsky, aiming at identifying metabolites produced by the gut microbiota that directly impact the immune system and generate in depth mechanistic understanding about their receptors and downstream signaling. Identifying such metabolites will represent the first step in generating an in-depth mechanistic understanding of the downstream molecular pathways responsible for delivering signals from the bacterial cell to the host immune cell. This should guide the development of novel therapeutic interventions to strengthen immune responses in cancer patients including personalized and rationally designed nutrient compositions.

Principle investigator
Prof. Naama Geva-Zatorsky
Seerave Fellows
Dr. Tal-avi Gefen
Noa Mandelbaum
Background

The gut microbiome has co-evolved with the human host for millennia, creating an inextricable and dependent relationship, where the gut bacteria became a vital component of the human immune system. Both soluble metabolites secreted by the bacteria as well as cellular components such as lipopolysaccharides (LPS) found in the membrane of certain bacteria have been shown to influence the immune system. Naama Geva-Zatorsky recently identified more than 50 different bacterial strains from the gut microbiome that individually impact different systemic immune responses in mice. However, it is still unknown which metabolites secreted by these bacterial strains are the ones responsible for the modulation of immune responses, and whether the production of these metabolites depends on the availability of specific nutrients. Understanding these relationships may lead to the identification of novel, rationally-designed nutritional approaches to aid anti-cancer therapy.

Timeline
Start
01/07/2018
Hide

Fecal microbiome transfer in patients with severe depression

Dr. Laura Mählmann

Dr. André Schmidt

show details

Fecal microbiome transfer in patients with severe depression

Goals

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).

Project leaders
Dr. André Schmidt
Dr. Laura Mählmann (former)
Background

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 of FMT have shown health enhancing results in previously unexpected areas including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and oncology.

Timeline
Start
01/03/2017
Hide

Yerosha Productions

New York City, USA

Documentary movie: "Missing Microbes"

Sarah Schenk

Steven Lawrence

show details

Documentary movie: "Missing Microbes"

Goals

The documentary “Missing Microbes” aims at explaining to a layman audience the state-of-the-art microbiome research and its potential to improve human health. Seerave is supporting this documentary since it will be produced in a rigorous and scientifically sound manner. Furthermore, Seerave is helping the team to navigate the science around the diet/microbiome/immunity/cancer axis.

Director and Producer
Sarah Schenk
Steven Lawrence
Background

Missing Microbes is a feature documentary about the critical role of microbes in human health – and how disrupting our microbes has helped trigger an unprecedented surge in chronic diseases like obesity, diabetes, cancer, allergies, and autism. As the film follows globe-trotting microbiologists Martin Blaser and Gloria Dominguez-Bello on their mission to end this crisis before it’s too late, it also tells the stories of patients in China, Israel, Europe, and the USA as they search for cures to these modern plagues.

 

Timeline
Start
01/07/2018
Hide