Project acronym LUPUSCARE
Project PRECISION CARE IN SYSTEMIC AUTOIMMUNITY: AN INTEGRATED MULTI-TISSUE/LEVEL APPROACH FOR SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Researcher (PI) DIMITRIOS BOUMPAS
Host Institution (HI) IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON
Call Details Advanced Grant (AdG), LS7, ERC-2016-ADG
Summary Systemic lupus erythematosus (SLE) is a heterogeneous disease whereby an interplay of environmental, genetic and epigenetic factors lead to perturbation of complex biological networks culminating into diverse clinical phenotypes of varying severity. High throughput methods have allowed an “initial glimpse” into pathogenesis and have laid the foundations for a molecular-based taxonomy for personalized therapy. Based on our experience with the molecular characterization of SLE, a recently completed RNA sequencing analysis of 150 patients, and our track- record of “paradigm shift” trials in SLE, we will integrate data from multi-tissue analyses with novel technologies to improve its diagnosis, monitoring and therapy, and ask fundamental pathogenetic questions in systemic autoimmunity. More specifically, we will design gene expression panels and “expression profile”/”clinical trait” correlation matrices for diagnostics, personalized immunotherapy and improved clinical trial design. In a systematic multi-tissue approach, we will examine the role of somatic mutations in enhancing immune hyperactivity and the risk for lymphoma. The staggering (7-9:1) female predominance will be elucidated through elaborate genomic, epigenomic and microbiota analyses of family trios. Finally, we will be pursuing the innovative hypothesis that the fundamental abnormalities of SLE lie within the bone marrow hematopoietic stem cells (HSCs) - from which all cells that participate in the pathogenesis of SLE originate - and establish it as a unifying pathogenetic mechanism. By a combination of novel experimental analyses with single cell genomics, multi–omics, humanized animal models, genome editing and an “organ on-a-chip” device, we will validate HSCs as a therapeutic target. The utility of SLE research extends beyond its boundaries, by providing unique insights as to how the immune system recognizes self-constituents and maintains its homeostasis, and how gender impacts on disease biology.
Summary
Systemic lupus erythematosus (SLE) is a heterogeneous disease whereby an interplay of environmental, genetic and epigenetic factors lead to perturbation of complex biological networks culminating into diverse clinical phenotypes of varying severity. High throughput methods have allowed an “initial glimpse” into pathogenesis and have laid the foundations for a molecular-based taxonomy for personalized therapy. Based on our experience with the molecular characterization of SLE, a recently completed RNA sequencing analysis of 150 patients, and our track- record of “paradigm shift” trials in SLE, we will integrate data from multi-tissue analyses with novel technologies to improve its diagnosis, monitoring and therapy, and ask fundamental pathogenetic questions in systemic autoimmunity. More specifically, we will design gene expression panels and “expression profile”/”clinical trait” correlation matrices for diagnostics, personalized immunotherapy and improved clinical trial design. In a systematic multi-tissue approach, we will examine the role of somatic mutations in enhancing immune hyperactivity and the risk for lymphoma. The staggering (7-9:1) female predominance will be elucidated through elaborate genomic, epigenomic and microbiota analyses of family trios. Finally, we will be pursuing the innovative hypothesis that the fundamental abnormalities of SLE lie within the bone marrow hematopoietic stem cells (HSCs) - from which all cells that participate in the pathogenesis of SLE originate - and establish it as a unifying pathogenetic mechanism. By a combination of novel experimental analyses with single cell genomics, multi–omics, humanized animal models, genome editing and an “organ on-a-chip” device, we will validate HSCs as a therapeutic target. The utility of SLE research extends beyond its boundaries, by providing unique insights as to how the immune system recognizes self-constituents and maintains its homeostasis, and how gender impacts on disease biology.
Max ERC Funding
2 355 000 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym NANOTHERAPY
Project A Novel Nano-container drug carrier for targeted treatment of prostate cancer
Researcher (PI) George Kordas
Host Institution (HI) "NATIONAL CENTER FOR SCIENTIFIC RESEARCH ""DEMOKRITOS"""
Call Details Advanced Grant (AdG), LS7, ERC-2008-AdG
Summary The essence of the proposal is the fabrication of multiple nano containers which exhibit double and triple stimuli response and site recognition. Specifically, the containers will be grafted by Leuprolide (LP) for prostate cancer recognition. Multiple containers will be filled by two drugs (e.g. LP and DOX) in different compartments not interacting with each other chemically (cocktail of drugs, e.g. Container1 Leuprolide (LP) and Container2 Doxorubicin (DOX)). The release can be excited by internal or external stimuli response. The internal stimuli response of our nanocontainers will require simultaneous recognition of pH, redox and/or T of the tumour. The external induction will be caused by RF excitation (hyperthermia). The nanocontainers will identify the tumour first by the agonist (LP). After trapping the container at the tumour, they will be activated by the double and triple internal excitation. This way, we achieve extremely local chemotherapy of the diseased site and the healthy organs will be untouched. Our smart nanocontainers will be tuned for prostate cancer, but our system will be evaluated for other cases such as breast cancer and thrombosis. The containers will be modified (phase transition, volume change, degradation, etc.) and deliver the drug only and if only the two sensors give positive response. The containers can be excited by external induction (Radio Frequency (hyperthermia) RF or laser light). This revolutionary strategy is necessary because the externally induced delivery methods have the disadvantage that the radiofrequency fields, the magnetic fields and the laser lights are not local but they extend over large space, larger than the size of the tumour. One cannot focus from outside the laser beam directly to the tumour only may be due to lack of imaging facilities. Our technology will prevent the release of drugs in sites where the local values correspond to the healthy tissue.
Summary
The essence of the proposal is the fabrication of multiple nano containers which exhibit double and triple stimuli response and site recognition. Specifically, the containers will be grafted by Leuprolide (LP) for prostate cancer recognition. Multiple containers will be filled by two drugs (e.g. LP and DOX) in different compartments not interacting with each other chemically (cocktail of drugs, e.g. Container1 Leuprolide (LP) and Container2 Doxorubicin (DOX)). The release can be excited by internal or external stimuli response. The internal stimuli response of our nanocontainers will require simultaneous recognition of pH, redox and/or T of the tumour. The external induction will be caused by RF excitation (hyperthermia). The nanocontainers will identify the tumour first by the agonist (LP). After trapping the container at the tumour, they will be activated by the double and triple internal excitation. This way, we achieve extremely local chemotherapy of the diseased site and the healthy organs will be untouched. Our smart nanocontainers will be tuned for prostate cancer, but our system will be evaluated for other cases such as breast cancer and thrombosis. The containers will be modified (phase transition, volume change, degradation, etc.) and deliver the drug only and if only the two sensors give positive response. The containers can be excited by external induction (Radio Frequency (hyperthermia) RF or laser light). This revolutionary strategy is necessary because the externally induced delivery methods have the disadvantage that the radiofrequency fields, the magnetic fields and the laser lights are not local but they extend over large space, larger than the size of the tumour. One cannot focus from outside the laser beam directly to the tumour only may be due to lack of imaging facilities. Our technology will prevent the release of drugs in sites where the local values correspond to the healthy tissue.
Max ERC Funding
2 000 000 €
Duration
Start date: 2009-02-01, End date: 2014-01-31
Project acronym SMARTGATE
Project "Smart Gates for the ""Green"" Transistor"
Researcher (PI) Athanasios Dimoulas
Host Institution (HI) "NATIONAL CENTER FOR SCIENTIFIC RESEARCH ""DEMOKRITOS"""
Call Details Advanced Grant (AdG), PE7, ERC-2011-ADG_20110209
Summary Ultra-low voltage/power operation is expected to be an important requirement for future nanoelectronics allowing more dense and fast circuits on one hand and enabling the operation of energy efficient intelligent autonomous systems on the other. In present day devices quite a lot of power is consumed during switching since it requires a minimum bias of 60 mV on the gate to overcome a potential barrier and increase the transistor current by a decade, a process which is fundamentally limited by thermal Boltzmann statistics. We propose the development of novel negative capacitance “smart” gates with a positive feedback and internal amplification to overcome the “Boltzmann tyranny” and obtain steeper slope “green” transistors capable of operating at very low voltage. Metallic systems with a low density of states could provide the required dominant negative contributions to the capacitance due to strong carrier correlation effects. Such metallic systems made of 2D Dirac fermions with linear dispersion bands are supported in graphene and on the surface of the newly discovered topological insulators having the very interesting property that they offer a nearly zero density of states at the band crossing near the charge neutral point. We propose here the graphene and Bi2Se3-based topological insulators as the key components of the targeted “smart” gates. We aim at developing complex gate structures facing the challenges of growth of high purity and high crystalline quality graphene and Bi2Se3 thin films in combination with conventional dielectrics and metals on Si semiconductor in an effort to obtain the required properties and ensure their robust functionality at room temperature. Possible negative capacitance effects will be investigated in terms of generic capacitor electrical characterization, while transistor devices with optimum smart gates will be fabricated to prove the principle of steep slope switching.
Summary
Ultra-low voltage/power operation is expected to be an important requirement for future nanoelectronics allowing more dense and fast circuits on one hand and enabling the operation of energy efficient intelligent autonomous systems on the other. In present day devices quite a lot of power is consumed during switching since it requires a minimum bias of 60 mV on the gate to overcome a potential barrier and increase the transistor current by a decade, a process which is fundamentally limited by thermal Boltzmann statistics. We propose the development of novel negative capacitance “smart” gates with a positive feedback and internal amplification to overcome the “Boltzmann tyranny” and obtain steeper slope “green” transistors capable of operating at very low voltage. Metallic systems with a low density of states could provide the required dominant negative contributions to the capacitance due to strong carrier correlation effects. Such metallic systems made of 2D Dirac fermions with linear dispersion bands are supported in graphene and on the surface of the newly discovered topological insulators having the very interesting property that they offer a nearly zero density of states at the band crossing near the charge neutral point. We propose here the graphene and Bi2Se3-based topological insulators as the key components of the targeted “smart” gates. We aim at developing complex gate structures facing the challenges of growth of high purity and high crystalline quality graphene and Bi2Se3 thin films in combination with conventional dielectrics and metals on Si semiconductor in an effort to obtain the required properties and ensure their robust functionality at room temperature. Possible negative capacitance effects will be investigated in terms of generic capacitor electrical characterization, while transistor devices with optimum smart gates will be fabricated to prove the principle of steep slope switching.
Max ERC Funding
1 221 611 €
Duration
Start date: 2012-01-01, End date: 2016-07-31
