My name is Alejandra Reyes Ruiz and I am of Mexican nationality. I started my scientific carrier in the city of San Nicolás de los Garza (Mexico) where I studied Biotechnology and Genomics at the Universidad Autonoma de Nuevo Leon (UANL).
A long time ago, Heraclitus rightly stated that “no man ever steps in the same river twice, for it's not the same river and he's not the same man”. We undergo continues changes, some of our cells will divide or will die every day. Such control of life and death is vital and the disruption of this regulation can lead to the development of pathologies including cancer. With that in mind, during my bachelor’s degree I participated in a 3-year research project focused in the analysis of the cell death mechanism induced by an immunotherapy in cervical cancer cells at Prof. Ana Carolina Martínez-Torres laboratory. This research determined my particular interest for Biomedical research and allowed me to experience the excitement of science.
Afterwards, I wanted to drive further into the immunology field, and I started a master’s degree in Immunology at the UANL. We must say Memento mori - “remember you must die” - to cancer cells, but it is also important to evaluate the better way for a cancer cell to die. I carried out my master thesis at the Laboratory of Immunology and Virology (Mexico) under the direction of Prof. Ana Carolina Martínez-Torres. We proved that a particular immunotherapy induced immunogenic cell death in breast cancer. This is important because if an agent kills cancer cells in a way that renders them immunogenic, it has a therapeutic benefit. I think that it is delightful how the immune system discriminates between several signals and determines the immunological consequences after cell death. I’ve come to the conclusion that immune tolerance is a fascinating phenomenon. In fact, unlike cancer, there are other pathologies in which immune tolerance is seen as a friend and not as an enemy, phenomenon that completely caught my attention.
For instance, in haemophilia A, the absence of factor VIII (FVIII) as self-antigen can lead to the development of a FVIII-specific immune response after replacement therapy in a substantial number of patients hampering further treatment. As a consequence, there is an urgent need to develop pioneering strategies to induce immune tolerance to FVIII in haemophilia A patients. Hence, during my PhD at Sorbonne University, I will develop novel FVIII-Fc mutant molecules to confer complete materno-foetal tolerance to FVIII. We expect that the injection of FVIII-Fc mutants to pregnant mice will lead to the transplacental delivery of FVIII, the induction of FVIII-specific Tregs in the offspring and complete long-lasting tolerance to exogenous therapeutic FVIII. This project, directed by Prof. Sebastien Lacroix-Desmazes at the Institut national de la santé et de la recherche médicale in Paris (France), will pave the way towards the design of novel strategies for immuno-intervention as early as during foetal life. We believe that the materno-foetal delivery of FVIII-Fc molecules to haemophilia A patients will generate complete tolerance to FVIII.
Starting date: 15th October 2020
My name is Mariarosaria Miranda and I am from Naples, Italy. I got a BSc degree in Health Biotechnology and a MSc degree in Medical biotechnology at the University of Naples, Federico II.
After high school, I chose to devote my studied to the medical research, as the main tool to understand how human body works, find out answers to all the unsolved questions and build the future of therapeutic approaches.
During my bachelor’s degree I had an internship in General Pathology in Prof. Gerolama Condorelli’s lab, where I investigated the role of specific microRNAs in glioblastoma and breast cancer. Furthermore, I won a fellowship in “Advances in drug discovery” in Prague, that gave me the chance to learn more about medical chemistry, drug design and preclinical/clinical development.
Anyway, little by little I became more curious about immunology. For this reason, I had an internship in Prof. Giuseppe Matarese’s lab, where I focused on the study of autoimmune diseases. Indeed, I studied Regulatory T cells and their altered characteristics during autoimmunity (i.e. type I diabetes and multiple sclerosis). In addition, I won a biennial “excellence fellowship” at the University of Naples, Federico II, which gave me the possibility to improve my knowledge in the immunology field.
During my PhD I will focus on the development of novel universal tools for the immuno-monitoring of T-cell responses in patients affected by Haemophilia A. In detail, Major histocompatibility complex class II (MHCII)-restricted peptide presentation is crucial for the selection and subsequent proliferation of antigen specific CD4+ T cells. As yet the repertoire of FVIII peptides presented on HLA-DP has not yet been defined. The goal of this project is to explore the contribution of HLA-DP to FVIII peptide presentation using unique MHC class II dextramer technology.
Starting date: 1st October 2020
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My name is Sarah Scatigna and I’m 23 years old. I am native of Naples, Italy, where I got my Bachelor’s and Master’s Degree in Medical Biotechnologies.
Over the years, I have maintained a strong motivation in life science and in molecular medicine and my passion led me to perform medical research with a great enthusiasm during the internship experiences. In particular, during the Bachelor’s Degree Internship in the laboratory of Professor De Vita, I focused my researches on quantitative and qualitative analysis of a new long-non-coding RNA expression in mouse model.
Then, being very fascinated by Cancer Immunotherapy, I started the MSc Internship at CEINGE, in the laboratory of Professor Zambrano. There I have developed and characterized cargo-expressing oncolytic viruses (based on HSV-1) retargeted to tumour-specific receptors, used as in situ tumour vaccines.
Now I am a PhD student at the Goethe University in Frankfurt, Germany. My PhD project will focus on inducing tolerance towards Factor VIII in Haemophilia A patients. In particular, the main goal will be to prevent and/or reverse the formation of inhibitory anti-FVIII antibodies using third generation chimeric antigen receptor (CAR) regulatory T cells able to suppress FVIII-specific humoral and cellular responses in vitro and in vivo. I am very enthusiastic about this project as CAR therapy is a notable achievement of the last decade in both oncology and haematology fields.
Being part of the EDUC8 consortium will be a great opportunity to study in an international context and to interact with leading scientists from different professional and cultural backgrounds.
I look forward to enriching my scientific and personal experience.
Starting date: 1st October 2020
My name is Payal Suresh Chawla. I obtained my Bachelors degree in Pharmacy from University of Mumbai, India and a Masters degree in Biotechnology at California State University, Fresno.
Under the supervision of distinguished Chair /Professor Dr. Joy Goto , My research aimed to determine the interaction of non protein amino acid β-methyl-amino-l-alanine with amyloid precursor protein in Alzheimers disease. During the masters years, the target of my research has been very broad which has helped me gain knowledge and clarity of neurodegeneration together with the application of in vitro studies and analytical instruments to the field of neuro-biochemistry.
In order to gain hands-on experience with instrumentation , I worked as a Forensic Toxicologist at Central Valley Toxicology,CA where I studied the mechanism of action, toxicity and stability of various drugs of abuse. My experience in a neurobiochemistry laboratory helped me gain a perspective on the mechanisms of drugs and understand the toxic effects in the system. I was able to learn separation techniques such as LC-MS , GC-MS, Triple quad LC-MS to name a few.
My experience with instrumentation and protein separation/small molecule separation gave me an opportunity to work at a leading biotechnology company, AMGEN,South San Francisco as an Associate Scientist. I worked in the Pharmacokinetic and drug metabolism group (Large molecule) where I learnt new proteomics and separation chromatography techniques such as CE-MS and Immunoaffinity purification of novel therapeutic drugs in the pre-clinical phase for inflammation and tumor inhibition.
At UKB, I am working on the general objective to decipher whether Hemophilia-A causing non-sense mutations in different domains of the FVIII molecule allow the translation into truncated FVIII variants with altered intracellular trafficking and different association to MHC-I and MHC-II molecules compared to FVIII wild type. Using Proteomics, stem cell technologies and common molecular techniques we will try to establish a link between FVIII presentation to T-cells and induction of T-cell mediated tolerance/occurrence of allo-immunisation to therapeutic FVIII.
Starting date: 1st October 2020
My name is Eleonora Nardini and I am from Italy. Since high school, I have been fascinated by life at the molecular level, how inanimate molecules coordinate and originate living organisms. Following my curiosity, I decided to study Biotechnology at the University of Bologna and during my BSc thesis at Oxford Brooks University (UK) I had the opportunity to embrace the lab life while investigating the genetics of speech. This internship helped me understand that what I was studying in the lab could be translated outside of it, where it would have an impact to eventually help people. I now acknowledge that this is my true driving force, i.e. to be in the lab searching for the answers that someone in the outside world is waiting for to living a better life.
Therefore, after graduation, I enrolled in a MSc program in Pharmaceutical Biotechnology, to further dive into the applied side of biology. I carried out my master thesis in biochemistry, in the laboratory of Prof. David Sabatini at the Whitehead Institute in Cambridge (USA) where I studied the role of autophagy in RNA metabolism. By using lysosomal RNase (RNASET2) knock out cell lines we demonstrated that the inhibition of mTORC1 pathway caused the accumulation of specific RNA fragments inside the lysosomes. Furthermore, we developed a screening tool for lysosomal RNAs based on TLR8 recognition of ssRNA fragments. It has been this project in particular which aroused my enthusiasm to study the roles of the immune system.
Indeed, the regulation and attenuation of the immune response is as crucial for keeping the human organism safe as the triggering of it, as autoimmune diseases and transplant rejection demonstrate. Similarly, immune tolerance is of vital importance in haemophilia A. These patients - who carry a genetic deficiency in procoagulant protein factor VIII (FVIII) – develop anti - FVIII antibodies which efficiently neutralize the function of the therapeutic protein in the coagulation pathway. Consequently, FVIII immunogenicity is a major concern for the development of successful therapies for this disease. Thus, during my PhD at VU University in the laboratory of Prof. Yvette van Kooyk I will explore glycosylation as a strategy for inducing tolerance to therapeutic FVIII. To further go into details, evidence showed that antigens modified with α2,3-sialic acid target dendritic cells (DCs) via specific binding to inhibitory sialic acid-binding Ig-type lectin receptors (Perdicchio et al. 2016, PNAS). Internalization of Sia – Ag by DCs endows them with the ability to direct the immune response towards an antigen – specific tolerogenic programme by promoting naïve CD4+ T cell differentiation to regulatory T cells and dampening the function of established effector T cells. We therefore hypothesize that conjugation of FVIII with α2,3-sialic acid will induce preventive or therapeutic antigen-specific tolerance.
I am thrilled of being part of the EDUC8 consortium: the partnership with the world of industries, the applicative aspect while starting from fundamental research, the opportunity to work in an international environment are all valuable aspects of the network that will greatly benefit our projects.
Starting date: 1st March 2021
My name is Michela Leoni and I am from Massa Lombarda, Italy. I obtained my bachelor’s degree in biotechnology and my master’s degree in Pharmaceutical Biotechnology at the University of Bologna.
As part of my bachelor’s degree, I did an internship in Prof. Barbara Monti’s laboratory where my work focused on a preliminary study of the transcriptional and epigenetic profile of the neuronal model of AGC1-deficiency. Here, under the attentive supervision of my tutor, I learned how to work in a laboratory environment and in particular with mammalian cell cultures.
During my master thesis project, in the laboratory of Pharmacogenetics and Pharmacogenomics, I studied the changes in the transcriptome that occur with tumorigenic progression of Gastrointestinal Stromal Tumor using RNA-Sequencing. I also started to explore the effects of silencing three genes, identified as differentially expressed in the three samples groups during the RNA-Seq analysis, in GIST cellular model with the final goal of identify new potential druggable targets, a still unmet clinical need.
My PhD project will explore original strategies to induce FVIII-specific tolerance. I will focus on Liver Sinusoidal Endothelial Cells (LSEC), scavenger cells that process and present antigens on MHC class I or MHC class II molecules and have the capacity of regulating CD4+ and CD8+ T cell responses and inducing the development of Treg. Specifically, I will exploit recent advances on the characterization of FVIII-derived immuno-dominant T cell epitopes to induce specific tolerance upon targeting of Liver LSECs with peptide coupled nanoparticles.
Starting date: 1st July 2021
My name is Valeria Porcheddu and I’m Italian. I started my scientific carrier in the University of Sassari, Sardinia, where I studied Biological Sciences. During my internship in the University Hospital of Sassari at the Microbiology and Virology department, I had the opportunity to study the onset of Latent Autoimmune Diabetes, “LADA”. Thus, developing particular interest in the understanding of autoimmune diseases and overall the immune system mechanisms in a broader sense. Willing to enrich my knowledges toward this field, I moved to Ireland where I started my Master Science degree in Immunology at the Trinity College of Dublin. Here, during my internship at the Moyne Institute, I had the opportunity to investigate the molecular mechanisms of passive immunisation through human breast milk against influenza virus and beyond the mere transfer of anti-viral antibody.
My PhD project at “Service d'Ingénierie Moléculaire pour la Santé” (SIMoS) - CEA Paris-Saclay with prof. Bernard Maillere, will be focused on understanding the peptide specificity of FVIII-specific T cells lines.
T cell epitopes might vary from one donor to another owing to HLA polymorphism but also to the severity of the disease. FVIII is a complete foreign molecule for severe Hemophilia A patients, while it is a fully self-molecule for healthy donors. It has been recently revealed that a large T cell repertoire specific for FVIII exists in healthy donors demonstrating that many FVIII-specific T cells escape from central tolerance (Meunier et al, Blood Adv., 2017). The question arises to decipher and compare the fine specificity of the T cell response to FVIIII in healthy donors and Hemophilia A patients in the perspective to anticipate onset of FVIII inhibitors.
The aim of the project will be: the characterisation of the most common shared pool of FVIII specific peptide naturally presented by HLA-DR haplotype; secondly, the determination of specificity, diversity and clonal frequency of FVIII-specific T cells in healthy individuals and in patient with Hemophilia A.
Starting date: 1st October 2020
My name is Himani Chand and I am from India. Being fascinated with the working of human body at molecular and cellular level, I decided to obtain my Bachelor’s degree in Biomedical Sciences. During that time, I developed a particular interest in studying biomedical data using computational methods. I went on to pursue my Master’s in Computational and Integrative Sciences from Jawaharlal Nehru University where I learnt how to organise and analyze omics data. My master’s project involved working with ChIP-seq NGS data and studying histone modifications and epigenetic profile in Yeast.
During my PhD, I will be working in Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano. Development of inhibitors against FVIII is one of the major treatment related risk factor in Hemophilia A patients. Therefore, the focus of my PhD will be using computational and bioinformatic tools and methods for immunoprofiling FVIII epitopes using High-throughput data of Hemophilia A patients. I will be looking at the inhibitor development against FVIII and studying the Anti-FVIII response.