Established in 2020 by the Embassy of Italy in Washington D.C., the 2023 edition recognizes young Italian researchers in the USA providing fundamental contributions to the understanding and curing of neurodegenerative diseases including those related to aging.
We are thrilled to congratulate the outstanding finalists of the 2023 edition: Francesca Garretti, Roberta Peruzzo, and Simone Brioschi.
Learn about their exciting and innovative research they presented at the Symposium on October 19, 2023 to the Jury chaired by Prof. Alessandro Sette, La Jolla Institute for Immunology. The video of the Symposium webinar is available at https://youtu.be/cfonGUxtQEs?si=8aSHkZZMg14DUNLQ.
The winner will be announced at ISSNAF 2023 Annual Event in Washington D.C. on November 8.
Francesca is a Postdoctoral Fellow in the laboratory of Alison Goate in the Loeb Center for Alzheimer’s disease at the Icahn School of Medicine at Mount Sinai in New York. Her research focuses on investigating the effects of genetic risk factors associated with Alzheimer’s disease on induced pluripotent stem cell derived microglia function. She completed her PhD in Pathobiology and Molecular Medicine at Columbia University where she was co-mentored by Dr. David Sulzer and Dr. Dritan Agalliu. During her PhD, she uncovered alpha-synuclein autoimmunity driven by T cells and specific immune alleles in Parkinson’s disease (PD) patients. In addition, she modeled alpha-synuclein autoimmunity in mice to show that it is a driver for enteric inflammation and neurodegeneration and prodromal symptoms of PD. She received her BSc with honours in Biochemistry from the University of St. Andrews, UK and MSc in Biomedical Sciences at the Icahn School of Medicine at Mount Sinai. Francesca has co-authored 8 peer-reviewed publications that have been cited over 800 times and has given numerous invited talks and seminars. She currently holds an F32 Kirschstein-NRSA fellowship from the National Institute of Aging.
Apolipoprotein E isoform 4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease. Despite the strong effect of APOE4 on AD risk, a wide range of clinical outcomes exist within APOE4 carriers: some can develop cognitive impairment as early as 30 years of age while other carriers remain cognitively normal beyond 100 years. The large range in clinical manifestation suggests that there are genetic variants that modulate APOE-associated risk. To investigate this hypothesis, we conducted stratified genome-wide association studies of APOE4 carriers at the extremes of age at onset distribution to identify variants that modify risk. We identified a single variant in EIF2B3 encoding the amino acid substitution S404A as a candidate risk modifier. eIF2B3 is a subunit of eIF2B, a guanine exchange factor (GEF) for eIF2 that is involved in translational control and the integrated stress response (ISR). My research focuses on understanding the role of APOE genotype on ISR and the effect of eIF2B3-S404A mutation in human microglia function. Work here has the potential to not only greatly impact public health through the validation of a novel AD risk modifier, but also significantly enhance our understanding of how AD variants may impact microglial cell function and modulate AD risk.
I attribute my professional trajectory to the excellent mentorship and guidance that I have been fortunate to receive throughout my undergraduate and graduate career. As such, I am passionate about returning my knowledge by mentoring young scientists. During my postdoc, I have had the opportunity to work with several associate research scientists and PhD students. In addition, I have worked with one student from the Bronx Science High School who is competing in the Regeneron Science Talent Search competition for the past two summers. In both instances, I have been astonished by the mentee’s scientific acumen and have felt rewarded by their advances in knowledge. I plan on continuing to mentor younger scientists in the future.
Roberta studied Molecular Biology at the University of Padova (Italy), where she completed her bachelor’s and master’s` Degree in 2013 and 2015 respectively.
After a year as a postgraduate researcher in which she delved into mitochondrial studies, Roberta pursued a Ph.D. in Biosciences at the University of Padova and obtained her degree in 2020. Working in Prof Ildikò Szabò’s laboratory, she investigated how mitochondrial ion homeostasis impacts cell viability and how its modulation via pharmacological tools can be used to treat neurological and metabolic diseases. Her discovery was patented in 2021.
In 2021, Roberta was awarded the AIRC (Italian Association for Cancer Research) Fellowship and joined Prof Roberto Zoncu’s laboratory at the University of California Berkeley for her postdoctoral studies. Here, she applied her expertise to a different organelle, the lysosome, and shifted her research emphasis on neurodegenerative diseases driven by lysosomal dysfunction. Specifically, Roberta is combining different approaches to determine how the master regulator, mTORC1 kinase, regulates autophagy, a lysosome-dependent pathway defective in multiple neurodegenerative diseases. Moreover, she is developing innovative chemical biology approaches to enhance the ability of autophagy and lysosomes to degrade neurotoxic protein aggregates.
Roberta’s research has addressed critical aspects of both mitochondrial and lysosomal dysfunction. By studying these organelles’ homeostasis, her research is trying to find innovative therapeutic strategies to tackle different diseases.
Her Ph.D. work pioneered the idea of using redox cyclers as a novel therapeutic approach against mitochondrial disorders and laid the foundations for expanding their therapeutic horizon to other diseases characterized by mitochondrial deficiency, such as Parkinson's disease.
Currently, she is pursuing an intriguing project aimed to counter autophagic escape of toxic protein aggregates in ALS/FTD. Autophagy mediates elimination of aggregated proteins and damaged organelles by recognizing and delivering them to the lysosomes, where macromolecular degradation occurs. As such, autophagy is crucial in neuronal development and function, and its impairment has been implicated in the pathology of neurodegeneration. By engineering chemical recruiters, Roberta’s current project aims to induce the delivery of cytotoxic aggregates to lysosomes, enhancing their degradation. These findings will pave the way for the development of new-generation compounds with implications for ALS/FTD treatment, as well as other proteinopathies.
Roberta’s research represents a critical step forward in the development of innovative treatments for disorders characterized by mitochondrial and/or lysosomal dysfunction, holding significant promise for the field of neurodegenerative research.
Roberta enjoys mentoring and teaching students and tries to pass on her passion for science. She gave lectures to undergraduate students on Bioenergetics within the university course of Biochemical Methodologies. She serviced as Teacher assistant from 2016 to 2020 at the University of Padova. In addition, she supervised five bachelor students and five master students during their internships at the University of Padova and the University of California Berkeley.
During my postdoc I conducted a seminal study describing composition and origin of meningeal B cells in health and aging. This research showed that skull-derived B cells infiltrate the meninges at initial stages of their development (pro-B and pre-B cells) and locally accomplish their differentiation process. By contrast, blood-derived age-associated B cells (ABCs) accumulate in the mouse meninges during aging. We proposed that meningeal adaptive immunity is tailored to the local antigen repertoire to maintain immune privilege within the CNS. As a future study, I propose to investigate the composition and clonality of meningeal B cells in models of autoimmunity, like Lupus. Alongside, I generated a novel Cre line targeting microglia and BAMs specifically after the infiltration of the brain rudiment. I used this tool to delete the transcription factor SMAD4 in microglia and BAMs during early stages of embryonic brain development. Deletion of SMAD4 impaired microglia specification, producing broad transcriptomic changes and epigenetic remodeling. By contrast, BAM specification program was unaffected. Furthermore, mice with SMAD4-deficient microglia exhibited impaired learning and memory skills, indicating that a physiological microglia maturation during embryonic development is crucial for brain functions. I am currently investigating the role of PU.1 in microglia during amyloid pathology.
I study brain and meningeal immunity. Specifically, I want to understand how brain immune cells develop and communicate with their local microenvironment. My main focus is “microglia”, the brain resident macrophages, which play important roles in the development and homeostasis of this organ. Furthermore, microglia are involved in virtually all brain diseases, including Alzheimer’s. Microglia solely derive from the embryonic hematopoiesis and receive no input from the bone marrow. Additionally, microglia have a unique phenotype, determined by the selective expression of genes which are not active in other immune cells. This suggests a highly specific function of microglia compared with macrophages from other compartments. For instance, microglia operate a fine-tuning of neuronal activity interacting with synapses and regulate the development of the brain white matter. Importantly, perturbation of microglia development can cause detrimental effects on the brain, ranging from neurodevelopmental alterations, cognitive deficits, and neurodegeneration. Thus, microglia have paramount importance for the brain's physiology and function under steady state as well as during brain diseases. My overarching goals are to understand how microglia develop, how they change and what they do during brain disease, and whether genetic polymorphisms linked to brain disorders affect the development and function of these cells.
My wife and I moved to Washington University in St Louis in winter 2018. I joined the lab of Dr. Marco Colonna to study the mechanisms of CNS immunity during brain diseases, especially neurodegenerative disorders like Alzheimer’s Disease. During this period, I have acquired extensive expertise and skills which allowed me to publish two high-impact studies in top journals. This professional experience in the US has been incredibly rewarding and helped me develop a strong background in neuroscience and immunology. I am currently developing high profile projects and trying to pursue my line of research as an independent scientist.