ASOs.
Antisense oligonucleotides (ASOs) for the therapeutics of Mendelian diseases: what if we went from therapeutic modality to addressable diseases, instead of the other way around? With the Yu Lab at Boston Children’s Hospital, which pioneered of N=1 medicine developing Milasen, I have designed a computational pipeline and optimized a strategy for ASO design. This study is also supporting previously understudied aspects of gene regulation. The manuscript will be out hopefully in a year.
Omics.
Statistical modeling of multiomic single-cell data for the systematic study of deficits in neurodevelopment: this will be the broad topic of my doctoral studies with the La Manno Lab at EPFL.
Longevity, genetic disease, mitochondria
Longevity pathways
WGCNA analysis of a longitudinal RNA-seq dataset of the short-lived fish N. furzeri to infer pathways predictive of lifespan: with the Cellerino Lab in Pisa, I developed a pipeline combining a few network metrics with more conventional RNA-seq analysis and found a novel pathway strongly predictive of slower aging. In the long run, intervening on such pathway might be a strategy to prolong lifespan.
Mitochondrial RNA import
A reporter to prove the import and translation of cytosolic RNAs into mitochondria: with the Cremisi Lab in Pisa, we are trying to demonstrate the highly debated import of RNAs from the cytosol into the powerhouse of the cell. If we were able to do so unequivocally, we may try to design gene compensation therapeutics by mitochondrial import of RNAs to help fight mitochondrial diseases.
Genetic diseases
Modeling of the neurodevelopmental disorders and ASO design: with the Yu Lab, I’m analyzing scRNA-seq data from patient-derived and isogenic control brain organoids to discover disease signatures.
Top bio questions that captivate me
How do environmental factors and genetic variants affect neurodevelopment? How does this change in disease settings?
What are the omics underpinnings of trauma, memory formation, emotions, recalling, depression, serenity, or anxiety?
What are the molecular underpinnings of well-being and emotions? How do diet, exercise, sleep, meditation, and behaviors in general mechanistically affect our body and perception of well-being? What are the dimensions of animal consciousness and how do they vary across taxa?
How can we systematically address idiopathic conditions to discover their mechanisms?
What is the effect of single mutations at the level of protein/RNA, cell, organ and body? Are they predictable under some complex model? What are the determinants of a loss-of-function versus a gain-of-function?
What happens when we and other animals die in sleep without any obvious health issue?
Top biotech questions that captivate me
How can we interrogate libraries of ASOs to determine the mechanisms underlying their efficacy and predict their toxicity?
How can we develop holistic measures of cell toxicity and organismal toxicity for any personalized genomic medicine (ASOs, base editors, prime editors…)?
How can we make automatic, high-throughput, easy-to-perform proteomics (an “equivalent” of PCR)?
Can we establish routine screenings to diagnose cancers at a stage when they are curable?
Can we create diagnostics and prognostics measures for several health-related conditions and diseases from blood biopsies all at once?
Can we get biopsies from distal organs through the blood?
Can we extend our health-span and/or lifespan?
How can we create statistical frameworks for N-of-1 trials? How can we find the most likely factors contributing to one’s health or pathology to better direct therapeutics?
How can we non-invasively deliver biological therapeutics to cells in a very specific cell state?
Can we map in real time several omic signals in a living and behaving animal, such as the spatial distribution of several neurotransmitters while an animal behaves freely?
How can we use to our best transcriptome-based technologies to design the next wave of tools for diagnosis, prognosis, monitoring, and treatment personalization?
Can we finely map extracellular solutes at very low concentrations?
How can we rescue mitochondrial defects, in mitochondrial diseases and in aging?
How can we establish objective metrics to quantify behaviors and relate them with molecular variables?
How can we make easy-to-use, field deployable vaccines and diagnostics for developing countries?
How can we advance interventional genomics to make it so safe and effective to be routine as much as bone surgery?
Can we make advanced wearable diagnostic tools to protect us from several health threats?
Can we make AI-based generative models of virtual patients that from a given patient’s genome and environment data understand their vulnerabilities to disease or give health-related advice?
How can we make a vaccine for HIV and other hard-to-vaccinate viruses and bacteria? How can we make effective vaccines for several cancers?