Michela Deleidi

Our team investigates how genetic factors shape vulnerability and resilience to neurological
diseases. We are particularly interested in the mechanistic links between rare inherited
disorders and common age-related neurodegenerative diseases. By uncovering fundamental
biological pathways shared across these conditions, we aim to identify convergent mechanisms
that drive brain dysfunction and ultimately reveal new therapeutic opportunities.
Our research centers around three main directions:

• Understanding shared mechanisms between monogenic metabolic disorders and complex
neurodegenerative diseases.
We study how mitochondrial diseases, lysosomal storage disorders, and other rare genetic
conditions intersect with the pathophysiology of Alzheimer’s and Parkinson’s diseases.
Mitochondria represent a central theme in our work. We investigate how mitochondrial
dysfunction contributes to neuronal vulnerability, immune dysregulation, and altered
intercellular communication in neurodegeneration. By integrating genetic models of
mitochondrial disorders with organoid platforms and patient-derived iPSCs, we dissect how
impaired energy metabolism, defective mitophagy, and maladaptive mitochondrial stress
responses drive pathological changes shared across rare and common brain diseases. These
insights help explain why specific neuronal and glial populations are selectively affected in
neurodegeneration.

• Exploring the gut–brain–immune axis in neurodegeneration.
We examine why disorders that appear unrelated—such as inflammatory bowel disease or
chronic infections—display epidemiological and mechanistic links to Parkinson’s disease. In this
context, we aim to define how genetic traits influence host–pathogen interactions and shape
long-term brain health. We investigate how variants that enhance resistance to infection may
paradoxically predispose individuals to neurodegeneration later in life, revealing trade-offs
between immune defense and neuronal integrity.

• Developing advanced human model systems to study disease mechanisms.
A major technological focus of our lab is the generation of next-generation human models,
including brain organoids and multi-organ systems. We engineer long-term brain organoids that
recapitulate key aspects of human cortical and midbrain development, enabling the study of
neuronal maturation, microglial function, and early disease-associated changes with high
fidelity. In parallel, we are establishing gut–brain organ-on-chip platforms that integrate
intestinal epithelium, microbiome components, immune cells, and neural tissues within
dynamic microfluidic circuits. These systems allow us to investigate bidirectional
communication between the gut and the brain, model environmental exposures such as
pesticides, and uncover mechanisms linking peripheral inflammation, metabolic stress, and
neurodegeneration.

To address our biological questions, we combine these human model systems with induced
pluripotent stem cell (iPSC) technologies, single-cell transcriptomics, functional imaging, and
computational approaches. This integrated strategy enables us to dissect cellular and molecular

mechanisms underlying neurodegeneration across development, aging, and environmental
influence.