Carlo Condello, PhD
Research Description
The major interest of my lab is to study the cellular and molecular biology of neurodegenerative diseases. My research program can be divided into 3 thematic areas: 1) We aim to understand the complex and dynamic role of glial cells, in particular microglia, and study their functional interactions with healthy and degenerating neurons. 2) We are focused on elucidating mechanisms of neuronal and glial vulnerability or resilience to aberrant protein accumulation (proteinopathy) as found in Alzheimer's disease (AD) and related disorders (ADRDs). 3) My lab is studying the kinetics, toxicity and conformational heterogeneity of pathogenic protein self-assemblies causing AD and ADRDs. Because of these interests, I have recruited a diverse team of scientists to my lab and established several collaborations with chemists, structural biologists, bioengineers, and neurobiologists to pursue these interconnected topics.
To reveal biological mechanisms of protein aggregation, neurodegeneration, and innate immunity (microglia biology), we employ an interdisciplinary approach including cell and molecular neuroscience, biophysics, chemical biology and systems biology methods. Often, we innovate new imaging approaches and model systems to illuminate complex neurobiological phenomena not easily studied with conventional methods. We employ genetic and pharmacological manipulations to define cause and effect relationships in mouse and rat models. In tandem, we study genetic risk factors (e.g., TREM2 and CSF1R mutants) and human biology of disease using patient brain samples and human cell lines to inform and validate discoveries made in our rodent models.
In summary, the Condello lab is a multidisciplinary laboratory with strong collaborations across multiple departments pursuing topics ranging from basic to translational neuroscience. We are driven to discover mechanisms, biomarkers, and therapeutics for neurodegenerative disease. I believe this to be an exciting and strong research environment to train the next generation of neuroscientists and biomedical researchers.
Current Projects
- Mechanisms of selective vulnerability of neurons to tauopathy and development of novel tools to study kinetics of tau deposition.
- Mechanisms of microglial-mediated sex-based differences in tauopathy
- Structural and biochemical characterization of tau conformational strains targeting specific neural cell types and causing distinct tauopathies
- Cell biology, biophysics and genetics of innate immune receptors in microglia and their roles in brain aging and neurodegeneration
- Precision pharmacological targeting of CSF1R to selectively inhibit disease-driving microglia in tauopathy
- Characterizing the biological consequences of CSF1R mutations causing the rare neurodegenerative disease, ALSP (Adult-onset Leukoencephalopathy with Axonal Speroids and Pigmented Glia) and evaluating in vivo efficacy of CRISPR-edited cell replacement.
- Role of microglia in axonal spheroid formation and myelin degeneration dependent and independent of neurodegenerative pathology
- Elucidating the in situ relationships between lipidome dysregulation, APOE, and oligodendrocyte vulnerability in Alzheimer’s disease
Lab Members
Ian Steele; Stephanie Huard; Erika Castillo, PhD; Julio Leon, PhD; Hyun-Jun Yang, PhD; Henry Pan, PhD; Chaitali Anand, PhD; Miranda Sullivan; Emily Graham
List of your academic community service:
NS201B Lecturer, NS219 Scientific Writing Group Leader, QBC Journal Club Mentor, PSPG Seminar Series committee, IMSD Mentor, BMS 1st year Faculty Advisor, IND, ad hoc study section member in NIA and NINDS review panels for R and F awards.