Description of Research Expertise

OUR RESEARCH INTEREST:
To better understand human brain complexity in health and disease, with the ultimate goal to uncover therapeutic targets for neurological disorders.

KEYWORDS:
Neurogenetics, neurodegeneration, neural development, epigenetics, Polycomb, protein homeostasis, lipids, cell therapies, stem cells, organoids, mouse models of disease.

RESEARCH SUMMARY:
The exponential increase of genetic studies over the last decades has uncovered numerous genetic variants associated to neurological disorders. Often, these variants are widely expressed in every tissue and yet, they exclusively disrupt development, function or viability of specific neural populations. Indeed, specific neuronal vulnerability is surprisingly common in many neurological diseases. But, why are some neurons vulnerable to disease stimuli, and why are others resistant? What determines the response of each neural type to divers physiological and pathological conditions? And how does each neural type acquire and maintain specialized functions? The major goal of our lab is to gain insights into these fundamental questions. To achieve this goal, our current research is focused on uncovering functional and molecular features of cerebellar and motor neurons. These neuronal populations are particularly vulnerable to ubiquitous stimuli that alter protein synthesis and degradation, and lead to perinatal neurodegenerative disorders (i.e. cerebellar ataxias and spastic paraplegias). Treatment strategies for these disorders are limited and focused to the management of symptoms that eventually progress to devastating conditions that impose far-reaching social and economic burden. By combining animal models and human stem cell derived cellular cultures, and interrogating them with sequencing, proteomic and imaging methods our lab is uncovering neuronal subtype particularities in health and disease to better understand human brain complexity and advance in neurological disease treatment options.

OUR RESEARCH APPROACH:
Our current focus is in the study of neurodevelopmental and degenerative disorders. We combine animal models and human stem cell derived cultures, and apply DNA/RNA sequencing, epigenomics, proteomics and imaging methods to gain insights into functional and molecular differences between resistant and vulnerable cells. Information that we gather from these studies will serve to better understand disease mechanisms and develop treatment strategies.

OUR PROJECTS:
1. The role of EZH1 in neural development and disease
2. Protein and lipid homeostasis in the control of human brain function and complexity
3. Mechanisms that lead to generation of neuronal diversity during brain development and are perturbed in neurological diseases
4. Development of high-throughput experimental platform for functional validation of novel genetic variants

LAB PERSONNEL:
Principal investigator: Naiara Akizu, PhD
Research assistant: Sunyimeng Lei and Kelsey Walsh
Postdocs: Thomas Roule, PhD,
Graduate students: Carolina Garcia-Diaz, Vanessa Sanchez, Lilly Ryll
Undergraduate students: Songyi Lee