Three microscopy panels of a fruit fly's head, human cells and human neurons Exploring neurodegenerative disease mechanisms at the cellular level

The Zhang lab seeks to understand the molecular basis of neurodegeneration using Drosophila (fruit fly), human immortalized cell lines and human iPSC-derived neurons as models.

Overview

Big questions

Neurodegenerative diseases are a leading cause of death worldwide. Characterized by a gradual loss of the integrity and function of the nervous system, these diseases are age related, fatal, increasingly prevalent and incurable. A major challenge to the therapeutic development of these diseases is an incomplete understanding of their pathogenic mechanisms. Since the disease onset usually occurs at the end stage of pathogenesis when many cellular defects have emerged, it is unclear:

  • Which defect(s) may be the primary cause of diseases?
  • How do these defects interconnect to drive pathogenesis?

Addressing these questions requires a better understanding of how cells are organized and how they respond to genetic and environmental stress. Indeed, cellular stress responses play a critical role in aging and age-related diseases, including neurodegenerative diseases. Upon exposure to stress, cells or neurons acutely alter their physiological state to maintain homeostasis. However, chronic stress responses such as those that occur during aging may make these adaptive changes detrimental, thereby contributing to neurodegeneration.

With this notion, research in the Zhang lab seeks to address two big questions:

  • What is the molecular mechanism underlying neurodegeneration?
  • How do different cellular organelles and processes functionally connect?

Approaches

To address these questions, we have to rely on model systems. Different models offer different strengths and utilities. The advantage of the Zhang lab is the expertise to combine the power of Drosophila (fruit fly), human cell lines, mice and induced pluripotent stem cells (iPSCs) from patients as model systems. We use Drosophila and human cell lines to quickly identify potential disease mechanisms and then, verify our findings in mice and iPSC-derived neurons, as well as in patient postmortem tissues. With this strategy, we ensure the quickness, in vivo testing and patient-relevance of our studies.

About Dr. Zhang

Ke Zhang, Ph.D., is an assistant professor of neuroscience at Mayo Clinic College of Medicine and Science in Jacksonville, Florida. Dr. Zhang seeks to understand the molecular mechanisms underlying neurodegenerative diseases. Using Drosophila and patient iPSC-derived neurons as models, his team employs the power of genetics, cell biology, biochemistry, and neuroscience to decipher the pathogenic mechanisms of two related diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).