Research

Oligodendrocytes are the myelinating glia cells of the brain, allowing fast conduction of action potentials among neurons, thus imperative for proper neurological functions. The major goal of the research in the Nobuta lab is to develop regenerative therapies for human oligodendrocyte disorders such as leukodystrophies, multiple sclerosis, and white matter injury associated with premature birth. The lab takes two approaches to achieve this goal: 1) gaining fundamental knowledge in human oligodendrocyte development extracting data directly from human cells and tissues, and 2) engineering transplantable human oligodendrocytes by direct lineage conversion.

Hiroko Nobuta awarded NIH R21 grant April 2023: The grant investigates the function of human oligodendrocyte sub-populations. This grant is in collaboration with Zhiping Pang (Rutgers University) and Kosaku Shinoda (Albert Einstein School of Medicine).

Gaining fundamental knowledge in human oligodendrocyte development.

The vast majority of our knowledge in oligodendrocyte biology is derived from mouse models. Despite significant advances in mouse oligodendrocyte knowledge, no effective therapies have been translated to human oligodendrocyte disorders. To close the knowledge gap, our lab uses transcriptomic analysis comparing mouse and human oligodendrocytes to identify human specific oligodendrocyte populations. Obtained information will be used to study the function of human oligodendrocytes using imaging, genetics, and electrophysiological techniques.

Engineering transplantable human oligodendrocytes.

Oligodendrocytes are considered a great candidate for cell-based transplantation therapy because of their ability to regenerate the damaged myelin. However, no method exists to generate autologous, transplantable human oligodendrocytes at high quantity and safety. Our lab will establish an alternative method for human oligodendrocyte production by direct lineage conversion of human dermal fibroblasts (skin cells) using transcription factor-based cellular reprogramming. We will optimize the engineering protocol to generate highly efficient, transplantable oligodendrocytes for clinical application. Furthermore, we will use the engineered oligodendrocyte system to develop a cost- and time- effective drug screening platform for oligodendrocyte disorders. The platform will fast-forward disease modeling, drug discovery, and personalized treatment for oligodendrocyte disorders.