Our overarching goal is to identify epigenetic barriers and mechanisms that facilitate inner ear regeneration. Understanding the molecular events will inform strategies for stem cell replacement therapies and in situ regeneration. We employ stem cell-derived neurons and mouse models to elucidate the epigenetic changes that occur during auditory neuron regeneration. Using inner ear stem cell cultures, we identify changes in the epigenetic landscape as otic progenitors differentiate into different neuronal sub-types required for hearing. Using various mouse models, we genetically manipulate function of chromatin remodeling proteins to direct cell fate changes and facilitate regeneration. The molecular and cellular changes from stem cell cultures and inner ear tissues are evaluated using a multiomics approach by interrogating individual cells with both single cell RNA sequencing (scRNAseq) and single cell open chromatin assays (scATACseq). We complement this using different imaging paradigms to visualize the morphological changes. We collaborate with many other labs to support use of scRNAseq and super-resolution imaging. In particular, our work with Dr. Chris Pierce to examine epigenetic changes in the brain during addictive behaviors highlights our desire to explain complex behaviors at the molecular level.
Collaborators:
Epigenetics of Hearing Loss (NIDCD, R01DC18404, Multi-PI):
- Donna Martin (University of Michigan)
- Yehoash Raphael (University of Michigan)
Synthetic Transcription Factors for Regenerative Medicine (NIDCD, R01DC016612, Multi-PI):
- KiBum Lee (Chemistry and Chemical Biology, Rutgers)
Epigenetics of addictive disorders (NIDA, R01DA033641, Investigator)
- Chris Pierce (BHI, Rutgers)
Microscopy collaborators (NIH Shared Instrumention Grant, Multi-PI)
- Mike Kiledjian (CBN, Rutgers)
- Barth Grant (MBB, Rutgers)
- Victoria Abraira (CBN, Rutgers)
Zebrafish Development collaborators:
- Hatim Sabaawy (University of Colorado Cancer Center)
Single-cell sequencing collaborators:
- Jennifer Mulle (CABM, Rutgers)
- Zhiping Pang (CHI, Rutgers)
- Peng Jiang (CBN, Rutgers)
- Tetsuya Nakamura (Genetics, Rutgers)
- Kevin Monahan (MBB, Rutgers)