Project Description

Emerging studies have shown that epigenetic alternations underlie a wide range of neurological diseases spanning from neurodevelopmental disorders (e.g., autism) to neurodegenerative disorders (e.g., Alzheimer’s disease and other dementia). It is found that changes in epigenetic landscape, impaired neuronal excitability and activation of microglia could be convergent mechanisms of these otherwise very different diseases. Indeed, it is recently discovered that genetic mutations in a key epigenetic gene DNMT1, lead to devastating disease symptoms including dementia, neuropathy, and seizures of affect patients. However, the disease mechanisms are unknown. Yang lab and Yuan lab have established multiple mouse models, iPSCs derived neurons/organoids and microglia models to study the interactions of neurons and microglia underlying these disease phenotypes. Questions to be addressed includes: what’s the role of microglia in the maladaptation of altered firing of neurons? What are the neurons or microglia specific epigenetic changes that can be identified in the disease models? Can epigenetics factors by targeted to alleviate these diseases? Combining the expertise from both labs, cutting-edge technology including CRISPR mediated activator and inhibitors, single-cell RNA-sequencing and spatial transcriptomics, high-density in vitro and in vivo electrophysiology, optogenetics and chemogenetics will be used to tackle these questions

Start Date

05/01/2022

Postdoctoral Qualifications

Ideal candidate should have a background in neuroscience, molecular biology, bioengineering or physiology. We welcome candidate who is motived to learn new skillsets, and is enthusiastic about multidisciplinary research.

Co-Advisors

Chongli Yuan, Davidson School of Chemical Engineering, https://engineering.purdue.edu/ChE/people/ptProfile?resource_id=65069
Yang Yang, Medicinal Chemistry and Molecular Pharmacology, https://www.yangyanglab.org/

Outside Collaborators

Bill Skarnes, the Jackson Laboratory

Bibliography

Jingliang Zhang, Xiaoling Chen, Muriel Eaton, Jiaxiang Wu, Zhixiong Ma, Shirong Lai, Anthony Park, Talha S. Ahmad, Zhefu Que, Ji Hea Lee, Tiange Xiao, Yuansong Li, Yujia Wang, Maria I. Olivero-Acosta, James A. Schaber, Krishna Jayant, Chongli Yuan, Zhuo Huang, Nadia A. Lanman, William C. Skarnes, Yang Yang*, Severe deficiency of voltage-gated sodium channel Nav1.2 elevates neuronal excitability in adult mice. Cell Reports. 2021 in press
Eaton M, Que Z, Zhang J, Beck K, Shi R, McDermott J, Ladisch M*, Yang Y*, Multi-electrode array of sensory neurons as an in vitro platform to identify the nociceptive response to pharmaceutical buffer systems of injectable biologics. Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists. 2021 in press
Mendonca A, Sánchez OF, Xie J, Carneiro A, Lin L, Yuan C. Identifying distinct heterochromatin regions using combinatorial epigenetic probes in live cells. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 2021;1864(8):194725.
Sánchez OF, Mendonca A, Min A, Liu J, Yuan C. Monitoring Histone Methylation (H3K9me3) Changes in Live Cells. ACS Omega. 2019;4(8):13250-9.