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Tianyu Cao (曹天雨)

(he/him)

Postdoctoral Fellow

Johns Hopkins School of Medicine

Wong Lab

My research focuses on developing splicing-based therapies for TDP-43–related neurodegeneration. In Prof. Philip Wong’s lab at Johns Hopkins, I study how TDP-43 loss of function leads to cryptic exon inclusion and contributes to neurodegeneration. A major focus of my work is a chimeric therapeutic protein (CTR) that restores TDP-43 splicing repression without aggregation risk. Using AAV-based delivery in mouse models, I have demonstrated neuronal rescue, behavioral restoration, and cryptic exon repression. I am now advancing this approach toward human-compatible delivery using transferrin receptor–targeted AAV capsids.

My long-term goal is to become an independent investigator developing splicing-based therapies for ALS and frontotemporal dementia (FTD), while uncovering how TDP-43 dysfunction intersects with tau and α-synuclein pathology.

eRA Commons: Tianyu | Lab: Wong Lab | Department: Department of Pathology, Johns Hopkins School of Medicine

Google Scholar · ORCID · GitHub · Email: tcao6@jh.edu

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Education

Postdoctoral Fellow, Department of Pathology

2023-07-01

Johns Hopkins School of Medicine

Research Trainee, Department of Pathology

2019-09-01
2021-06-30

Johns Hopkins School of Medicine

M.D. and Residency, Clinical Science of Integrative Medicine

2018-09-01
2023-06-30

Beijing University of Chinese Medicine

B.M., Medicine

2013-09-01
2018-06-30

Beijing University of Chinese Medicine

Exchange Student, School of Biological Science

2015-01-01
2015-06-30

Nanyang Technological University

Research Interests

TDP-43 & Cryptic Exon Biology AAV-based Gene Therapy ALS / Frontotemporal Dementia Splicing-based Therapeutics Multi-proteinopathy (Tau / α-Synuclein)

🔬 Research

My research centers on understanding and treating TDP-43–mediated neurodegeneration through three interconnected themes:

TDP-43 & Cryptic Exon Biology

TDP-43 is an essential RNA-binding protein whose loss of function leads to the inappropriate inclusion of cryptic exons — normally silenced sequences that, when expressed, cause mRNA degradation or production of toxic proteins. I study the mechanisms by which TDP-43 depletion drives cryptic exon inclusion and how this process contributes to neuronal vulnerability and death in diseases like ALS and frontotemporal dementia (FTD).

AAV-based Gene Therapy for ALS/FTD

A major focus of my work is the development of a chimeric TDP-43 repressor (CTR) — an engineered therapeutic protein that restores TDP-43’s splicing repression function without the risk of aggregation. Using adeno-associated virus (AAV) vectors, I have demonstrated broad brain biodistribution, neuronal rescue, behavioral restoration, and cryptic exon repression in mouse models of FTD. I am now advancing this approach toward human-compatible delivery using transferrin receptor–targeted AAV capsids.

Multi-proteinopathy & Tau/α-Synuclein

Neurodegenerative diseases rarely involve a single pathological protein. I investigate how TDP-43 dysfunction intersects with tau and α-synuclein pathology — exploring whether loss of TDP-43 function sensitizes neurons to tau-mediated toxicity and how these co-pathologies contribute to the clinical heterogeneity seen in diseases such as Alzheimer’s disease and Lewy body dementia.

📄 Publications