Dr. Chu is Director of the Ophthalmic Pathology Service in the Division of Neuropathology and Co-Director of the Pathologist Investigator Residency/Research Training Program. As principal investigator, she directs a basic research program focused on synapto-dendritic remodeling and organelle (mitochondria, autophagy/lysosome, Golgi) homeostasis in Parkinson's disease and frontotemporal dementias. She is part of the training faculty for the Pathology and Neuroscience Graduate programs, the MSTP and the PSTP. She is a member of the Center for Protein Conformation Diseases, the Center for Neuroscience and the Pittsburgh Institute for Neurodegenerative Diseases.
Clinical Expertise
Dr. Chu is director of the ophthalmic pathology service. For information on submitting specimens, visit the Eye Consults page. For information on training in academic neuropathology or ophthalmic pathology, visit the Neuropathology website.
Research Interests
Cell Biology of Neurodegenerative Diseases
Dr. Chu's research focuses on mechanisms of neurodegeneration and neuroprotection in Parkinson's disease with dementia and frontotemporal dementias. A major focus is delineating why adaptive cellular mechanisms fail to protect neurons, with an emphasis on mitochondrial dysfunction, cellular quality control and kinase signaling. Molecular imaging and biochemical studies employing primary neuron cultures, iPSC-derived neurons, patient-derived samples and transgenic mice are utilized to study the role of dysregulated cell signaling, proteostasis, autophagy and mitochondrial pathobiology in genetic models of neurodegeneration, with an emphasis on protein-protein interactions and organelle biology. We are particularly interested in potentially reversible mechanisms by which mutations in PD-linked genes affect dendritic extension/retraction and synaptic dysfunction.
Current areas of interest include:
- Genetic and iPSC models of neurodegenerative diseases (PINK1, VCP, MAPT, KIF1A, POLG)
- Mitochondrial quality control, protein homeostasis, and calcium dysregulation in dendritic morphogenesis and spine remodeling
- Protein-protein interactions and organelle transport in axons and dendrites
Techniques
Protein biochemistry, molecular cell biology, mass spectrometry and phospho-proteomics, quantitative RT-PCR, immunochemistry, multi-label confocal microscopy, live cell imaging, electron microscopy, stereotactic brain injections, RNA interference.
Educational Initiatives
Dr. Chu is a member of the Graduate Programs of Cellular and Molecular Pathology (CMP) and Center for Neuroscience (CNUP), the Medical Scientist Training Program (MSTP) and the Physician Scientist Training Program (PSTP). She is committed to career development of pre-doctoral, post-doctoral and physician-scientist trainees, developing and directing for 10 years a MSTP Professional Development course focused on grant writing and peer-review, which is now emulated by other MSTP and graduate programs nationwide. She is founding co-director for the Pathologist Investigator Residency/Research Training Program. This "PI-training track" is designed to develop the next generation of physician-scientist leaders, independently-funded Academic Pathologists pursuing combined research and diagnostic careers.
Representative Publications
Selected Research Articles
H Homayoun, MR DeChellis-Marks, J Kofler, G Fricklas, AG Gleixner, FC Yeh, D Lacomis, CT Chu*, CJ Donnelly*. Novel kinesin family member 1A variants linked to atypical parkinsonism elicit altered neuronal transactive response DNA binding protein 43 kDa interactions and dendritic atrophy. Am J Pathol Accepted, in press. *Co-senior authors. https://doi.org/10.1016/j.ajpath.2025.05.018
M Verma*, L Francis*, BN Lizama*, J Callio, G Fricklas, KZQ Wang, BA Kaufman, L D’Aiuto, DB Stolz, SC Watkins, VL Nimgaonkar, A Soto-Gutierrez, A Goldstein & CT Chu. (2023) iPSC-derived neurons from patients with POLG mutations exhibit decreased mitochondrial content and dendrite simplification. Am J Pathol 193: 201-212. *Co-first authors. https://www.sciencedirect.com/science/article/pii/S0002944022003601?via%3Dihub
PA Otero, G Fricklas, A Nigam, BN Lizama, ZP Wills, JW Johnson & CT Chu. (2022) Endogenous PTEN-induced kinase 1 regulates dendritic architecture and spinogenesis. J Neurosci 42: 7848-7860. https://www.jneurosci.org/content/42/41/7848.long
Y Liu, TB Lear, M Verma, KZQ Wang, PA Otero, AC McKelvey, SR Dunn, E Steer, NW Bateman, C Wu, Y Jiang, NM Weathington, M Rojas, CT Chu*, BB Chen*, RK Mallampalli*. 2020. Chemical inhibition of Fbxo7 reduces inflammation and confers neuroprotection by stabilizing the mitochondrial kinase PINK1. JCI Insight 5: e131834. *co-senior authors, equal contributions. https://insight.jci.org/articles/view/131834
M Verma, J Callio, PA Otero, I Sekler, ZP Wills & CT Chu. (2017) Mitochondrial Ca2+ dysregulation contributes to dendrite degeneration mediated by PD/LBD-associated LRRK2 mutants. J. Neurosci 37: 11151-65. https://www.jneurosci.org/content/37/46/11151.long
CT Chu, J Ji, RK Dagda, JF Jiang, YY Tyurina, AA Kapralov, VA Tyurin, N Yanamala, IH Shrivastava, D Mohammadyani, KZQ Wang, J Zhu, J Klein-Seetharaman, K Balasubramanian, AA Amoscato, G Borisenko, Z Huang, AM Gusdon, A Cheikhi, EK Steer, R Wang, C Baty, S Watkins, I Bahar, H Bayır & VE Kagan (2013) Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nature Cell Biol 15:1197-1205. https://www.nature.com/articles/ncb2837
Selected Books, Reviews, and Clinical Articles
CT Chu. (2025) The role of autophagy in excitotoxicity, synaptic mitochondrial stress and neurodegeneration. Autophagy Rep. 4:1, 2464376. https://doi.org/10.1080/27694127.2025.246437
CT Chu. (2022) Mitochondria in neurodegeneration. Curr Opin Physiol. 26: 100532.
CT Chu. (2019) Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases. Neurobiol Dis 122: 23-34. https://pmc.ncbi.nlm.nih.gov/articles/PMC6396690/
E Franco, M Gagrani, HL Scanga, RG Areaux, CT Chu* & KK Nischal. 2024. Variable phenotype of congenital corneal opacities in biallelic CYP1B1 pathogenic variants. Cornea 43: 195 200.
O Lopes Abath Neto, ZA Koretz, AI Wald, PP Rath, M Nikiforova & CT Chu. 2022. Molecular profiling of renal cell carcinoma presenting as iris metastasis. Am J Ophthal Case Reports 27: 101599.
2010 Carnegie Science Awards Profile of Dr. Chu's Research