Chien-Ting Wu, Ph.D.

The airway epithelium is the initial site of entry for respiratory pathogens into the human body. Respiratory tissues have evolved a mucus clearance system that acts as a physical, innate defense mechanism. This structure, composed of the ciliated epithelial cells, basal cells, and mucus-producing goblet cells, creates an extracellular barrier that limits passage of inhaled foreign matter and effectively clears trapped material through coordinated ciliary beating. The extracellular barrier in the mucosal surface is comprised of a mucus layer, which sits on top of the ciliary brush, and an underlying periciliary layer (PCL). These structures permit particles smaller than 40 nm, such as adeno-associated viruses (∼25 nm), to penetrate the PCL, whereas larger adenovirus particles (∼100 nm) are excluded from the PCL. However, many respiratory viruses as large as 100 nm in diameter (e.g., influenza, SARS-CoV-2) bypass both the mucus layer and the PCL to infect airway epithelial cells. This begs the question of how viruses subvert the nasal mucosa for cellular entry, replication, and egress. Dr. Wu long-term research interest is to decipher the molecular mechanism of (1) respiratory pathogen entry and egress and the downstream signaling pathways these viruses use to circumvent innate immunity in the airway epithelium, (2) virus infection-induced tumorigenesis in upper aerodigestive tract, and (3) how metabolic disorders increase susceptibility to severe infectious disease. The proposed research is innovative and may uncover novel pharmacological targets for upper aerodigestive tract infection and cancer.

Dr. Wu's research program builds on my prior scientific accomplishments and training. Dr. Wu has a strong scientific background in developmental biology, virology, metabolism, and cancer biology. My training is in molecular and cell biology, biochemistry, mouse genetics and physiology, and multi-omic technologies. Dr. Wu's prior research experiences share the common thread of elucidating the detailed molecular mechanism of how signaling pathways facilitate virus infection, activate host antiviral immune response, and regulate basic cellular processes with relevance to human health. Dr. Wu's previous discoveries have instigated several new projects with meaningful therapeutic implications. Dr. Wu has therefore the necessary expertise as well as the drive and creativity to successfully carry out the proposed research project.

Bio

Postdoc: Stanford University

Graduate School: Academia Sinica, Interdisciplinary Neuroscience

Undergraduate: National Yang-Ming University, School of Medicine

• The development of nasal epithelium
• The interaction between metabolism and immunity
• Virus infections-induced tumorigenesis in upper aerodigestive tract
• Virus-host interaction in nasal and oral epithelium

Featured Publications

SARS-CoV-2 replication in airway epithelia requires motile cilia and microvillar reprogramming

Chien-Ting Wu1, 11, Peter V. Lidsky2, 11, Yinghong Xiao2, 11, Ran Cheng1, 3, 11, Ivan T. Lee4, 5, 6, Tsuguhisa Nakayama6, 7, Sizun Jiang4, Wei He1, Janos Demeter1, Miguel G. Knight2, Rachel E. Turn1, Laura S. Rojas-Hernandez8, Chengjin Ye9, Kevin Chiem9, Judy Shon10, Luis Martinez-Sobrido9, Carolyn R. Bertozzi10, Garry P. Nolan4, Jayakar V. Nayak4, 6, Carlos Milla8, Raul Andino2, *, Peter K. Jackson1, 4, 12, * Cell (in revision) 2022

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.

Nakayama T, Lee IT, Jiang S, Matter MS, Yan CH, Overdevest JB, Wu CT, Goltsev Y, Shih LC, Liao CK, Zhu B, Bai Y, Lidsky P, Xiao Y, Zarabanda D, Yang A, Easwaran M, Schürch CM, Chu P, Chen H, Stalder AK, McIlwain DR, Borchard NA, Gall PA, Dholakia SS, Le W, Xu L, Tai CJ, Yeh TH, Erickson-Direnzo E, Duran JM, Mertz KD, Hwang PH, Haslbauer JD, Jackson PK, Menter T, Andino R, Canoll PD, DeConde AS, Patel ZM, Tzankov A, Nolan GP, Nayak JV, Cell Rep Med 2021 Oct 2 10 100421

Discovery of ciliary G protein-coupled receptors regulating pancreatic islet insulin and glucagon secretion.

Wu CT, Hilgendorf KI, Bevacqua RJ, Hang Y, Demeter J, Kim SK, Jackson PK, Genes Dev 2021 09 35 17-18 1243-1255

SARS-CoV-2 infects human pancreatic ? cells and elicits ? cell impairment.

Wu CT, Lidsky PV, Xiao Y, Lee IT, Cheng R, Nakayama T, Jiang S, Demeter J, Bevacqua RJ, Chang CA, Whitener RL, Stalder AK, Zhu B, Chen H, Goltsev Y, Tzankov A, Nayak JV, Nolan GP, Matter MS, Andino R, Jackson PK, Cell Metab 2021 08 33 8 1565-1576.e5

ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs.

Lee IT, Nakayama T, Wu CT, Goltsev Y, Jiang S, Gall PA, Liao CK, Shih LC, Schürch CM, McIlwain DR, Chu P, Borchard NA, Zarabanda D, Dholakia SS, Yang A, Kim D, Chen H, Kanie T, Lin CD, Tsai MH, Phillips KM, Kim R, Overdevest JB, Tyler MA, Yan CH, Lin CF, Lin YT, Bau DT, Tsay GJ, Patel ZM, Tsou YA, Tzankov A, Matter MS, Tai CJ, Yeh TH, Hwang PH, Nolan GP, Nayak JV, Jackson PK, Nat Commun 2020 10 11 1 5453

Identifying natural compounds that potently inhibit SARS-CoV-2 in mouse models

Junjiao Yang1, 2, #, Yinghong Xiao3, #, Peter V. Lidsky3, #, Chien-Ting Wu4 , Luke R. Bonser5 4 , Shiming Peng1 , Miguel A. Garcia-Knight3 , Michel Tassetto3 , Chan-I Chung1, 2, Xiaoquan Li1, 2 5 , Tsuguhisa Nakayama6 , Ivan T. Lee7 , Jayakar V. Nayak6 , Khadija Ghias5 , Kirsten Hargett5 6 , Brian K. Shoichet1 , David J. Erle5 , Peter K. Jackson4 , Raul Andino3, *, Xiaokun Shu1, 2, * Nature Microbiology (In press) 2022

A defective viral genome strategy elicits broad protective immunity against respiratory viruses.

Xiao Y, Lidsky PV, Shirogane Y, Aviner R, Wu CT, Li W, Zheng W, Talbot D, Catching A, Doitsh G, Su W, Gekko CE, Nayak A, Ernst JD, Brodsky L, Brodsky E, Rousseau E, Capponi S, Bianco S, Nakamura R, Jackson PK, Frydman J, Andino R, Cell 2021 12 184 25 6037-6051.e14

Ethacridine inhibits SARS-CoV-2 by inactivating viral particles.

Li X, Lidsky PV, Xiao Y, Wu CT, Garcia-Knight M, Yang J, Nakayama T, Nayak JV, Jackson PK, Andino R, Shu X, PLoS Pathog 2021 09 17 9 e1009898

Myosin-Va is required for preciliary vesicle transportation to the mother centriole during ciliogenesis.

Wu CT, Chen HY, Tang TK Nat. Cell Biol. 2018 Feb 20 2 175-185

Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles.

Chen HY, Wu CT, Tang CC, Lin YN, Wang WJ, Tang TK Nat Commun 2017 Aug 8 1 247