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Defining the Role of ANKEF1 in Ciliary Function and Host Defense Against Influenza Virus Infection

Award Number: R01AI193023
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Defining the Role of ANKEF1 in Ciliary Function and Host Defense Against Influenza Virus Infection - Project Summary Most influenza cases resolve without complications, but some progress to life-threatening conditions like pneumonia, acute respiratory distress syndrome, or encephalitis. Genetic predispositions, such as inborn errors of immunity, are known factors that contribute to these severe outcomes, yet the underlying mechanisms in otherwise healthy individuals, particularly children, remain unclear. This proposal investigates the role of ANKEF1, a ciliary protein identified through a rare, homozygous loss-of-function mutation in a child who died of influenza-associated rhombencephalitis, a rare but severe complication. Our preliminary data show that ANKEF1 is essential for ciliary motility in airway epithelial cells, a process critical for effective mucociliary clearance. In mouse models, ANKEF1 deficiency leads to impaired antiviral defense, increased susceptibility to influenza infection, and higher morbidity and mortality. We hypothesize that ANKEF1 maintains the structural and functional integrity of the respiratory epithelium to support effective antiviral defense. In this proposal, we will combine novel mouse models, human iPSC-derived airway epithelial cultures, and targeted proteomics and transcriptomic approaches to define how ANKEF1 regulates ciliary function and host- pathogen interactions. Aim 1 will assess how ANKEF1 deficiency alters ciliary beat frequency, coordination, and motility in the airway epithelium, and will determine how these defects influence viral replication and immune responses ex vivo. Aim 2 will characterize disease progression in ANKEF1-deficient mice by measuring viral titers, immune responses, and tissue damage. Additionally, will use single-cell RNA sequencing to resolve cell- type–specific responses underlying increased disease severity. Aim 3 will define how ANKEF1 modulates ciliary functions and host defense by identifying key regulatory networks that mediate protection against influenza infection. This research will advance our understanding of the intersection between ciliary biology and antiviral immunity, with the potential to reveal new therapeutic targets for severe influenza and other cilia-related respiratory diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $868,915 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	6/18/2026	NEW	$868,915
														Subtotal = $868,915

Grand Total All Awards = $868,915

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Defining the Role of ANKEF1 in Ciliary Function and Host Defense Against Influenza Virus Infection

Award Number: R01AI193023

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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