Sunday, February 15, 2026 2/15/2026

Burkholderia-mediated defective killing mechanisms in macrophages from cystic fibrosis (CF) patients

Award Number: K08AI108792
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/15/2015
PERIOD OF PERFORMANCE END DATE: 12/31/2020

Group Awards By:

View Award Description

Burkholderia-mediated defective killing mechanisms in macrophages from cystic fibrosis (CF) patients - ¿ DESCRIPTION (provided by applicant): As a pediatric pulmonologist, my long-term career goal is to become a physician-scientist who is an expert in the immunologic control of microbial infections in cystic fibrosis (CF). My short-term educational and research plans for this K08 award are focused on gaining scientific independence through a detailed understanding of the macrophage control of Burkholderia infections in CF. My resident and fellowship research training has allowed me to discover deficiencies in macrophage autophagy in both murine and human CF models that play a key role in Burkholderia virulence in CF. Newly acquired data suggest that Burkholderia species affect the CF macrophage oxidative burst, but it is unknown how this ties in with autophagy signaling in CF. The pursuit of these potentially intertwined pathways will generate the necessary fundamental knowledge for developing R01 grant proposals with the ultimate goal of future clinical trials of novel host-directed therapies for improving treatment of acute and chronic infections in CF. The K08 mechanism will allow me to focus at least 75% of my efforts on developing an independent translational research career. My career development plan will utilize a structured approach with specific objectives to allow me to transition to an independent research career. My training objectives include: 1) Gaining expertise in the study of autophagy and NADPH oxidase-mediated pathways relating to pathogen clearance; 2) Training in the manipulation of macrophage signaling responses to pathogens; and 3) Enhancing translational research design skills for the development of pre-clinical and clinical trials. I will achieve these objectives through hands-on scientific training ia my research mentors and mentoring advisory committee, relevant coursework, participation in a Master's in Public Health for Professionals program, and scientific seminars. Through this approach I will both broadly and specifically enhance my research skills in order to fully develop my independent research lab and research program to facilitate my achievement of independent funding by the completion of a K08 award. The research plan utilizes a human macrophage model of Burkholderia infection in CF to study evasion of host immune responses. My preliminary data suggests that Burkholderia are able to suppress an already dysfunctional oxidative burst in CF to avoid host killing. This also leads to a downstream reduction in autophagosome formation, further decreasing pathogen killing. We hypothesize that Burkholderia survival in CF is predicated upon both the disruption of the NADPH oxidase for generation of reactive oxygen species and the deficient assembly of autophagosomes for targeted intracellular bacterial killing. We will analyze both the assembly and generation of the oxidative burst, as well as signaling interactions between ROS and autophagy initiation. The anticipated outcome of this work is that it will advance our understanding of potential antibiotic- independent targets for drug delivery and/or discovery for antibiotic-resistant Burkholderia infections in CF. The significance of these studies is reflected in our current lack of a gold standard treatment for these deadly infections in CF. The environments of the Center for Microbial Pathogenesis at the Research Institute at Nationwide Children's Hospital (RINCH) and the Center for Microbial Interface Biology at The Ohio State University are outstanding and ideally suited for the achievement of this research plan and training objectives. I will utilize a skilled mentoring team to provide comprehensive research guidance and training. Dr. Larry Schlesinger is a world leader in macrophage biology and macrophage-pathogen interactions with a long and distinguished training record. His leadership is coupled with co-mentor Dr. Amal Amer's expertise in Burkholderia pathogenesis, including novel mechanisms of autophagy deficiency. Additionally, my mentor advisory committee features further expertise in clinical, translational, and basic CF research in addition to CF-specific bacterial pathogenesis. I also have the unique benefit of working in two state-of-the-art facilities and receiving support from experts in both clinical and basic science research cores. Institutional support from the RINCH will allow me to continue to devote 75% of my time towards the proposed training and research. Through this interdisciplinary mentoring approach I will greatly enhance my scientific progression and successful competition for independent R01 level funding during the course of this K08 award.


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: 2021 ( Subtotal = $0 )
2021	2019	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	5	9/16/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $176,504 )
2019	2019	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	5	12/27/2018	NON-COMPETING CONTINUATION	$176,504
														Subtotal = $176,504

Issue Date FY: 2018 ( Subtotal = $176,504 )
2018	2018	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	4	12/29/2017	NON-COMPETING CONTINUATION	$176,504
														Subtotal = $176,504

Issue Date FY: 2017 ( Subtotal = $176,504 )
2017	2017	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	3	12/14/2016	NON-COMPETING CONTINUATION	$176,504
														Subtotal = $176,504

Issue Date FY: 2016 ( Subtotal = $151,200 )
2016	2016	Research Institute at Nationwide`s Children`s Hospital	700 CHILDREN`S DRIVE	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	2	11/27/2015	NON-COMPETING CONTINUATION	$151,200
														Subtotal = $151,200

Issue Date FY: 2015 ( Subtotal = $150,912 )
2015	2015	Research Institute at Nationwide`s Children`s Hospital	700 CHILDREN`S DRIVE	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	1	1/14/2015	NEW	$150,912
														Subtotal = $150,912

Grand Total All Awards = $831,624

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Burkholderia-mediated defective killing mechanisms in macrophages from cystic fibrosis (CF) patients

Award Number: K08AI108792

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/15/2015

PERIOD OF PERFORMANCE END DATE: 12/31/2020

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer