# Bcl-2 dependent fibroblast resistance to apoptosis occurs through persistent IL-6 signaling

> **NIH NIH K08** · NATIONAL JEWISH HEALTH · 2024 · $156,816

## Abstract

PROJECT SUMMARY
 This proposal describes a five-year project through which Dr. Joseph Cooley will develop the skills and
knowledge necessary to transition into an independent basic and translational physician-scientist. He will receive
mentorship from a primary mentor, several advisors and collaborators from National Jewish Health and the
University of Colorado. His long-term career goal is to help patients with fibrotic lung diseases by uncovering
mechanisms of progressive pulmonary fibrosis (PPF) and developing therapeutic strategies to halt or reverse
fibrosis. This proposal explores how interleukin-6 (IL-6) promotes apoptosis resistance in fibroblasts by
increasing expression of the anti-apoptotic protein BCL-2, and how this IL-6-BCL-2 axis can be targeted
therapeutically. It is directly relevant to the NHLBI given its applicability to all progressive fibrosing interstitial lung
diseases (ILDs). Candidate: Joseph Cooley, DO is board certified in Internal, Pulmonary, and Critical Care
Medicine. He is an Instructor at National Jewish Health in Denver, CO who clinically specializes in ILD and
performs rigorous basic and translational scientific investigations related to pulmonary fibrosis as a physician-
scientist. Training: Dr. Cooley has created an extensive career development plan that builds on his prior
mentored research during medical school, residency, and fellowship training. His multi-faceted career
development plan utilizes formal classwork, conferences, seminars, workshops, small and large group
collaborative meetings, and on-on-one training to develop and expand his skills and knowledge of 1) biologic
concepts related to mechanisms of cell death, biostatistics, genetics and genomics, and lung injury, repair and
fibrosis, 2) laboratory techniques, 3) scientific writing, 4) rigorous experimental design, 5) data interpretation, 6)
oral presentation, and 7) leadership, mentorship and laboratory management. Mentor/Environment: Dr.
Cooley’s primary mentor is Dr. Elizabeth Redente, PhD whose laboratory has a history of producing high-impact
research regarding fibroblasts behavior during lung injury, repair and fibrosis. Dr. Cooley has assembled a team
of mentors and collaborators that are experts in pertinent aspects of the project including advanced genomic
analysis techniques (Dr. Gerber), cutting edge gene transfer techniques using viral vectors (Dr. Bridges),
genetics and genomics of pulmonary fibrosis (Dr. Schwartz), and IL-6 signaling across diverse disease states
(Dr. Rincon). All proposed activities will be performed at National Jewish Health, a highly collaborative top-ranked
research institution. Research Project: The primary objective of this proposal is to determine if fibroblast BCL-
2 dependent apoptosis resistance is driven by sustained IL-6 signaling in PPF, and if this IL-6-BCL-2 axis can
be targeted therapeutically to treat PPF. We will use in vitro cell culture and precision cut lung slices from humans
and mice, and in vi...

## Key facts

- **NIH application ID:** 10985897
- **Project number:** 1K08HL171850-01A1
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Joseph Charles Cooley
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $156,816
- **Award type:** 1
- **Project period:** 2024-07-15 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985897

## Citation

> US National Institutes of Health, RePORTER application 10985897, Bcl-2 dependent fibroblast resistance to apoptosis occurs through persistent IL-6 signaling (1K08HL171850-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10985897. Licensed CC0.

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