Analysis of the impact of natural aging and premature aging on lung health and function.
Analysis of lung regeneration using a novel mouse model developed in my lab in which mild, moderate or severe lung injury can be induced in a precisely controlled manner.
Analysis of the impact of stem cell and pharmaceutical therapies on the inevitable deterioration due to aging and premature aging of the lung.
Functional characterization of stem cells isolated from pediatric patients suffering severe cardiopulmonary injury and/or failure.
LUNG HEALTH & FUNCTION RESEARCH OVERVIEW
My lab investigates the impact of aging and, in the case of younger individuals, premature aging, on lung health and function. We are particularly interested in how aging affects the ability of lung progenitor cells to resist disease and function in injury repair. We are also interested in determining how these cells interact with other types of cells, including stem cells, that exist within the lung or come into the lung from the circulatory system, and how this interaction can stimulate or impede the aging process and the repair of lung injury. In all these studies we analyze cellular pathways related to oxidative stress, inflammation and changes in the cell cycle.
We have made several discoveries of key markers for premature aging that show up in the lungs of younger individuals that carry specific genetic mutations, which we hope will lead to the design of intervention therapies, including the use of specialized stem cells that modify the lung environment. Recently my lab developed an in vivo model for the study of lung injury. This model can be “fine-tuned” so that lung injury can be induced to mild, moderate or severe levels.
With a clinical collaborator, Kim Bui,MD, we have also begun to examine a unique population of stem cells isolated from pediatric patients that survive severe cardiopulmonary injury. We hope to determine if these cells can be used therapeutically in the treatment of pediatric heart and lung failure.
RESEARCH FOCUS
Analysis of the functional impact of natural aging and premature aging due to chromosomal telomere shortening.
These studies have provided the following novel information for the field:
Telomerase is upregulated in lung epithelial cells during regeneration following injury
Telomerase dysfunction and telomere shortening inhibit lung injury repair by inducing epithelial cell growth arrest, rather than proliferation, in response to regenerative stimuli
Lung epithelial cells from telomerase/telomere dysfunctional animals exhibit significant and chronic DNA damage even in absence of injury
Telomere shortening and subsequent chromosomal destabilization have a direct impact on mitochondrial integrity, which in turn induces epithelial cell senescence
The increase in arrested, damaged and senescent epithelial cells in aging lung are conducive to the development of fibrosis
Naturally aged lung and lung prematurely aged due to telomerase/telomere dysfunction share a number of functional characteristics and changes in key signaling pathways, particularly those that regulate the cell cycle and the response to oxidative stress
Analysis of the impact of stem cell and pharmaceutical therapies on the inevitable deterioration due to lung aging.
These studies make use of the knowledge acquired using our naturally and prematurely aged models. We are hoping to design therapeutic approaches to the buildup of senescent cells and the increased levels of inflammation that occur as the lung ages. We are currently analyzing the impact of systemic versus lung-specific administration of mesenchymal stem cells, as well as certain drugs, on the baseline integrity of the lung. These treatments are being assessed for their ability to influence lung injury response, the lung inflammatory environment and pulmonary function.
Analysis of lung regeneration using a novel model developed in my lab in which mild, moderate or severe lung injury can be induced in a precisely controlled manner.
These studies have shown us that a myriad of cell types and factors respond to distal lung epithelial cell injury, and have thus provided us with a number of targets, including pulmonary and circulating mesenchymal and immune cells, that could be modified in order to stimulate robust lung regeneration.
Functional characterization of stem cells isolated from pediatric patients suffering severe cardiopulmonary injury/failure.
With my clinical collaborator, Dr. Kim Bui, we have begun to examine a unique population of stem cells isolated from pediatric patients that survive severe cardiopulmonary injury. Dr. Bui has shown that these cells are a rare, non-tumorigenic stem cell that can be cultured from the peripheral blood of patients who have suffered such significant lung and/or heart injury that they require extra-corporal membrane oxygenation (ECMO) therapy. My lab has shown that these cells are significantly more attracted to sites of lung injury than normal, bone marrow-derived stem cells. We are currently working to functionally characterize these cells in the context of in vivo lung injury order to determine if the ECMO patient-derived cells can be used therapeutically in the treatment of pediatric heart and lung failure.
KEY FINDINGS
Telomerase is upregulated in lung epithelial cells during regeneration following injury and telomerase dysfunction and telomere shortening inhibit lung injury repair by inducing epithelial cell growth arrest, rather than proliferation, in response to regenerative stimuli.
Lung epithelial cells from telomerase/telomere dysfunctional animals exhibit significant and chronic chromosomal and mitochondrial DNA damage even in absence of injury.
Naturally aged lung and lung prematurely aged due to telomerase/telomere dysfunction share a number of functional characteristics and changes in key signaling pathways, particularly those that regulate the cell cycle and the response to oxidative stress.
CURRENT FUNDING
NIH/NHLBI R01 Alveolar epithelial cells: development and repair (PI: Driscoll) This grant supports ongoing work on the impact of telomere shortening, natural aging and premature aging on lung injury and repair.
CIRM Bridges to Stem Cell Award (Driscoll Co-PI with PI Eversole-Cire) This grant supports the training of Pasadena City College Biotechnology students in stem cell biology and hands-on training in stem cell laboratory techniques in labs located at THE UNIVERSITY OF SOUTHERN CALIFORNIA, Children’s Hospital Los Angeles and CalTech.
CIRM Stem Cell Training Grant (Driscoll Co-PI with Co-PI Warburton) This grant supports training basic research post-doctoral fellows and clinical research fellows at of Children’s Hospital Los Angeles, THE UNIVERSITY OF SOUTHERN CALIFORNIA and CalTech in stem cell biology and hands-on training in labs doing stem cell laboratory research.
AWARDS
Doyle-Hilligoss Award, University of San Diego
The Shaffer Lecture, University of San Diego
Partnership Award, Pasadena City College
CONTACT US
Barbara Driscoll Lab The Saban Research Institute
4661 Sunset Boulevard
MS# 35
Los Angeles, CA 90027
Email: Barbara Driscoll, PhD
Office: 323-361-4687
Fax: 323-361-3613
