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Ph.D. 1976
Northwestern University Medical School (Chicago, IL)
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Jacob
N. Finkelstein
Associate Director, Strong Children's Research Center
Primary Appointment:
Pediatrics
GEBS Cluster Affiliations:
MOCB - Molecular
Oncology and Cancer Biology
MTEM
- Molecular Toxicology and Environmental Medicine
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Research:
[short description] |
Contact Information:
E-Mail: finj@ehsct7.envmed.rochester.edu |
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 777
Rochester, New York 14642
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Medical Center [room]
Phone: (716) [tele]
Fax: (716) [number] |
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Research
Overview
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My laboratory is actively involved in investigating
the development and maintenance of differentiated functions
of the pulmonary alveolar epithelium and the role of specific
cell-cell interactions in controlling developmental processes.
Within this broad framework, our laboratory is proceeding with
a number of specific projects to more clearly define the cellular
and molecular control mechanisms which are critical to lung
development and repair in response to tissue and cell injury.
To address this broad question the laboratory has developed
a number of in vivo and in vitro models to permit detailed and
specific analysis of cell specific gene expression.
A major aspect of the work in the laboratory is focused on the
control of lung parenchymal cell proliferation during development
and especially during tissue repair after injury. The type II
cell plays an important role as the stem cell for renewal of
the alveolar epithelium both in the normal lung and especially
during lung injury resulting in type I cell epithelial death.
In addition, it may play a critical role in the regulation of
the functions of interstitial fibroblasts during lung growth
or pulmonary fibrosis such as cell proliferation or synthesis
and assembly of extracellular matrix components. Our current
working hypothesis is that many of these processes are regulated
through intercellular communication by the production of and
response to specific mediators or "growth factors" whose role
it is to modulate and program cellular functions. The overall
goal of this work is to identify the specific mediators produced
by the type II cell following injury and to identify the key
control mechanisms which are involved in these responses. Such
information would be valuable in determining how lung growth
and repair of epithelial damage are regulated during normal
and pathological circumstances.
The regeneration of the alveolar epithelium after severe tissue
injury, induced by systemic or inhaled agents, requires the
induction of controlled proliferation and differentiation of
the alveolar type II cell. We have identified a number of key
regulatory growth factors that function to induce epithelial
proliferation and differentiation that are actively synthesized
and secreted by inflammatory cells. We are currently in the
process of purifying these factors and cloning the specific
genes. We have also begun to characterize the receptors for
these substances on the epithelial cell surface and plan to
examine the role of these substances during normal lung growth.
Proliferation of pulmonary fibroblasts and enhanced production
of extracellular matrix components by these cells results in
tissue fibrosis and subsequent degradation of lung function.
Factors which may control the responses of fibroblasts in the
lung are not clearly defined. Inflammatory cells are known to
produce various cytokines/growth factors which can modulate
some aspects of fibroblast growth. The potential interactions
between the alveolar epithelium and interstitial fibroblasts
have not been investigated. We suggest that the type II cell
may act to control fibroblast function through the production
of specific growth factors. Further, the production of these
factors is altered by type II cell injury.
A third area of investigation addresses the role of epithelial
derived factors in the regulation of inflammatory cell recruitment
and activation. Although inflammation is a well known consequence
of inhaled toxicants, the source of the obligate chemotactic
or activating signals is poorly understood. Furthermore, the
regulation and source of production of anti-inflammatory cytokines
remains to be elucidated. Using, well characterized models of
inflammation we have identified changes in proinflammatory gene
abundance in epithelial cells and are examining the transcriptional
and post-transcriptional regulation of these genes in pulmonary
epithelial and resident inflammatory cells.
Taken together these data suggest the existence of a complex
intercellular communication network which plays a key role in
determining the overall tissue response to exogenous stresses.
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Recent Publications
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Johnston CJ, Piedboeuf B, Baggs R, Rubin P, Finkelstein JN.
Differences in correlation of mRNA gene expression in mice
sensitive and resistant to radiation-induced pulmonary fibrosis.
Rad Res 142:193-199, 1995.
142:193-199, 1995.Tox and Applied Pharm. 140(1):154-163,
1996.
O'Reilly MA, Staversky RJ, Flanders KC, Johnston CJ, Finkelstein
JN. Temporal changes in expression of TGF- isoforms in mouse
lung exposed to oxygen. Am. J. Physiol. (Lung Cell.-Mol.
Physiol.) 272:L60-L67, 1997.
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