Basic and Translational Research
Penn's Division of Thoracic Surgery maintains four separate but
interrelated scientific research laboratories. The goals of each of
these laboratories is both to advance basic medical knowledge
in areas relevant to thoracic surgery and to bring these advances to
the clinic as soon as feasible. Our presence within one of the
world's great research universities allows us to collaborate with
basic scientists of the highest caliber in our work.
The Thoracic Oncology Research Laboratory
Co-directed by Larry Kaiser, MD and Steve Albelda, MD of Pulmonary
Medicine, with important contributions by Daniel Sterman, MD and
Anil Vachani, MD of Pulmonary Medicine, this laboratory maintains funding
from the NIH/NCI and is focused upon a number of experimental
treatments for lung cancer and mesothelioma based upon recent
advances in molecular biology, immunotherapy, and gene therapy.
After promising work in pre-clinical animal models, this group
carried out three Phase I trials for mesothelioma using an
adenovirus expressing a Herpes Simplex Thymidine Kinase gene.
Subsequent basic and clinical work has focused upon immunogene
therapy with an adenovirus vector containing the interferon-beta
gene. It is hoped that this work will establish some combination of
surgical debulking and gene therapy to be an effective treatment for
pleural malignancies in the future. Another avenue of research ongoing
in this laboratory is an effort to develop early means of detecting lung
cancer using genomic and proteomic approaches.
The Respiratory Muscle Research Laboratory
Co-directed by Joseph Shrager, MD, and Sanford Levine, MD, this laboratory
is focused upon the function and dysfunction of the diaphragm and
other muscles of respiration in health and disease. This laboratory has
been funded by the American Association for Thoracic Surgery, The
Veterans Affairs Merit Review system, and the NIH/NHLBI. It has
published groundbreaking work establishing the cellular and molecular
adaptations that occur in the diaphragm in emphysema and after lung
volume reduction surgery.
A major current focus is determination of the
mechanisms of the apparent negative impact of mechanical ventilation
upon diaphragmatic muscle fibers. This problem is felt to be partially
responsible for failure to wean from the ventilator, and it is hoped
that delineation of the mechanisms will lead to a clinical trial of drugs
that block the involved pathways.
The Penn Presbyterian Thoracic Research Laboratory
Directed by Joseph Friedberg, MD, this laboratory is focused
upon several areas of interest including both oncologic and nononcologic
topics. The primary oncology focus is on innovative
treatments for lung cancer and mesothelioma that are synergistic
with photodynamic therapy.
This lab is also studying a variety
of techniques for immunotherapy utilizing autologous tumor
extracts to create vaccines. This lab's non-oncologic research
includes a number of projects: “artificial” lung technology, photodynamic
therapy as an antifungal treatment, a non-invasive technique for identifying
and sealing airleaks that occur during pulmonary surgery, and altering the
optical properties of tissues to permit entire organ photodynamic therapy.
The Emphysema Research Laboratory
Directed by Joel Cooper, MD, this laboratory is focused upon the pathophysiology
of development of new therapies for emphysema. A canine
model of emphysema is being utilized to develop a helium-MRI based,
non-invasive means of detecting early emphysema and monitoring its
progress. This canine model, as well as explanted emphysema lungs from
transplant recipients, is being used to develop an airway bypass procedure
in which passages are created between segmental bronchi and adjacent
destroyed parenchyma.
Clinical trials of this technique are ongoing and it is
hoped that this might provide a less invasive means of “volume reduction”
for emphysema patients. Explanted emphysema lungs are also being
evaluated by molecular and cell biologic techniques to assess the role of
inflammation in producing pulmonary destruction in this disease.
Finally, optoplethysmography, a technique of measuring detailed chest
wall mechanics by placement of infrared markers over the chest wall, is
being used to study the impact of LVRS, exercise rehabilitation, and
other interventions upon respiratory mechanics.
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