Dr. Beers holds a joint appointment in the Pulmonary, Allergy,
and Critical Care Division and the Institute for Environmental
Medicine.
Characterization of surfactant protein trafficking (synthesis,
secretion, and uptake) and its regulation in lung epithelial
cells; post-translational modification of surfactant proteins;
developmental expression of surfactant proteins, and the
role of surfactant components in host defense and modulation
of the inflammatory response.
The pulmonary epithelium synthesizes and secretes a surface-active
film of biochemically heterogeneous lipoprotein mixture
(lung surfactant) that reduces surface tension at air-liquid
interfaces and allows for maintenance of alveolar stability
at low lung volumes. In addition several protein components
of the surfactant system are now recognized as part of an
emerging family of proteins important for innate host defense
and modulation of inflammation, the collectins. My laboratory
is engaged in the investigation of the life-cycle of the
surfactant proteins with studies directed at understanding
their synthesis, intracellular trafficking, and secretion
into the alveolar space. Current projects include the cellular
metabolism of surfactant protein C with emphasis on the
intracellular trafficking of SP-C and the role of SP-C in
the development of conformational lung disease, expression
and synthetic processing of surfactant protein C in human
fetal lung, regulation of SP-A and SP-C synthesis in congenital
SP-B deficiency, and characterization of the surfactant
expression and function in asthma, the role of surfactant
in local host defense and pathogenesis of Pneumocystis carinii
lung infection. Results from these studies will have direct
applicability toward the understanding of the role of altered
surfactant metabolism and function in the pathogenesis of
both adult and neonatal pulmonary disease including ARDS,
neonatal RDS, surfactant protein deficiencies, and alveolar
proteinosis.
Mulugeta S, Maguire JA, Russo SJ, Kotorashvili A, Newitt
J, and MF Beers. Misfolded BRICHOS SP-C mutant proteins
induce apoptosis via caspase 4 and cytochrome c related
mechanisms. American Journal of Physiology 293: L720-L729
2007.
Jain D, Atochina-Vasserman EN, Kadire H, Tomer Y, Inch A,
Gow A, Scott P and MF Beers. SP-D deficient mice are resistant
to hyperoxia. Am J Physiol Lung Cell Mol Physiol 292: L861-871
2007.
Beers MF and S. Mulugeta. Surfactant Protein C biosynthesis
and its emerging role in conformational lung disease. Annual
Review Physiology 67: 663-696 2005.
Mulugeta S, Nguyen V, Russo SJ, Muniswamy M and Beers MF.
A ProSP-C BRICHOS Domain Mutation Causes ER Stress, Proteasome
Dysfunction, and Caspase 3 Activation. Am J Resp Cell Mol
Biol. 32: 521-530 2005.
Stevens PA, Pettenazzo A, Baritussio A, Mulugeta S, Brasch
F, Ochs M, Russo SJ, Morrison L, and Beers MF. Non-Specific
Interstitial Pneumonitis, Alveolar Proteinosis, and Abnormal
Proprotein Trafficking in a Patient With a Novel Spontaneous
Mutation in Surfactant Protein C Gene. Pediatric Research
57: 89-98 2005.
Wang W-J, Mulugeta S, Russo SJ, and Beers MF. Deletion Of
Exon 4 From Human Surfactant Protein C Results In Aggresome
Formation and Generation of a Dominant Negative J Cell Science
116 (4) 683-692 2003.
Wang W-J, Russo SJ, Mulugeta S, and Beers MF. Biosynthesis
of surfactant protein C: Sorting of SP-C proprotein involves
oligomeric association via a signal anchor domain. J Biol
Chem 277: 19929-19937 2002.
Haczku, A, Atochina EN, Tomer Y, Chen H, Scanlon ST, Russo,
SR, Xu J, Panettieri RA, Jr, and Beers MF. Surfactant protein
dysregulation is associated with Aspergillus fumigatus induced
allergic inflammation and airway hyperresponsiveness. Am.
J. Resp. Cell. Mol. Biol. 25: 45-50, 2001.
Atochina EN, Beck JM, Scanlon ST, Preston AM, Beers MF.
Pneumocystis carinii pneumonia induces alteration in expression
and distribution of lung collectins SP-A and SP-D. J Lab
Clin Med 137: 429-439, 2001.
Kabore AF, Wang W-J, Russo SJ, Beers MF. Biosynthesis of
surfactant protein C: Characterization of aggresome formation
By EGFP chimeras containing propeptide mutants lacking conserved
cysteine residues. J. Cell Science 114 (2): 293-302, 2001.
Beers MF, Atochina EN, Scanlon ST, Preston AM, Beck JM.
Pneumocystis carinii pneumonia induces alterations in component
expression and biophysical properties of pulmonary surfactant.
Am J. Physiol. Lung Cell Mol Physiol. 278: L599-L609, 2000.
