Sever-Chroneos, Zvjezdana, Ph.D.

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Contact: zvjezdana.sever-chroneos@uthct.edu

Education:
B.S. 1989, Zagreb, Croatia
Ph.D. 1999, Cincinnati, OH

Research Interest:
The pulmonary surfactant and innate lung defense.
Lung infectious diseases.

Current Projects:

1. Interaction of Surfactant protein A with Staphylococcus aureus.
2. The role of Surfactant protein A in the cell cycle - dependent invasion of lung monocytes by Mycobacterium tuberculosis.

Lay Summary:
Staphylococcus aureus is a gram positive human pathogen and a major etiologic agent of community and hospital acquired infections causing a wide variety of clinical syndromes. The attachment and spread of this organism is largely mediated by a family of extracellular adhesin proteins. Virulence and pathogenesis of Staphylococcus aureus are on the other hand mediated by toxins and molecules carrying superantigen properties. Since Staphylococcus aureus is one of the most adept organisms with antibiotic resistance, there is an alarming urgency for understanding its virulence and reducing its spread.
Surfactant protein A is the most abundant protein component of the surfactant mixture lining the alveolar spaces of the lung. SP-A is a first line of innate defense and coordinates the lung response to pathogen insult. SP-A is a member of the collectin glycoprotein family capable of interacting with a wide range of bacteria and viruses known to colonize lung compartments. SP-A directs phagocytosis of pathogens through the interaction with cell surface receptors largely expressed by monocytes and macrophages in the lung.

Research Overview:
The mechanism of Surfactant protein A interaction with Staphylococcus aureus is critical in understanding the strategic role of lung surfactant in the host defense. Our experiments indicate that SP-A is an opsonin for S. aureus in vitro. Given that SP-A is known to be involved in clearing of bacteria from respiratory spaces, we aim to investigate the role of SP-A binding to S. aureus in vitro and in vivo. We have discovered that SP-A interacts with several S. aureus extracellular proteins some of which are adhesins. The current project will characterize the biochemical nature of bacterial protein interaction with SP-A. These experiments aim to understand the role of SP-A in staphylococcal attachment to a variety of eukaryotic cell types. The study will help open new avenues in understanding the surfactant role in pathogen eradication in the lung.

Selected Papers and Abstracts:

• Lan Z, Sever-Chroneos Z, Strobeck MW, Park CH, Baskaran R, Edelmann W, Leone G, Knudsen ES. DNA damage invokes mismatch repair-dependent cyclin D1 attenuation and retinoblastoma signaling pathways to inhibit CDK2. J Biol Chem. 2002 Mar;277(10):8372-81. Epub 2001 Nov 28.
• Sever-Chroneos Z, Angus SP, Fribourg AF, Wan H, Todorov I, Knudsen KE, Knudsen ES. Retinoblastoma tumor suppressor protein signals through inhibition of cyclin-dependent kinase 2 activity to disrupt PCNA function in S phase. Mol Cell Biol. 2001 Jun;21(12):4032-45.
• Knudsen KE, Booth D, Naderi S, Sever-Chroneos Z, Fribourg AF, Hunton IC, Feramisco JR, Wang JY, Knudsen ES. RB-dependent S-phase response to DNA damage. Mol Cell Biol. 2000 Oct;20(20):7751-63.
• Sever-Chroneos Z, Bachurski CJ, Yan C, Whitsett JA. Regulation of mouse SP-B gene promoter by AP-1 family members. Am J Physiol. 1999 Jul;277(1 Pt 1):L79-88.
• Yan C, Sever Z, Whitsett JA. Upstream enhancer activity in the human surfactant protein B gene is mediated by thyroid transcription factor 1. J Biol Chem. 1995 Oct 20;270(42):24852-7.
• Yan C, Ghaffari M, Whitsett JA, Zeng X, Sever Z, Lin S. Retinoic acid-receptor activation of SP-B gene transcription in respiratory epithelial cells. Am J Physiol. 1998 Aug;275(2 Pt 1):L239-46.