|Institution||College of Medicine|
|Address||500 University Drive Hershey PA 17033|
Evan Pugh Professor of Pediatrics and Obstetrics & Gynecology
SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):
Obstetrics and Gynecology
GRADUATE PROGRAM AFFILIATIONS:
Cell and Molecular Biology, MD/PhD Degree Program
Ph.D., Temple University School of Medicine, 1980
Postdoctoral Training, Harvard Medical School, 1980-1982
Dr. Floros leads a research program focused on the regulation of expression and/or function of pulmonary surfactant proteins, SP-A, SP-B, SP-D, and their role in pulmonary disease. The specific hypothesis states that regulatory, functional, or structural differences among the surfactant protein genetic variants are altered under certain circumstances. These changes in turn determine or contribute to the disease or the health status of an individual. Therefore, study of such differences among surfactant protein variants may contribute to our better understanding of the observed individual variability in the susceptibility of pulmonary disease. Dr. Floros's current research activities include: a) studies of molecular mechanisms involved in the regulation of human SP-A and SP-B variants/genes in health and disease, b) studies of functional differences among the human SP-A variants/genes in the presence or absence of environmental insults, such as ozone exposure; c) studies of genetic associations of surfactant protein variants and pulmonary disease with emphasis on neonatal Respiratory Distress Syndrome (RDS).
Background: Pulmonary surfactant is a lipoprotein complex essential for normal lung function, and surfactant deficiency in the prematurely born infant can lead to Respiratory Distress Syndrome (RDS). SP-A, SP-B, SP-C, and SP-D are involved in important surfactant functions, such as the maintenance of alveolar integrity and/or the regulation of inflammatory processes and the local host defense of the lung. Therefore, functional or quantitative aberration of surfactant proteins may lead to surfactant dysfunction and/or to compromised host defenses in the lung. The surfactant proteins are regulated developmentally, hormonally, and in a tissue-specific manner. The human SP-A locus consists of two functional genes and one pseudogene, whereas all animal species (except primates) appear to have only one gene. Based on coding sequences, a number of variants have been identified and characterized for each functional human SP-A gene. In humans, SP-A levels have been shown to vary under certain circumstances. Low levels of SP-A mRNA have been associated with a specific SP-A genotype and the ratio of SP-A1 to total SP-A has been shown to vary as a function of age and disease. Also, differences among SP-A variants in response to glucocorticoids have been observed. This may, for example, explain the differential response observed with regards to lung maturity in prematurely born babies to mothers who received prenatal steroid therapy. Moreover, the SP-A variants differ among themselves at amino acids with potentially different sensitivities to oxidation following, for example, exposure to agents such as ozone. Differential oxidation of SP-A variants may result in SP-A dysfunction and this in turn may differentially contribute to pulmonary disease susceptibility. A number of variants have also been identified and characterized, albeit to a lesser extent, for SP-B as well as for SP-D. SP-A and SP-B variants have been shown to associate with pulmonary disease in subgroups of neonatal RDS and in groups with other pulmonary diseases. SP-A susceptibility or protective alleles and haplotypes have been identified for RDS. In summary, Dr. Floros' overall research interests are focused on the regulation and function of surfactant protein variants in health and disease. The hope is that findings from the model system of the surfactant protein variants will shed light on the genetic underpinnings with regards to individual variability to susceptibility of pulmonary disease, and/or to differential drug response.
Click the "See All" links for more information and interactive visualizations!
People who are also in this person's primary department.