Dr. Probal Banerjee, Associate Professor of Biology at The Graduate Center, is affiliated with the Center for Developmental Neuroscience and Developmental Disabilities at the College of Staten Island. His research team at the College of Staten Island is divided into two groups to study the role of the serotonin 1A receptor (5-HT1A-R) in the survival and maturation of brain neurons during development, and the gene structure and expression of ATPase II, which is a candidate for an enzyme, aminophospholipid translocase, that translocates the cell membrane lipid molecule phosphatidylserine to the inner leaflet of the plasma membrane.
Trophic Role of The Serotonin 1A Receptor in Brain Development
Earlier studies performed by Dr. Banerjee's team have shown that a signaling pathway initiated by the binding of the neurotransmitter serotonin to the 5-HT1A-R (stimulation) causes inhibition of programmed cell death (apoptosis) in stressed neuronal cells by attenuating the activity of a pro-apoptotic enzyme caspase-3. Previous studies have also shown that stimulation of the 5-HT1A-R also causes increased division of undifferentiated neuronal cells. Based on such information it has been postulated that during brain development, the 5-HT1A-R plays a dual role by promoting division of preneuronal cells during early stages and then protecting the maturing neurons during the later stages of brain development. Other studies have shown that the absence of the 5-HT1A-R during brain development causes an increased anxiety syndrome in knockout mice. Anxiety and depression are critically regulated by neuronal connections between the hippocampus and amygdala, which generate the strong feelings, and the forebrain, which helps analyze the feelings and generates commands for action. Dr. Banerjee's team is studying the effect of 5-HT1A-R stimulation on the formation of neuronal connections by antibody staining of mouse brain sections at various stages of brain development. This research, which is being conducted with colleagues at New York University, is supported by the National Institute of Mental Health (NIH)
Regulation and Role of ATPase II in Neuronal Cells
Phosphatidylserine (PS) is an inner plasma membrane lipid in normal cells, but apoptotic cells display PS in the outer leaflet of their plasma membrane. Phagocytic cells such as macrophages and microglia recognize these apoptotic cells by the presence of surface PS molecules. This recognition causes binding of PS-receptors residing on the phagocytic cells to the surface PS molecules resulting in phogocytosis of the apoptotic cells. In the absence of phagocytosis, these apoptotic cells would eventually burst open and spill their toxic contents on the neighboring tissue. Such apoptotic cells are typically generated in the brain during chemotherapy-mediated clearance of brain tumor cells. Previous studies performed by Dr. Banerjee's team has shown that apoptosis is accompanied by an inhibition of the enzyme aminophospholipid translocase (APTL) that catalyzes inner leaflet localization of PS. Inhibition of APTL causes the inner-leaflet-localized PS molecules to flip-flop out to the surface of the cells. A known protein, a P-type ATPase (ATPase II), has very similar properties to that of the enzyme APTL and is therefore postulated to be an APTL. Overexpression of ATPase II cDNA in neuronal HN2 cells caused increased PS internalization and expression of antisense ATPase II cDNA in the same cells caused PS externalization, thus strengthening the hypothesis "ATPase II is an APTL". Expression levels of ATPase II show strong tissue-specificity, with the brain neurons expressing high levels of this enzyme. To understand the role and tissue-specific expression of ATPase II, its gene structure and the mechanism of expression are being studied in neuronal cell lines. The final objective of this project is to manipulate the ATPase II gene to regulate phagocytosis and clearance of brain tumor cells without the use of chemotherapy. The research is supported by the National Cancer Institute (NIH).
http://www.csi.cuny.edu/divsci/banerj.htm