INSTITUTION AND LOCATION

DEGREE

YEAR(s)

FIELD OF STUDY

University of Madras, India

Ph.D.

1972

Biology

2000-2007

Research Assistant Professor, Center of Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA

1997-1999

Research Associate, Center of Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA

1994-1996

Assistant Research Professor, Department of Ophthalmology, University of California, Los Angeles, CA

1993-1994

Assistant Research Professor, Department of Medicine-Division of Cardiology,  University of  California, Los Angeles, CA

1989-1993

Assistant Research Professor, Department of Neurology, University of California, Los Angeles, CA

1983-1988

Postdoctoral Researcher, Department of Biological Chemistry, University of California, Los Angeles, CA

1972-1982

Assistant Professor in Biology, University of Madras, Tamilnadu, India

2001-2005

Principal Investigator, National Institute of Dental Research "Lectin-like properties of Amelogenin"

2000-2001

Co-Investigator, (Alan Fincham, PI) National Institute of Dental Research "Lectin-like properties of Amelogenin"

1999-2000

Molecular mimicry of ligand interacting with Amelogenins, MFWA-Research Fund, University of Southern California

1994-1996

Co-Investigator, (Bartly J. Mondino, PI) National Institute of Health, Immune responses to Staphylococcal endophthalmitis"

1988-1989

Recipient of Biomedical Research Grant, University of California, Los Angeles

Provisional Patent application : USC File No. 3067- Amelogenin Trityrosyl Motif Peptide an Agent, Probe and Tool for Regulation of Assembly and Functions of Cytokeratins in Normal and Pathological Conditions.

Research Project # 1. The Enamel Protein Amelogenin Binds to a specific Sugar N-acetyl Glucosamine

Amelogenin is a major protein of the enamel. Amelogenins are secreted by ameloblasts at the dentine-enamel junction. We tested the hypothesis that the amelogenins interact with enamel matrix glycoproteins by a series of experiments. Our results showed that amelogenins bind specifically to N-acetyl glucosamine (GlcNAc) but not to glucosamine or glucose or any other sugar.  GlcNAc and its oligosaccharides as well as glycoproteins containing GlcNAc bound to Amelogenins. We further identified the specific domain in the amelogenins that recognizes GlcNAc. Our experiments revealed that GlcNAc binding domain is located at the tyrosine rich N-terminal domain of Amelogenins. The sequence that binds to GlcNAc is a 13-residue polypeptide containing three tyrosine’s, called  Amelogenin trityrosyl motif peptide or ATMP. The Amelogenins failed to bind to GlcNAc if the tryosyl residues are substituted with phenylalanine or when the third proline in the peptide sequence is replaced by threonine. Significantly this later modification mimics a point mutation identified in a case of human X-linked enamel defect called amelogenesis imperfecta.  Thus our findings have potential significance in understanding the biological function of amelogenins. The findings of the project has been published in J. Biol. Chemistry 274:2464-2471 (1999)

Research Project # 2. The Enamel Protein Amelogenin Binds to the GlcNAc-mimicking peptide motif of Cytokeratins.

In this project, the hypothesis that amelogenins may interact with the peptides that mimic GlcNAc is tested. GlcNAc-mimicking peptide but not its variants with single amino acid substitution at serine, tyrosine, or phenylalanine residues. The binding affinity of this peptide to amelogenins was confirmed by a series of experiments. The GlcNAc mimicking peptide failed to bind to the amelogenin trityrosyl motif peptide when the tyrosyl residues were substituted with phenylalanine or when the third proline is replaced with threonine as in some cases of human X-linked amelogenesis imperfecta. This study documents that molecular mimicry may play a role in stability and organization of amelogenin during amelogenesis. The details of this investigation were published in J. Biol. Chemistry 275:39654-39661 (2000).

Research Project # 3. The Cytokeratin 14 acts as a chaperon during secretion of amelogenin.

The binding affinity of CK14 and amelogenin was confirmed by a series of experiments. Blocking amelogenins with GlcNAc, GlcNAc-mimicking peptide or CK14 with ATMP abrogates the CK14-amelogenin interaction. CK14 failed to bind to ATMP when the third proline was substituted with threonine, as in some cases of human X-linked amelogenesis imperfecta or when tyrosyl residues were substituted with phenylalanine. Confocal microscopy of the developing tooth revealed co-assembly of CK14/amelogenin in the perinuclear region of ameloblasts on day 0, migration of the co-assembled CK14/amelogenin to the apical region of the ameloblasts from day 1, reaching a peak on days 3-5, and a collapse of the co-assembly. Autoradiographic studies corroborated the dissociation of the co-assembly at the ameloblast Tome's Process suggesting that CK14 is a chaperon for nascent amelogenin polypeptide during amelogenesis. The details of this investigation were published in J. Biol. Chemistry 276: 36586-36597 (2001).