The Faculty

Here are brief sketches and current research interests of the faculty of the M.S. Program in Biology (concentration in Oral Biology).

Identification of Periodontal Pathogens

Robert J. Boylan
Associate Professor of Basic Sciences (Microbiology)
_______________________________________________________________________________________________

1963 B.S.      University of Scranton
1967 M.S.     Duquesne University
1970 Ph.D.    University of Maryland
1970-73        Postdoc University of Rochester School of Medicine and Dentistry
1973-            New York University College of Dentistry, Dept. of  Basic Science and Craniofacial Biology
_______________________________________________________________________________________________

 Our laboratory is developing methods to rapidly identify periodontal pathogens. We are using DNA probes that specifically identify species, and even subspecies, of the anaerobic, gram-negative rods found in the plaque of people with periodontal disease in order to get a better understanding of these bacteria and the virulence factors they produce.
 

Relevant Publications:

Kaplan, B.A., Boylan, R.J., Goldstein, G. Effectiveness of professional strength lysol as a disinfectant for irreversible hydrocolloid. J. Prosth. Dent., 71:603-605, 1994.

Wong, W.S., Rosenberg, R.J., Boylan, R.J., Schulman, A. A comparison of the apical seals achieved using retrograde amalgam fillings and the ND:YAG laser. J. Endodont., 20:595-597, 1994.

Ciuffreda, L.Jr., Boylan, R.J., Scherer, W., Palat, M., Bacchi, A. An in vivo comparison of the antimicrobial activities of four commercial mouthwashes. J. Clin. Dent., V:103-105, 1995.

Settembrini L., Gultz J., Boylan R., Scherer W. Antimicrobial activity produced by six dentifrices. Gen. Dent.,
46:286-8, 1998.

Gultz J., Do L., Boylan R., Kaim J., Scherer W. Antimicrobial activity of cavity disinfectants. Gen. Dent., 47:187-90, 1999.

Adamo, H.L., Buruiana, R., Schertzer, L., Boylan, R.J. A comparison of MTA, Super-EBA, composite and amalgam as root-end filling materials using a bacterial microleakage model. Int. Endo. J.,32:197-203, 1999.

Russell, S.L., Boylan, R.J., Kaslick, R.S., Scannapieco, Katz, R.V. Respiratory pathogen colonization of the dental plaque of institutionalized elders. Spec. Care Dent., 19:128-134, 1999.


Periodontal Wound Healing


Ronald G. Craig
Associate Professor of Basic Sciences and of Periodontics
Graduate Co-Coordinator
__________________________________________________________________________________________

1974 B.S.            University of Connecticut (Storrs)
1978 D.M.D.       University of Pennsylvania
1987 Ph.D.          University of Connecticut (Farmington)
1978-80 G.P.R.   University of Connecticut Health Center, (Farmington)
1980-87               Department of Periodont., U. Connecticut, School of Dental Medicine
1987-1989           Dept. of Biochemistry, U. Pennsylvania, School of Dental Medicine
1989-                   NYU College of  Dentistry, Dept. of  Basic Science and Craniofacial Biology, and Dept. of Periodontology
 ____________________________________________________________
Our laboratory studies cell and molecular biology of wound healing in the periodontal environment. The techniques used include tissue culture, protein purification, antibody developing, and cloning.
 

Relevant Publications:

Craig, R.G., Rowe, D.W., Peterson, D.N., Kream, B.E. Insulin increases the steady state levels of (I) procollagen mRNA in the osteoblast-rich segment of fetal rat calvaria. Endocrinol., 125:1430-1437, 1989.

Rabinowitz, J.L., Craig, R.G. Changes in whole body lipid composition in a murine model of insulin-dependent diabetes mellitus. Metabolism, 38:777-780, 1989.

Rabinowitz J.L., Sheridan, O., Craig, R.G., Feldman, R., Grossman, E.R., Harvey, C.E., Haskins, M.E. Lipid composition and biosynthesis in the gingiva of the domestic cat. J. Periodontol., 62:496-498, 1991.

LeGeros, R.E., Craig, R.G. Strategies to affect bone remodeling osseointegration, "Proceedings of an NIH Sponsored Workshop on Osteoporosis and Oral Bone Loss. J. Bone Min. Res., 8:583-598, 1992.

Craig, R.G., Zuroff, M., Rosenberg, P.A. The effect of endodontic materials on periodontal ligament cell proliferation, alkaline phosphatase activity and extracellular matrix proteins synthesis in vitro. J. Endodont., 23:494-498,1997.

Craig RG. Yu Z. Xu L. Barr R. Ramamurthy N. Boland J. Schneir M. Golub LM. A chemically modified tetracycline
inhibits streptozotocin-induced diabetic depression of skin collagen synthesis and steady-state type I procollagen mRNA.
Biochim. Biophys. Acta. 1402:250-60, 1998.

Craig RG. LeGeros RZ. Early events associated with periodontal connective tissue attachment formation on titanium and
hydroxyapatite surfaces. J. Biomed. Mat. Res.47:585-94, 1999.

Craig RG. Advances in biomaterials from 1957 to 1997. J Oral Rehabil. 26:841-6, 1999.

Mohsen NM, Craig RG, Filisko FE. The effects of different additives on the dielectric relaxation and the dynamic mechanical properties of urethane dimethacrylate. J Oral Rehabil. 27:250-68, 2000.

Mohsen NM, Craig RG, Filisko FE. The effects of moisture on the dielectric relaxation of urethane dimethacrylate polymer and composites. J Oral Rehabil. 28:376-92, 2001.

Craig RG, Boylan R, Yip J, Bamgboye P, Koutsoukos J, Mijares D, Ferrer J, Imam M, Socransky SS, Haffajee AD. Prevalence and risk indicators for destructive periodontal diseases in 3 urban American minority  populations.  J Clin Periodontol. 28:524-35, 2001.
 



 

Ion Channel Properties of Mineralogenic Cells

Robert M. Davidson
Associate Professor and Chair, Department of Periodontology
________________________________________________________________________________

1965 B.A.          Drew University
1971 D.D.S.       Fairleigh Dickinson University
1987 Ph.D.         State University NY at Buffalo (Neurobiology)
1988 Postdoc     State University NY at Buffalo (Biophysics)
1988-1996         University of Connecticut School of Dental Medicine
1996-                 New York University College of Dentistry, Dept. of Basic Science and Craniofacial Biology, and Dept. of Periodontology
 ____________________________________________________________

 One area of interest in our laboratory focuses on the ionic mechanisms that regulate activity of mineralogenic cells in bones and teeth. Specifically, we are interested in the physiological and kinetic properties of cation channels in osteoclast and osteoblast cells found in bone, as well as odontoblast cells from dental pulp. A second area of interest focuses on the immunohistochemical and physiological properties of dental pulp cells and their relation to sensory transduction in teeth. In particular, we are interested in the voltage-gated sodium channel found in the non-odontoblast dental pulp cell. We use a combination of patch-clamp recording techniques, fluorometric imaging, and immunohistochemistry.
 

Relevant Publications:

Davidson, R.M. Membrane stretch activates a Ca2+-dependent high-conductance K+ channel in osteoblast-like cells. J. Memb. Biol., 131:81-92, 1993.

Davidson, R.M. Potassium currents in cells derived from human dental pulp. Arch. Oral Biol., 38:803-811, 1993.

Davidson, R.M. Neural form of voltage-dependent sodium current in human cultured dental pulp cells. Arch. Oral Biol.,39:613-620, 1994.

Zhang, J., Loew, L.M. Davidson R.M. Sodium channels show faster activation in growth cone than in soma of a mammalian neuroblastoma cell. Biophys. J., 71:2501-2508, 1996.

Davidson, R.M, Lingenbrink, P.A., Norton, L.A. Continuous mechanical loading alters properties of mechanosensitive channels in G292 osteoblastic cells. Calicif. Tissue Inter., 59:500-504, 1996.

Gofa, A., Davidson, R.M. NaF stimulates proliferation and potentiates a K+-selective ion channel in G292 osteoblastic cells. J. Memb. Biol., 149:211-219, 1996.

Zhang, J., Davidson, R.M., Wei, M., Loew, L.M. Membrane electric properties by combined patch clamp and fluorescence ratio imaging in single neurons. Biophys. J., 74:48-53, 1998.

Guo, L., Davidson, R.M. Potassium and chloride channels in freshly isolated rat odontoblasts. J. Dent. Res., 77:341-350, 1998.

Guo L. Davidson RM. Extracellular Ca2+ increases cytosolic free Ca2+ in freshly isolated rat odontoblasts. J. Bone Mineral  Res.14:1357-66, 1999.

Guo L. Berry JE. Somerman MJ. Davidson RM. A novel method to isolate odontoblasts from rat incisor. Calc.
Tiss.Int.66:212-6, 2000.

Davidson RM, Guo L. Calcium channel current in rat dental pulp cells. J Membr Biol. 178:21-30, 2001.


Biomineralization and Material Science

John Spencer Evans
Associate Professor of Basic Sciences (Biochemistry) and of Chemistry (Graduate School of Arts and Science)
____________________________________________________________

1978 B.S.         Northwestern University
1982 D.D.S.     University of Illinois
1993 Ph.D.       California Institute of Technology
1994 Postdoc,  California Institute of Technology
1995-               New York University College of Dentistry, Dept. of Basic Science and Craniofacial Biology, and Graduate School of Arts and Science, Dept. of Chemistry
________________________________________________________________

Our research approach to biomineralization involves biopolymer-directed material synthesis; extracellular matrix protein structure and function; NMR spectroscopy, bio-organic chemistry, and molecular and ab-initio modeling.
 

Relevant Publications:

Rich, M., Evans, J.S. Molecular dynamics simulations of adipocyte lipid binding protein (ALBP): Fatty acid-protein sidechain interaction and acyl chain unsatturation stabilize protein-lipid interactions. Biochemistry, 35:1506-1515, 1996.

Xu, G., Evans, J.S. The application of "excitation sculpting" in the construction of selective one-dimensional homonuclear coherence transfer experiments. J. Mag. Res. Series B, 111:183-185, 1996.

Reeves, N.J. Evans, J.S. CHASM (Chain Alignment on the Surface of Materials: An algorythm for predicting polymer and polypeptide conformations at interfaces. J. Phys.Chem., 100:17297-17304, 1996.

Reeves, N.J. Evans, J.S. Polypeptide interactions at ice and biomineral interfaces are defined by secondary-structure-dependent chain orientations. J. Phys. Chem. B, 101: 6665-6669,1997.

Evans, D.A., Evans, J.S.  Host-Guest Interactions Influence Stability of the Rebek"Tennis Ball" Dimer Complex.  J. Org. Chem., 63: 8027-8030, 1998.

Xu, G., Evans, J.S.  Model Peptide Studies of Sequence Repeats Derived from the Intracrystalline Biomineralization Protein, SM50.  I. GVGGR and GMGGQ Repeats.  Biopolymers, 49:303-312, 1999

Xu, G., Evans, J.S. PFG-omega1-Filtered TOCSY Experiments for the Determination of Long-Range Heteronuclear and Coupling Constants, and, Estimation of J-Coupling "Crosstalk" Artifacts in 2-D 1-Filtered "E. COSY-Style" Spectra.  J. Mag. Res., 138:127-134,1999.

Zhang B. Xu G. Evans JS. A kinetic molecular model of the reversible unfolding and refolding of titin under force
extension. Biophys. J. 77:1306-15, 1999.

Xu G. Zhang B. Evans JS. PFG-omega1-filtered TOCSY experiments for the determination of long-range heteronuclear and homonuclear coupling constants and estimation of J-coupling "crosstalk" artifacts in 2-D omega1-filtered "E. COSY-style" spectra. J. Magnet. Reson.138:127-34, 1999.

Zhang B, Xu G, Evans JS. Model peptide studies of sequence repeats derived from the intracrystalline biomineralization protein, SM50. II. Pro,Asn-rich tandem repeats. Biopolymers.54:464-75, 2000.

Zhang B, Evans JS. Modeling AFM-induced PEVK extension and the reversible unfolding of Ig/FNIII domains in single and multiple titin molecules. Biophys J. 80:597-605, 2001.


Chemical Carcinogenesis and Mutagenesis


Joseph B. Guttenplan
Professor of Basic Sciences (Biochemistry)
____________________________________________________________

1965 B.S.            Brooklyn College
1970 M.S.           Brandeis University
1970 Ph.D.          Brandeis University
1969-71 Postdoc Max Planck Institute for Biophysical Chemistry (Gottingen)
1971-73 Postdoc University of California (Berkeley)
1974-                   New York University College of  Dentistry, Dept. of  Basic Science and Craniofacial Biology
_________________________________________________________________

Research in my laboratory focuses on measuring mutations in tissues of lacZ transgenic mice, chemoprevention of mutagenesis, development of high sensitivity fluorescence assays for detection of modified nucleotides from DNA, the metabolism of carcinogens, interactions of carcinogens with DNA, detection of carcinogen-DNA adducts, and determination of mutational spectra of carcinogens. Laboratory methodologies include high performance liquid chromatography, mutagenesis, colony hybridization probing, enzyme assays, DNA sequencing, and 32P-post-labelling.
 

Relevant Publications:

Chung, F.L., Chen, H. J.C., Guttenplan, J.B., Nishikawa. 2, 3-epoxy-4-hydroxynonanal as a potential initiating agent of lipid peroxidation. Carcinogenesis, 14:2073-2077, 1993.

Jiao, J., Guttenplan, J.B., Glickman, B.W., Anderson, M.W., Xin, L-Y, Zielenska, M. Mutational specificities of environmental carcinogens in the lacI gene of E. coli VII: The host-mediated assay and its comparison with in vitro mutagenesis induced by 4- (methylnitrosamino) -1- (3-pyridyl)-1-butanone. Mol. Carcinogenesis, 8:127-131, 1993.

Tinwell, H., Paton, D., Guttenplan, J.B., Ashby, J. The unexpected genetic toxicity to rodents of the N’, N’- dimethyl analogues of MU and ENU. Environ. Mol. Mutagen., 27:202-211, 1996.

Nath, R., Ocando, JE, Guttenplan, J.B. Chung, F-L., 1,N2-Propanodeoxyguanosine adducts: Potential new biomarkers of smoking induced DNA damage in human oral tissue, Cancer Res., 58:581-584, 1998.

Bhaumik, M., Harris, T., Johnson, L. Guttenplan, J.B., Rogler C., Stanley, P. Progression of chemically induced hepatoma is severely retarded in mice lacking GlcNAc on N-glycans. Cancer Res., 58:2881-2887, 1998.

Kosinska, W., von Pressentin, M.d.M., Guttenplan, J.B. Comparative mutagenicity of benzo(a)pyrene in breast and oral tissues of lacZ mice. Canrcinogenesis, 20:1103-1106, 1999.

von Pressentin MM. Kosinska W. Guttenplan JB. Mutagenesis induced by oral carcinogens in lacZ mouse
(MutaMouse) tongue and other oral tissues. Carcinogenesis. 20:2167-70, 1999.

von Pressentin, M.M., El-Bayoumy, K., Guttenplan JB. Mutagenic activity of 4-nitroquinoline-N-oxide in upper
aerodigestive tissue in lacZ mice (MutaMouse) and the effects of 1, 4-phenylenebis(methylene)selenocyanate. Mut. Res. 466:71-80, 2000.

Guttenplan JB, Chen M, Kosinska W, Thompson S, Zhao Z, Cohen LA. Effects of a lycopene-rich diet on spontaneous and benzo[a]pyrene-induced mutagenesis in prostate, colon and lungs of the lacZ mouse. Cancer Lett. 164:1-6, 2001.

von Pressentin MM, Chen M, Guttenplan JB.  Mutagenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-nitrosonornicotine in lacZ upper aerodigestive tissue and liver and inhibition by green tea. Carcinogenesis 22:203-6, 2001.



The Role of Mitochondrial Channels in Programmed Cell Death;
Molecular Studies of Two Mitochondrial Ion Channels Involved in Protein Import

Kathleen Walsh Kinnally
Professor of  Basic Sciences (Biophysics)
_____________________________________________________________________________
1974      B.S.    University at Albany   (Biology)
1977      Ph.D.  University at Albany    (Biology)
1977-80           Amer. Cancer Soc. Postdoctoral Fellow,   Rensselaer Polytechnic Institute (Chemistry)
1980-87           Research Scientists - Univ. at Albany, Albany, NY
1987-2000       Assistant/Associate Professor Univ. at Albany, Albany, NY, (Biology/Biomedical Sciences)
1993-2000       Research Scientist Wadsworth Center, NY State Dept. Health
2000-               New York University College of Dentistry, Dept. of Basic Science and Craniofacial Biology
___________________________________________________________________________

This laboratory is examining the translocation of proteins across membranes.  One project focuses on the fundamental mechanisms of protein import into mitochondria using electrophysiological techniques.  The role of mitochondrial channels in programmed cell death is examined with a variety of additional techniques including microinjection and microsurgery of single cells, time-lapse video microscopy (fluorescence and phase), and flow cytometry. Understanding the cell death process will facilitate development of therapies that enable activation of this cascade to control the growth of malignancies and blockade of the pathway to reduce the volume of cell death after ischemic injury, e.g., stroke or heart attack.

Selected Publications
Lohret, T.A. and Kinnally, K.W. Targeting peptides transiently block a mitochondrial channel. J. Biol. Chem. 270:15950-15953, 1995.

Shao, L., Kinnally, K.W., Mannella, C.A. Circular dichroism studies of open and closed states of the mitochondrial channel, VDAC. Biophys. J. 71:778-786, 1996.

Lohret, T.A., Murphy, R.C., Drgoñ, T., Kinnally, K.W. Evidence that the mitochondrial multiple conductance channel, MCC, is not related to the adenine nucleotide translocator. J. Biol. Chem., 271:4846-4849, 1996.

Lohret T.A., Jensen R.E., Kinnally K.W. Tim23, a protein import component of the mitochondrial inner membrane, is
required for normal activity of the multiple conductance channel, MCC. J. Cell Biol. 137:377-86, 1997.

Jensen R.E., Kinnally K.W. The mitochondrial protein import pathway: are precursors imported through membrane
channels?. J. Bioenergetics Biomembr.29:3-10, 1997.

Campo M.L., Tedeschi H., Muro C., Kinnally K.W. Effects of carbonyl cyanide phenylhydrazones on two mitochondrial
ion channel activities. J. Bioenergetics Biomembr.29:223-31, 1997.

Koppel D.A., Kinnally K.W., Masters P., Forte M., Blachly-Dyson, E., Mannella C.A. Bacterial expression and
characterization of the mitochondrial outer membrane channel. Effects of n-terminal modifications. J. Biol.
Chem. 273:13794-800, 1998.

Murphy R.C., Diwan J.J., King M., Kinnally K.W. Two high conductance channels of the mitochondrial inner membrane
are independent of the human mitochondrial genome. FEBS Lett. 425:259-62, 1998.

Kushnareva Y.E., Campo M.L., Kinnally K.W. Sokolove PM. Signal presequences increase mitochondrial permeability
and open the multiple conductance channel. Arch. Biochem Biophys. 366:107-15, 1999.

Kinnally, K.W. The protein translocation channels of mitochondria; the Tim and Tom channels. In Polymer Structure and Transport in Confined Spaces, Edited by Kasianowicz, J.J., Kluwer Press, 2000.

Kinnally K.W., Muro C., Campo, M.L.  MCC and PSC, the putative protein import channels of mitochondria. J. Bioenerg. Biomemb., 32:47-54, 2000.


 Formation and Stability of Biological and Synthetic Calcium Phosphates - Effect of Fluoride, Magnesium, Carbonate, Strontium and Other Trace Elements

Racquel Z. LeGeros
Linkow Professor of Implant Dentistry and of Restorative and Prosthodontic Sciences (Biomaterials) and Acting Chair of Dept. of Biomaterials and Biomimetics.
_______________________________________________________________________

1954 B.S.       Adamson University (Manila)
1957 M.S.      New York University
1959               Brooklyn Polytechnic Institute
1967 Ph.D.     New York University
1968               New York University College of Dentistry, Dept. of Biomaterials and Biomimetics
 _______________________________________________________________________

Our research program is oriented toward the elucidation of the effect of carbonate, magnesium, fluoride, strontium, zinc, and other trace elements on the formation and stability of calcium phosphates (substituted and unsubstituted apatite, amorphous calcium phosphates (ACP), dicalcium phosphate dihydrate (DCPD), octacalcium phosphate (OCP), tricalcium phosphate (TCP) relevant to dental caries, dental calculus and pathological calcifications; characterization of mineral phases of calcified tissues (normal and pathological); and preparation/characterization of calcium phosphate materials (including coatings on implants) used for bone repair, augmentation and substitution.

Our methodology includes X-ray diffraction, infrared spectroscopy, thermogravimetry, atomic absorption, scanning electron microscopy, chemical analyses, studies using pHstat and ion selective electrodes, and syntheses.
 

Relevant Publications:

LeGeros, R.Z. Calcium phosphates in oral biology and medicine, Vol. 15, Monographs in Oral Sciences, Karger, Basel, 1991.

LeGeros, R.Z., Kijkowska, R., Bautista, C., LeGeros, J.P. Synergistic effects of magnesium and carbonate on properties of biological and synthetic apatites. Conn. Tiss. Res., 33:203-209, 1995.

LeGeros, R.Z., LeGeros, J.P., Kim, Y., Kijkowska, R., Zheng, R., Bautista, C., Wong, J.L. Calcium phosphates in plasma-sprayed HA coatings. Cer. Trans., 48:173-189, 1995.

Okazaki, M., LeGeros, R.Z. Properties of heterogenous apatites containing magnesium, fluoride and carbonate. Adv. Den. Res., 10:252-259, 1996.

LeGeros R.Z., Sakae, T., Bautista, C., Retino, M., LeGeros, J.P. Magnesium and carbonate in enamel and synthetic apatites. Adv. Dent. Res., 10:225-231, 1996.

Daculsi, G., Bouler, J.M., LeGeros, R.Z. Adaptive crystal formation in normal and pathological calcifications in synthetic calcium phosphate and related biomaterials. Int. Rev. Cytol.,172:129-191, 1997.

Wu, L.N., Genge, B.R., Dunkelberger, D.G., LeGeros, R.Z., Concannon, B., Wuthier, R.E. Physicochemical characterization of the nucleational core of matrix vesicles. J. Biol. Chem., 272:4404-4411, 1997.

LeGeros, R.Z., LeGeros, J.P. (Eds.) Bioceramics 11, World Scientific Publishing Co., Singapore, 1998.

Takagi, T., Ogasawara, T., Tagami, J., Akao, M., Kuboki, Y., Nagai, N., LeGeros, R.Z. pH and carbonate levels in developing enamel. Conn. Tiss. Res., 38:181-187, 1998.

LeGeros, R.Z., Bleiwas, C.B., retino, M., Rohanizadeh, R., LeGeros, J.P. Zinc effect on the in vitro formation of calcium phosphates: relevance to clinical inhibition of calculus formation. Am. J. Dent., 12:65-70, 1999.

Rohanizadeh R. LeGeros RZ. Fan D. Jean A. Daculsi G. Ultrastructural properties of laser-irradiated and heat-treated
dentin. J. Dent. Res. 78:1829-35, 1999.

Ryan LM. Cheung HS. LeGeros RZ. Kurup IV. Toth J. Westfall PR. McCarthy GM. Cellular responses to whitlockite.
Calc.Tiss.Int.65:374-7, 1999.

Craig RG., LeGeros RZ. Early events associated with periodontal connective tissue attachment formation on titanium
and hydroxyapatite surfaces. J. Biomed. Mat. Res. 47:585-94, 1999.

Rohanizadeh, R., LeGeros, R.Z., Bohic, S., Pilet, P., Barbier, A., Daculsi, G. Ultrastructural properties of bone mineral of
control and tiludronate-treated osteoporotic rat. Calcified Tissue International. 67:330-6, 2000.

Bouler, J.M., LeGeros, R.Z., Daculsi, G. Biphasic calcium phosphates: influence of three synthesis parameters on the
HA/beta-TCP ratio. J. Biomed. Mat. Res. 51:680-4, 2000.



 

The Molecular Biology of the Major Histocompatibility Complex Class I Antigens

Jane McCutcheon
Associate Professor of Basic Sciences (Immunology), Graduate Co-Coordinator.
_____________________________________________________________________

1980 B.G.S.                   University of Iowa
1984 D.D.S.                  University of Iowa
1991 Ph.D.                    University of Iowa
1991-94 Postdoc          Cancer Research Institute Fellow, Stanford University
1994-                            New York University College of Dentistry, Dept of Basic Science and Craniofacial Biology
1999 Affiliate Member,  Department of Biology, College of Arts and Sciences, New York University
_____________________________________________________________________

I am interested in the regulation and biological relevance of human major histocompatibility complex (MHC) class I antigens. Class I proteins are found on the surface of most nucleated cells and function to present small endogenously processed peptides to roving cytotoxic T lymphocytes. Human MHC class I contains three loci; the protein products are co-dominantly expressed on cell surfaces. While protein products from two of the loci, HLA-A and B, are well characterized, HLA-C proteins have not been well defined by structural or functional studies. As recent studies have shown that HLA-C proteins are regulated by short mRNA half-lives and natural killer cells recognize specific HLA-C proteins, these data suggest that HLA-C proteins play an important role in immune responses.
 
 

Relevant Publications:

McCutcheon, J.A., Parham, P. An assessment of the functional significance of mutations in the pockets of the peptide binding groove of HLA-A*0201. J. Cell. Biochem., suppl 16D, 1992.

McCutcheon, J.A., Lutz, C.T. Mutagenesis around residue 176 on HLA-B*0702 characterizes multiple distinct epitopes for anti-HLA antibodies. Human Immunol., 35:125-131, 1992.

McCutcheon, J.A., Smith, K.D., Valenzuela, A., Aalbers, K., Lutz, C.T. HLA-B*0702 antibody epitopes are affected indirectly by distant antigen residues. Human Immunol., 36:69-75, 1993.

Lutz, C.T., Smith, K.D., Greazel, N.S., Mace, B.E., Jensen, D.A., McCutcheon, J.A., Tahara, T., Hammerling, U., Nancy E. Goeken. Bw4-reactive and Bw6-reactive antibodies recognize a number of distinct HLA structures that partially overlap in the a-1 helix. J. Immunol., 153:4099-4110, 1994.

McCutcheon, J.A., Gumperz, J., Smith, K.D., Lutz, C.T. Parham, P. Low HLA-C expression at cell surfaces correlates with increased turnover of heavy chain mRNA. J. Exp. Med., 181:2085-2095, 1995.

Smith, K.D., Mace, B.E., Valenzuela, A, Figna, J.L., McCutcheon, J.A., Barbosa, J.A., Huczko, V.H., Engelhard, V.H., Lutz, C.T. Probing HLA-B7 conformational shifts induced by peptide-binding groove mutations and bound peptide with anti-HLA monoclonal antibodies. J. Immunol., 157:2470-2479, 1996.
 



 

Experimental Hematology/Endocrine Physiology


Martin Roy
Professor of Basic Sciences (Histology and Cell Biology)
_______________________________________________________________________

1968 B.S.   Brooklyn College
1973 M.S.  Brooklyn College
1979 Ph.D. New York University
1978 -        New York University College of Dentistry, Dept. of Basic Science and Craniofacial Biology
__________________________________________________________________

Our laboratory is involved in research concerning selenium as a biological response modifier of immune cell function in tumor cytodestruction. Among the techniques utilized in the laboratory are: interleukin 2 receptor assays; assays for the activity of cytotoxic lymphocytes, LAK cells, NK cells, and cytotoxic macrophages; assays for TNF, interferons, IL1 and IL2; maintenance of tumor cell lines; radioactive isotope technology; and histopathology. A second area of interest relates to developing methodologies for testing the biocompatibility of dental materials. Current testing is by the Hamster Cheek Pouch Irritability test, which was developed in our laboratory.
 

Relevant Publications:

Roy, M., Kiremidjian-Schumacher, L., Wishe, H.I., Cohen, M.W., Stoztky, G. Selenium supplementation enhances the expression of interleukin 2 receptor subunits and internalization of interleukin 2. Proc. Soc. Exp. Biol. Med., 202:295-301, 1993.

Roy, M., Kiremidjian-Schumacher, L., Wishe, H.I., Cohen, M.W., Stotzky, G. Supplementation with selenium and human immune cell functions. I. Effect on lymphocyte proliferation and interleukin 2 recepter expression. Biol. Trace Elem. Res., 41:103-114, 1994.

Roy, M., Kiremidjian-Schumacher, L., Wishe, H.I., Cohen, M.W., Stotzky, G. Supplementation with selenium restores age-related decline in immune cell function. Proc. Soc. Exp. Biol. Med., 209:369-375, 1995.

Kiremidjian-Schumacher, L., Roy, M., Wishe, H.I., Cohen, M.W., Stotzky, G. Supplementation with selenium augments the function of natural killer and lymphokine activated killer cells. Biol. Trace Elem. Res., 52:227-239, 1996.

Kiremidjian-Schumacher, L., Roy, M. Selenium and immune function. In: Barth, C.A., Frontiers in Nutrition Research. Zeitschrift fur Ernahrungswissenschaft 37 (Suppl. 1):50-56, 1998.

Sumareva, R., Ukrainsky, G., Kiremidjian-Schumacher, L., Roy, M., Wishe, H., Steinfeld, A.D., Cooper, J.S. Effect of combined adoptive immunotherapy and radiotherapy on tumor growth. Radiat. Oncol. Investig., 7:22-29, 1999.

Landesberg R., Roy M., Glickman RS. Quantification of growth factor levels using a simplified method of platelet-rich
plasma gel preparation. J. Oral Maxillofac. Surg. 58:297-300, 2000.



Multistage Carcinogenesis,
Premalignancy and Oral Cancer

Peter G. Sacks, Associate Professor of Basic Sciences
____________________________________________________________________
1968            B.A. Queens College
1968-69 & 1973-78      Ph.D. Syracuse University
1978-81      Post-doc. University of Rochester School of Medicine and Dentistry
1981-84      Research Associate IV- Wadsworth Laboratories, NY State Dept. of Health
1984-91      Assistant Professor, University of Texas M. D. Anderson Cancer Center
1991-99      Associate Laboratory Member, Memorial Sloan-Kettering Cancer Center
1999-          New York University College of Dentistry, Dept. of Basic Science and Craniofacial Biology
____________________________________________________________________
 

My laboratory is interested in the biology of oral cancer.  Recent studies have focused on chemoprevention, a therapeutic modality that has shown clinical efficacy with precancereous oral tissues.  We have established an in vitro human multistage carcinogenesis model for oral cancer, consisting of primary cultures of normal oral epithelial cells, cell lines developed from dysplastic leukoplakia (considered premalignant) and oral squamous carcinoma cell lines.   We are using this model to examine specific preventive agents with respect to efficacy and mechanisms of action.  Additionally, the biological basis of precancer is ill understood and our “premalignant” oral cell systems, the first such in the U.S., provide a relevant tool for beginning to understand the biology of the premalignant state.

Relevant Publications

Sacks, P.G., Parnes, S.M., Price, J.C., Risemberg, H., Goldstein, J.C., Parsons, D.F. In vitro control of differentiation by calcium in explants of human and murine epithelial tissues.  In Vitro 21:99-107, 1985.

Sacks, P.G., Parnes, S.M., Gallick, G.E., Mansouri, .Z, Lichtne,r R., Satya-Prakash, K.L., Pathak, S., Parsons, D.F.  Establishment and characterization of two new squamous cell carcinoma cell lines derived from tumors of the head and neck.  Cancer Res., 48:2858-2866, 1988.

Sacks, P.G., Harris, D., Chou, T-C. Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: a  rationale for combination therapy with chemotherapeutic agents. Int. J. Cancer, 61:409-415, 1995.

Sacks, P.G. Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck.  Cancer and Metastasis Reviews 15:27-51, 1996.

Sacks, P.G., Savage, H.E., Levine, J., Kolli, V.R., Alfano, R.R., Schantz, S.P. Native cellular fluorescence identifies terminal squamous differentiation of normal oral epithelial cells in culture: a potential chemopreventive biomarker. Cancer Letters 104:171-181, 1996.

Xu, L., Schantz, S.P., Edelstein, D., Sacks, P.G.  A simplified method fot the routine culture of normal oral epithelial (NOE) cells from upper aerodigestive mucosa.  Methods in Cell  Science 189:1-9, 1996.

Spingarn, A., Sacks, P.G., Kelley, D., Dannenberg, A.J., Schantz, S.P. Synergistic effects of 13-cis retinoic acid and arachidonic acid cascade inhibitors on growth of head and neck squamous cell carcinoma in vitro. Otolaryngol-Head Neck Surg. 118:159-164, 1998.

Khafif, A., Schantz, S.P, Chou, T-C., Edelstein, D., Sacks, P.G. Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells. Carcinogenesis, 19:419-424, 1998.

Khafif, A., Schantz, S.P., Al-Rawi, M. Edelstein, D., Sacks, P.G. Green tea regulates cell cycle progression in oral leukoplakia. Head & Neck 20:528-534, 1998.

Ganesan S. Sacks PG. Yang Y. Katz A. Al-Rawi M. Savage HE. Schantz SP. Alfano RR. Native fluorescence spectroscopy of normal and malignant epithelial cells. Cancer Biochem. Biophys.16:365-73, 1998.

Carew JF. Federoff H. Halterman M. Kraus DH. Savage H. Sacks PG. Schantz SP. Shah JP. Fong Y. Efficient gene transfer to human squamous cell carcinomas by the herpes simplex virus type 1 amplicon vector. Am. J. Surg. 176:404-8, 1998.

Gillenwater A. Xu XC. Estrov Y. Sacks PG. Lotan D. Lotan R. Modulation of galectin-1 content in human head and neck squamous carcinoma cells by sodium butyrate. Int. J. Cancer. 75:217-24, 1998.

Chan G. Boyle JO. Yang EK. Zhang F. Sacks PG. Shah JP. Edelstein D. Soslow RA. Koki AT. Woerner BM. Masferrer JL. Dannenberg AJ. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res. 59:991-4, 1999.

Mestre JR. Chan G. Zhang F. Yang EK. Sacks PG. Boyle JO. Shah JP. Edelstein D. Subbaramaiah K. Dannenberg AJ. Inhibition of cyclooxygenase-2 expression. An approach to preventing head and neck cancer. Ann New York Acad. Sci. 889:62-71, 1999.

Michaluart P. Masferrer JL. Carothers AM. Subbaramaiah K. Zweifel BS. Koboldt C. Mestre JR. Grunberger D. Sacks PG. Tanabe T. Dannenberg AJ. Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Res. 59:2347-52, 1999.



The influence of aging, systemic diseases, and medications on oral health and function

Jonathan A. Ship
Professor of Oral Medicine, Director of the Blustone Center for Clinical Research
_________________________________________________________________________________________

1976-80         B.A. Anthropology (Cum Laude) Univ. Pennsylvania,
1980-84         D.M.D.Univ. Pennsylvania
1984-85         GPR Montefiore Medical Center, Bronx
1987-89         Fellowship in Oral Medicine & Clin. Dent. Res., NIH/NIDCR
_________________________________________________________________________________________

The focus of my research has been to try and gain a better understanding of the influence of aging, systemic diseases, and medications on oral health and function. My research investigations began with a systematic approach to assessing oral conditions in healthy populations of different-aged adults.  Research findings demonstrated that specific systemic conditions, medications, radiotherapy, and chemotherapy had greater adverse affects on the health and function of the oral cavity than the simple chronological passing of time in healthy adults. Since saliva plays a central role in the protection and preservation of oral and pharyngeal health, particularly in the aging adult, my laboratory has examined multiple sociodemographic and biological factors: menopause, dehydration, diabetes, hypothyroidism, Sjögren's syndrome, menopause, periodontal diseases, medications, and head and neck radiotherapy.
Current research projects involve the interaction of diabetes and oral health, new therapies for oral mucosal lesions, salivary function in aging adults, and head and neck radiotherapy techniques to preserve saliva in cancer patients.
 

Relevant Publications:

Ship JA.  The Influence of Aging on Oral Health and Consequences for Taste and Smell.  Phys Behav 1999;66(2):209-215.

Henson BS, Eisbruch A, D’Hondt E, Ship JA.  Two Year Longitudinal Study of Parotid Salivary Flow Rates in Head and Neck Cancer Patients Receiving Unilateral Neck Parotid-Sparing Radiotherapy Treatment.  Oral Oncology 1999;35:234-241.

Ship JA, Chavez EM, Gould KL, Henson BS, Sarmadi M.  Evaluation and Management of Oral Cancer.  Home Healthcare Consultant 1999;6(4):2-12.

Ship JA, Fischer D.  Metabolic Indicators of Hydration Status in the Prediction of Parotid Salivary Gland Function. Arch Oral Biol 1999;44:343-350

Ship JA, Fox PC, Michalek JE, Cummins MJ, Richards AB, and the IFNá protocol study group.  Treatment of Primary Sjögren’s Syndrome with Low-Dose Natural Human Interferon Alpha (IFNá) Administered by the Oral Mucosal Route - Results of a Phase 2 Clinical Trial.  J Inter Cytokine Res 1999;19:943-951.

Eisbruch A, Ten Haken R, Kim HM, Marsh, Ship JA. Dose, Volume, and Function Relationships in Parotid Salivary Glands Following Conformal and Intensity Modulated Irradiation of Head and Neck Cancer. Int J Radiation Oncology Biol Phys 1999;45:577-587.

Ship JA, Chavez EM, Doerr PA, Henson BS, Sarmadi M.  Recurrent Aphthous Stomatitis.  Quintessence Int 2000;35:95-112

Ghezzi EM, Wagner-Lange LA, Schork MA, Metter EJ, Baum BJ, Streckfus CF, Ship JA.  Longitudinal Influence of Menopause, Hormone Replacement Therapy, and Other Medications on Parotid Flow Rates in Healthy Women.  J Gerontol Med Sci 2000;55A:M34-42

Ghezzi EM, Ship JA.  Dementia and Oral Health.  Oral Surg Oral Med Oral Path Oral Radiol Endo 2000;89(1):2-5

Chavez EM, Taylor GT, Borrell LN, Ship JA.  Salivary Function and Glycemic Control in Older Diabetics.  Oral Surg Oral Med Oral Path Oral Radiol Endo 2000;89(3):305-311.

Ghezzi EM, Chavez EM, Ship JA.  General Anesthesia Protocol for the Dental Patient: Emphasis for Older Adults. Spec Care Dent 2000;20(3):81-108.

Ship JA, Chavez EM.  Management of Systemic Diseases and Chronic Impairments in Older Adults: Oral Health Considerations.  Gen Dent 2000;Sept-Oct:555-565.

Ghezzi EC, Lange LA, Ship JA.  Determination of Variation of Stimulated Salivary Flow Rates.  J Dent Res 2000;79(11):1874-8

Chavez EM, Ship JA.  Sensory and Motor Deficits in the Elderly: Impact on Oral Health.  J Pub Health Dent 2000;60(4):297-303.

Ghezzi EM, Ship JA.  Systemic Diseases and Their Treatments in the Elderly: Impact on Oral Health.  J Pub Health Dent 2000;60(4):289-296.

Pai SC, Ghezzi EM, Ship JA.  Development of a Visual Analogue Scale Questionnaire for Subjective Assessment of Salivary Dysfunction.  Oral Surg Oral Med Oral Pathol Oral Radiol Endo 2001;91:311-316.

Chavez EM, Borrell LN, Taylor GW, Ship JA.  A Longitudinal Analysis of Salivary Flow in Older Adults with Type 2 Diabetes. Oral Surg Oral Med Oral Pathol Oral Radiol Endo 2001;91:166-173.

Henson BS, Inglehart MR, Eisbruch A, Ship JA.  Preserved Salivary Output and Xerostomia-Related Quality of Life in Head and Neck Cancer Patients Receiving Parotid-Sparing Radiotherapy. Oral Oncol 2001;37:84-93.

Eisbruch A, Kim HM, Terrell JE, Marsh LH, Dawson LA, Ship JA.   Xerostomia and its Predictors Following Parotid-Sparing Irradiation of Head and Neck Cancer.  Int J Rad Oncol Biol Phys 2001;50(3):695-704.


Peripheral Mechanisms of Taste Perception;
Chemical Communications
 

Andrew I. Spielman
Professor and Chair, Dept. of Basic Science and Craniofacial Biology
Director, Graduate Studies in Oral Biology.
_______________________________________________________________________

1974         D.M.D., University of Medicine & Pharmacy, Tirgu Mures, Romania
1982         Cert. in Oral Surg., Technion Institute of Technology, Haifa, Israel
1985         M.S., University of Toronto, Toronto, Canada
1988         Ph.D., University of Toronto, Toronto, Canada
1988-89   Assist. Member, Monell Chemical Senses Center, Philadelphia
1989-92   Clinical Associate, University of Pennsylvania, School of Dental Medicine
1989-       New York University College of Dentistry, Dept. of Basic Science and Craniofacial Biology
1989-       Affiliate Member, Monell Chemical Senses Center, Philadelphia
_______________________________________________________________________

My laboratory is interested in the peripheral mechanisms of  taste transduction, primarily that of the bitter taste. We study taste signal transduction mechanisms using a Quench Flow Module, and by monitoring generation of second messengers such as cAMP, IP3 and cGMP that accumulate in taste cells within milliseconds after gustatory stimulation.

We are also interested in the role of odorant-binding proteins in saliva, serum, and sweat that carry volatile messengers, important in human chemical communication and possible pheromone signaling. We have purified and characterized several odorant-binding proteins (ASOB) from sweat, serum, and saliva. These proteins carry attached ligands which are small volatile compounds, e.g., 3-methyl-2-hexenoic acid, involved in sweat odor formation, and possibly, in the phenomenon of  "menstrual synchrony" observed among co-habiting females. Their role in serum and saliva remains to be elucidated.
 

Relevant Publications on Taste:

Spielman, A.I., Brand, J.G. (Editors). Experimental Cell Biology of Taste and Olfaction. CRC Press, Boca Raton, FL, pp. 437, 1995.

Spielman, A.I., Nagai, H., Sunavala, G., Dasso, M., Boekhoff, I., Breer, H., Huque, T., Whitney, G., Brand, J.G. Rapid kinetics of second messenger formation in bitter taste, Am. J. Physiology, (Cell Physiology), 270, C926-C931, 1996.

Spielman, A.I. Chemosensory function and dysfunction. Crit. Rev. Oral Biol. Med., 9:267-291, 1998.

Rosenzweig, S., Yan W., Dasso, M.,  Spielman, A.I. Possible novel mechanism for bitter taste mediated through cGMP. J. Neurophysiol.  81, 1661-1665, 1999.

Huang L., Shanker YG., Dubauskaite J., Zheng JZ., Yan W., Rosenzweig S., Spielman AI.,
Max M., Margolskee RF. Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nature (Neuroscience). 2:1055-62, 1999.

Yan, W., Sunavala, G., Rosenzweig, S., Dasso, M., Brand, J.G. and Spielman, A.I. Bitter taste transduced by PLCbeta2-dependent rise in IP3 and alpha-gustducin-dependent fall in cyclic nucleotides. Am. J. Physiol. – Cell Physiol., 2001, In press.
 

Relevant Publication on Chemical Communication and other collaborative work:

Zeng, C., Spielman, A.I., Vowels, B.R., Layden, J J., Beamann, K, Preti, G. A human axillary odorant is carried by Apolipoprotein D. Proc. Nat’l. Acad. Sci. USA, 93:6626-6630, 1996.

Preti, G., Spielman, A.I., Wysocki, C. The vomeronasal organ and human chemical communication. In: Encyclopedia of Human Biology, Vol. 8, (Editor, R. Dulbecco ), Second Edition, Academic Press Inc., San Diego, pp. 769-783, 1997.

Antipenko, A.Y., Spielman, A.I.,  Kirchberger, M.A.  Kinetic differences in the phospholamban-regulated  calcium pump when studied in crude and purified cardiac sarcoplasmic reticulum vesicles. J. Membr. Biol., 167: 257-265, 1999.

Antipenko, A.Y. , Spielman, A.I., Kirchberger, M.A. Actions of 6-Gingerol on the calcium pump in phosphorylated and unphosphorylated light canine cardiac sarcoplasmic reticulum vesicles. J. Pharm. Exp. Ther. 290:227-234, 1999.

Kobrinsky, E., Spielman, A.I., Rosenzweig, S., Marks, A. Ceramide triggers intracellular calcium release via the inositol-1,4,5-trisphosphate receptor in Xenopus laevis oocytes. Am. J. Physiol. 277(4 Pt 1): C655-72, 1999.


Cell-extracellular Matrix Interactions

Dr. Louis Terracio
Associate Dean for Research
Professor, Department of Basic Science and Craniofacial Biology
_______________________________________________________________________

1970         B.S. Geneva College
1975         Ph.D University of Minnesota
1978-80     Postdoc W. Alton Jones Cell Science Center & Tufts University
_______________________________________________________________________

My research interests center on Cell-Extracellular Matrix (ECM) interaction during development and in disease. In
particular I investigate the role of integrins in the formation of a normal myocardium. My lab uses recombinant adenovirus
to manipulate the integrins present on the cell surface of myocytes in culture and determine the role of specific integrins
on myofibrillogenesis and overall myocyte phenotype. The tissue culture findings are then tested in the intact heart using
whole embryo culture. I also study the role of mechanical stretch as a potential morphogenic signal using a tissue culture
model of aligned myocytes. We have demonstrated that thin aligned gels of collagen result in cultured myocytes taking
on an elongated rod shape similar to in vivo. This system allows us to investigate the effects of stretch on myocytes in
either the long axis of the cell or across the short axis, where the ECM-Integrin-Cytoskeletal complex is most abundant.
Data from this model coupled with data from a low shear culture environment has led us to attempt to tissue engineer
artificial myocardium. Finally my lab is also interested in the role of growth factors, specifically PDGF, in myocardial
development. Using genetically modified, knock out, animals and the culture models described above; we are
investigating the role of PDGF and integrins on myocardium formation.
Current Funding:  NIH: Regulation of Cardiac Myofibollogenesis; NIH: Interaction of PDGF and Integrins in the Heart
VCU PI D. Simpson DOD- Army: Tissue Engineering Artificial Skeletal Muscle Subcontract

Representative Publications:
Simpson D.G., M. Terracio, T.K. Borg and L. Terracio. Modulation of cardiac cell shape by composition and
orientation of the extracellular matrix in vitro. J. Cell Phy. 161:89-105, 1994.

Simpson, D.G., W.W. Sharp, T.K. Borg, R.L. Price, L. Terracio and A.M. Samarel. Mechanical Regulation of Cardiac Protein Degradation and Myofibrillar Structure. Am. J. of Physiology. 270:C1075-C1087, 1996.

Nakagawa, M., R.L. Price, C. Chintanawonges, D.G. Simpson, M.J. Horacek, T.K. Borg and L. Terracio. Analysis of
heart development in cultured rat embryos. J. Mol. Cell. Cardiol. 29:369-379, 1997.

Shiraishi, I., D.G. Simpson, W. Carver, T. Hirozane, L. Terracio and T.K. Borg. Inhibition of vinculin with antisense
oligodeoxynucleotides in fetal mouse cardiac myocytes. J. Mol. Cell. Cardio. 29:2041-2052, 1997.

Sharp, W.W., D.G. Simpson, T.K. Borg, A.M. Samarel and L. Terracio. Contractile activity and external mechanical
tension affect focal adhesion formation by cultured neonatal rat cardiac myocytes. Am. J. Physiol. 273(42): H546-556, 1997.

Borg, K.T., W. Burgess, L. Terracio and T.K. Borg. Expression of metalloproteases by cardiac myocytes and
fibroblasts in vitro. Cardiac Pathology. 6:261-269, 1997.

Price, R.L., W. Carver, D.G. Simpson, L. Fu, J. Zhao, T.K. Borg and L. Terracio. The Effects of Angiotensin II and
Specific Angiotensin Receptor Blockers on Embryonic Cardiac Development. Dev. Biology. 192:572-584, 1998.

Sussman, MA , S. Baque, C-S. Uhm, MP Daniels, R. Price, D. Simpson, L. Terracio, and L. Kedes Altered expression of tropomodulin in cardiomyocytes disrupts the sarcomereic structures of myofibrils. Circ. Res. 82:94-105,1998.

Simpson, D.G., T.A. Reaves, D-T Shih, W. Burgess, T.K. Borg and L. Terracio. Cardiac Integrins: The Ties That
Bind. Cardiovasc. Path. 3:135-143, 1998.

Kanekar, S., T. Hirozane, L. Terracio and T.K. Borg. Cardiac Fibroblasts: Form and Function. Cardiovasc. Path.
3:127-133, 1998.

Kanekar, S., J. Atance, T.K. Borg, W. Carver and L. Terracio.  Cardiac Cell-ECM interactions: A possible site for
mechanical signaling. In "Cardiac Hypertrophy". Fukei Press, Japan, 1999.

Price, R.L., J.D. Potts, T. E. Thielen, T. K. Borg and L. Terracio  Growth Factor Regulation of Embryonic, Fetal, and
Neonatal Cardiac Development. In: Cardiac Development R. Tomanek and R Runyan Ed s. JAI Press Stamford CT., 1999.

Simpson, DG, M Majeski, TK Borg and L Terracio. Regulation of Cardiac Myocyte Protein Turnover and
Myofibrillar Structure: In Vitro by Specific Directions of Stretch. Circulation Research 85(10):1-11, 1999.

Kanekar, S, TK Borg, L Terracio and W Carver. Modulation of Heart Fibroblast Migration and Collagen Gel
Contraction by IGF-1. Cell Adhesion and Communication 7:513-523, 2000.

Yost, MJ, D Simpson, K Wrona, S Ridley, HJ Ploehn, TK Borg and L Terracio. Design and Construction of a
Uniaxial Cell Stretcher. AJP - Heart. (accepted).
 



 

Molecular Biology and Defense Mechanisms of Human Saliva

Ching-Chung Tseng
Assistant Professor of Basic Sciences and Restorative and Prosthodontic Sciences.
_______________________________________________________________________

1982 D.D.S.         National Taiwan University, Taiwan.
1986 M.S.            State University of New York at Buffalo.
1992 PG Prostho. State University of New York at Buffalo.
1996 Ph.D.           State University of New York at Buffalo.
1996 Postdoc       State University of New York at Buffalo.
1996                     New York University College of Dentistry, Dept. of Basic Scienece and Craniofacial Biology
_______________________________________________________________________

Our research focuses on the molecular mechanisms of anti-HIV activity of human salivary secretory leukocyte protease inhibitor (SLPI); and genetic engineering and functional studies of salivary cystatins. We investigate the structure-function relationships of these defense molecules using biochemical methods, molecular biological techniques and recombinant DNA technology, protein engineering, circular dichroism spectroscopy, and computer molecular modeling. Our long-term goal is to develop saliva-derived therapeutic agents against infections, such as periodontal diseases and acquired immunodeficiency syndrome (AIDS).
 

Relevant Publications:

Loomis, R.E., Tseng, C.C., Bergey, E.J.,  Levine, M.J. N.m.r. Analyses of the histidine microenvironments in a human salivary proline-rich glycoprotein. Int. J. Pept. Prot. Res., 32:123-129, 1988

Clark, W.B., Beem, J.E., Nesbitt, W.E., Cisar, J.O.,Tseng , C.C., Levine, M,J. Pellicle receptors for Actinomyces viscosus type 1 fimbriae in vitro. Inf. Imm., 57:3003-3008, 1989.

Tseng, C.C., Scannapieco, F.A., Levine, M.J. Use of a replica-plate assay for the rapid assessment of salivary protein-bacterial interactions. Oral Microbiol. Immunol., 7:53-56, 1992.

Ramasubbu, N., Weaver, T., Tseng, C.C., Bobek, L.A. Levine, M.J. Preliminary X-ray crystallographic analysis of human salivary cystatin. Acta Cryst., D52:869-870, 1996.

Tseng, C.C., Miyamoto, M., Ramalingam, K., Hemavathy, K.C., Levine, M.J., and Ramasubbu, N. The roles of histidine residues at the starch binding site in Streptococcal-binding activities of human salivary alfa-amylase. Arch. Oral Biol. 44:119-127, 1999.

Tseng, C.C., Tseng, C.P., Levine, M.J., and Bobek, L.A. Differential effect toward inhibition of papain and cathepsin C by
recombinant human salivary cystatin SN and its variants produced by a baculovirus system. Arch. Biochem. &
Biophys. 380: 133-40, 2000.

Tseng, C.C., and Tseng, C.P. Identification of a novel secretory leukocyte protease inhibitor-binding protein involved in
membrane phospholipid movement. FEBS Letters. 475: 232-6, 2000.



 

Tetracyclines and Bone Cell Metabolism


Anthony T. Vernillo
Professor of Basic Sciences (Oral Medicine and Pathology).
_________________________________________________________________

1972 B.A.             New York University
1977 D.D.S.        Case Western Reserve University
1982 Ph.D.           The University of Chicago
1982-84 Postdoc Yale University Medical School
1984-                   New York University College of Dentistry, Dept. of Oral Pathology
 ________________________________________________________________

Studies in our laboratory focus on the effects of tetracyclines (TCs) and their nonantimicrobial chemically-modified analogs (CMTs) as potent inhibitors of bone resorption. The inhibitory effects of TCs and CMTs on extracellular pathways for transcription and synthesis of the connective tissue degrading MMPs (collagenase, gelatinase) will be examined with TCs/CMTs in osteoblasts and osteoclasts. Non-enzymatic parameters of osteoclast function will also be studied. Methodologies will include Northern Blot analyses, immunoprecipitation and ELISA, immunocytochemistry and in vitro bone resorption assays. Intracellular calcium concentration in osteoclasts (the principal bone resorbing cells) will be measured using microspectrofluorimetric techniques. Further studies will examine the effects of TCs/CMTs on osteoporosis in animal model systems.
 

Relevant Publications:

Ramamurthy, N.S., Vernillo, A.T., Greenwald, R., Lee, H.M., Sorsa, T., Golub, L.M., Rifkin, B.R. Reactive oxygen species activate and tetracyclines inhibit rat osteoblast collagenase. J. Bone Miner. Res., 8:1247-1253, 1993.

Rifkin, B.R., Vernillo, A.T., Golub, L.M. Blocking periodontal disease progression by inhibiting tissue-destructive enzymes; a potential therapeutic role for tetracyclines and their chemically-modified analogs. J. Periodont., 64:819-827, 1993.

Vernillo, A.T., Ramamurthy, N.S., Golub, L.M., Rifkin, B.R. The nonantimicrobial properties of tetracycline for the treatment of periodontal disease. Curr. Opin. Periodontol., 2:111-118, 1994.

Vernillo, A.T., Rifkin, B.R. Collagenase and other osteoblast enzymes. In: Advances in Organ Biology. Editor, M. Zaidi, JAI Press Inc., Greenwich, CT, pp. 467-482.

Sorsa, T., Ramamurthy, N.S., Vernillo, A.T., Zhang, X., Konttinen, Y.T., Rifkin, B.R., Golub, L.M. Functional sites of chemically-modified tetracyclines (CMTs): inhibition of the oxidative activation of human neutrophil and chicken osteoclast promatrix-metallo proteinases. J. Rheumatol., 25:975-982,1998.

Vernillo, A.T., Rifkin, B.R. Effects of tetracyclines on bone metabolism. Adv. Dent. Res., 12:56-62, 1998.

Ibsen, O.A.C., Phelan, J.A., Vernillo, A.T. Oral manifestations of systemic disease. In: Oral Pathology for the Dental Hygienist.(Ibsen, O.A.C., Phelan, J. Eds.). W.B. Saunders Co., Philadelphia. Third Ed.. 2000.
 

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