Robert Ladner PhD.

Office:

Education:

1986-1990: Saint Joseph's University, B.S. (Biology)

1990-1992: Rutgers University, M.S. (Biology)

1992-1996: Rutgers University/UMDNJ, Ph.D. (Cell and Developmental Biology)

Thesis:

M.S. 1992: Characterization of Mitochondrial DNA from the Marine Dinoflagellate Crypthecodinium cohnii.

Ph.D. 1996: Biochemical Characterization of Human Deoxyuridine Triphosphate Nucleotidohydrolases.

University Appointments

Awards & Honors:

1991: Best student presentation award, New Jersey Academy of Science Annual Meeting.

1991: Scholarship to attend the Molecular Marine Ecology summer course at the Marine Biological Laboratory, Woods Hole, Massachusetts.

1992: Rutgers University Alumni Award for Academic Excellence.

1995: Outstanding Poster Award, AACR Annual Meeting, Toronto.

1996: Scholarship to attend the American Association for Cancer Research Workshop: Histopathobiology of Neoplasia, Keystone, Colorado.

Committee Responsibilities:

1999 - Present / GSBS Admissions Committee

1998 - Present / SOM Curriculum Committee

1998 / IACUC Committee

Memberships:

American Association for Cancer Research

Major Research Interests:

Development and validation of molecular targets for cancer chemotherapeutic drug development. Development of prognostic markers for overall survival and tumor response to chemotherapy in gastrointestinal cancers.

Research and Teaching Experience:

UMDNJ-SOM

1998 - Present Course Director, Histology

1997 - Present Lecturer - Immune system and Endocrine glands Lab Director - Coordination and lecturing of all laboratory sessions for Histology

UMDNJ-GSBS

1996 - Present Lecturer, Molecular Biology of the Cell - Protein Function, Mechanics of Cell Division, Cancer Biology 1996 - Present Lecturer, Problems in Molecular Biology - Viral Control of Apoptosis

Research Experience:

1989 (Fall): Conducted student research project during a semester at the Sea Education Association (Woods Hole, MA) involving marine algae aboard the R/V Corwith Cramer. Six week passage from Woods Hole to St. Thomas, USVI.

1989-1990: Undergraduate research at St. Joseph's Univ. in the lab of Dr. Patricia Mancini. Isolation and characterization of surface glycoproteins from Trypanosoma brucei.

1990-1992: Masters degree thesis research at Rutgers University in the lab of Dr. Donald E. Stearns. Characterization of mitochondrial DNA from the marine dinoflagellate Crypthecodinium cohnii.

1991: Attended the Molecular Marine Ecology course at the Marine Biological Laboratory, Woods Hole, MA.

1991-1992: Teaching Assistant, Molecular Biology and Microbiology, Rutgers University, Department of Biology.

1992: Research Consultant, Department of Molecular Biology, UMDNJ.

1993-1996: Doctoral thesis research at the University of Medicine and Dentistry of New Jersey in the lab of Dr. Salvatore J. Caradonna. Biochemical Characterization of Human Deoxyuridine Triphosphate Nucleotidohydrolases.

1996-1997: Post-doctoral research at the University of Medicine and Dentistry of New Jersey in the lab of Dr. Salvatore J. Caradonna. Differential regulation of distinct nuclear and mitochondrial isoforms of human dUTPase.

Students Supervised:

GSBS Catherine Rizzo, Lin Geng, Beverly Mastran-Tinkelenberg

SOM Ariel Meyer, David MacBride

Publications:

Caradonna, S.J., Ladner, R.D., Hansbury, M., Kosciuk, M., Lynch, F. and Muller, S.J. (1996). Affinity purification and comparative analysis of two distinct human uracil-DNA glycosylases. Experimental Cell Research. 222, 345-359.

Marta, P.T., Ladner, R.D.and Grandoni, J.A. (1996). A CUC triplet confers leucine-dependent regulation of the Bacillus subtilus ilv-leu operon. J. Bacteriol. 178, 2150-2153.

Ladner, R.D., McNulty, D.E., Carr, S.A., Roberts, G.D. and Caradonna, S.J. (1996). Characterization of distinct nuclear and mitochondrial forms of human dUTPase. J. Biol. Chem. 271, 7745-7751.

Ladner, R.D., Carr, S.A., Huddleston, M.J., McNulty, D.E. and Caradonna, S.J. (1996). Identification of a consensus cyclin dependent kinase phosphorylation site unique to the nuclear form of human dUTPase. J. Biol. Chem. 271, 7752-7757.

Ladner, R.D. and Caradonna, S.J. (1997). The Human dUTPase gene encodes both nuclear and mitochondrial isoforms: Differential expression of the isoforms and characterization of a cDNA encoding the mitochondrial species. J. Biol. Chem. 272, 19072-19080.

Horowitz, R.W., Zhang, H-Y., Schwartz, E.L., Ladner, R.D., and Wadler, S. (1997). Measurement of deoxyuridine triphosphate and thymidine triphosphate in the extracts of thymidylate synthase-inhibited cells using a modified DNA polymerase assay. Biochem. Pharm. 54, 635-638.

Wadler, S., Damle, S. Haynes, H., Kaleya, R., Schechner, R., Berkenblit, R., Ladner, R.D., and Murgo, A. (1999) Phase II/pharmacodynamic trial of dose-intensive, weekly parenteral hydroxyurea and fluorouracil administered with interferon alfa 2a in patients with refractory malignancies of the gastrointestinal tract. J. Clinical Oncology. 17(6):1771-8.

Webley, S.D., Hardcastle, A., Ladner, R.D., Jackman, A.L. and Aherne, G.W. (2000). Deoxyuridine triphosphatase (dUTPase) expression and sensitivity to the thymidylate synthase (TS) inhibitor ZD9331. Br. J. Cancer. 83(6):792-9.

Ladner, R.D., Lynch, F.J., Groshen, S., Xiong, Y.P. Sherrod, A., Caradonna, S. and Lenz, H-J. (2000) Expression of dUTPase isoforms in normal and neoplastic tissues: Association with survival and response to 5-FU in colorectal cancer. Cancer Res. 60(13):3493-503.

Mastran, B.M., Hansbury, M.J, Meyer, A. and Ladner, R.D. (2000). The Role of Uracil-DNA Metabolism in Thymineless Death (In preparation)

Presentations and Abstracts:

2000: Ladner, R.D., Mastran-Tinkelenberg, B.A. and M.J. Hansbury. Aberrant Uracil-DNA Metabolism Activates Thress Distinct Checkpoints in Saccharomyces cerevisiae. LXV Cold Spring Harbor Symposium, Biological Responses to DNA Damage, Cold Spring Harbor Laboratory, New York.

2000: Ladner, R.D., Mastran-Tinkelenberg, B.A., Meyer, A., Wisniewski, T.J., Geng, L., Muller-Weeks, S., and Henry, M.F. The Role of Uracil-DNA Metabolism in Mediating Antifolate Cytotoxicity in Saccharomyces cerevisiae. 91st Annual Meeting of the American Association for Cancer Research, San Francisco, CA.

2000: Ladner, R.D., Stoehlmacher, J., Lynch, F.J., Wei, D., Xiong, Y.P., Sherrod, A., Caradonna, S.J., and Lenz, H-J. dUTPase Isoform Expression in Normal and Neoplastic Tissues: Association with survival and Response to 5-FU in Colon and Gastric Cancer. 91st Annual Meeting of the American Association for Cancer Research, San Francisco, CA. (oral presentation)

2000: Mastran-Tinkelenberg, B.A., Hansbury, M.J. and Ladner, R.D. The Role of Uracil-DNA Metabolism in Mediating Thymineless Death in Saccharomyces cerevisiae: Implications for Cell Cycle Checkpoint Control. The University of Medicine and Dentistry of New Jersey - School of Osteopathic Medicine, Fourth Annual Research Day

2000: Meyer, A., Mastran-Tinkelenberg, B.A., and Ladner, R.D. The Role of dUTPase and Uracil-DNA Glycosylase in Mediating Antifolate Cytotoxicity in Saccharomyces cerevisiae. The University of Medicine and Dentistry of New Jersey - School of Osteopathic Medicine, Fourth Annual Research Day

2000: David MacBride, D., Mastran-Tinkelenberg, B.A., and Ladner, R.D. A Genetic Screen for Temperature Sensitive Mutants of dUTPase in Saccharomyces cerevisiae. The University of Medicine and Dentistry of New Jersey - School of Osteopathic Medicine, Fourth Annual Research Day

1999: Lenz, H-J, Habashy, M., Xiong, Y-P, Lynch, F., Caradonna, S., Pullarket, S., Tsao-ei, D. and Ladner, R. dUTPase Expression in GI Cancer: Association with Response and Survival. Proc. ASCO 18:970, 1999.

1998: Ladner, R.D. "The Role of dUTPase in Thymidylate Synthase Inhibitor-Based Chemotherapy" Colorectal Cancer Multidisciplinary Conference, Dec. 15,1997 - Thomas Jefferson University Hospital (oral presentation).

1998: Ladner, R.D. "The Role of dUTPase in Thymidylate Synthase Inhibitor-Based Chemotherapy" Presented to the Dept. Of Oncology, Feb. 14,

1998 - USC-Norris Cancer Center (oral presentation). 1997: Ladner, R.D. and Caradonna, S.J. Lowering dUTPase levels through antisense induces sensitivity of fluorodeoxyuridine in HT29 cells. 88th Annual Meeting of the American Association for Cancer Research, San Diego, CA. (oral presentation)

1997: Ladner, R.D., Lynch F.J. and Caradonna, S.J. Differential expression and immunohistochemical localization of human dUTPase isoforms. 88th Annual Meeting of the American Association for Cancer Research, San Diego, CA.

1997: Brown, S.D., Ladner, R.D., Maybaum, J., and Aherne, G.W. Deoxyuridine triphosphate (dUTP) accumulation: Relevance to the cytoxic effects of thymidylate synthase (TS) inhibitors. 88th Annual Meeting of the American Association for Cancer Research, San Diego, CA

1996: Ladner, R.D. and Caradonna, S.J. Differential regulation of distinct nuclear and mitochondrial isoforms of human dUTPase. American Society for Biochemistry and Molecular Biology, DNA Repair Satellite Meeting, New Orleans, LA.

1996: Lynch, F.J., Ladner, R.D., and Caradonna, S.J. Expression of dUTPase in normal and neoplastic human tissues. American Society for Investigative Pathology Annual Meeting, New Orleans, LA.

1995: Ladner, R.D., McNulty, D.E., Carr, S.A. and S.J. Caradonna. Human dUTPase: Physical characterization and identification of a cell cycle dependent kinase phosphorylation site., Toronto, Canada.

1995: Ladner, R.D., McNulty, D.E., Carr, S.A. and S.J. Caradonna. Human dUTPase: Characterization of distinct nuclear and mitochondrial forms. Eukaryotic DNA replication meeting, Cold Spring Harbor Laboratory, NY.

1994: Grandoni, J. and R.D. Ladner. A CUC triplet in the leader region of the Bacillus subtilis ilv-leu operon is required for leucine-dependent regulation. American Society for Microbiology 94th General Meeting, Las Vegas, NV.

1994: Ladner, R.D. and S. Caradonna. Cloning, expression and functional analysis of human dUTPase. American Association of Cancer Research Annual Meeting, San Francisco, CA.

1993: Ladner, R.D. and S. Caradonna. Molecular cloning, functional expression and site directed mutagenesis of a human cDNA encoding deoxyuridine nucleotidohydrolase (dUTPase). Cancer Institute of New Jersey , 1st Annual Scientific Retreat, Piscataway, NJ.

1993: Muller, S.J., R.D. Ladner and S. Caradonna. Association of uracil DNA glycosylase with the proliferating cell nuclear antigen, (PCNA). American Association for Cancer Research (Genetic Control of Cell Growth), Galveston, TX.

1992: Ladner, R.D., D.E. Stearns and M.J. Goldenthal. Partial sequence of the cytochrome c oxidase I gene from the marine dinoflagellate Crypthecodinium cohnii. New Jersey Academy of Science, Trenton, NJ.

1991: Ladner, R.D., D.E. Stearns, C. Beam and M.J. Goldenthal. Isolation and characterization of the mitochondrial DNA from the marine dinoflagellate Crypthecodinium cohnii. American Society for Cell Biology 31st Annual Meeting, Boston, MA.

1991: Ladner, R.D., D.E. Stearns and M.J. Goldenthal. Isolation and restriction mapping of mitochondrial DNA from the marine dinoflagellate Crypthecodinium cohnii. New Jersey Academy of Science, Hoboken, NJ. March 1, 2000