Iwao Ojima, Distinguished Professor
B.S., 1968, The University of Tokyo
M.S., 1970, The University of Tokyo
Ph.D. 1973, The University of Tokyo
Phone: (631) 632-7890
Fax: (631) 632-792
Senior Research Fellow and Group Leader, Sagami Institute for Chemical Research, 1973-1983
Associate Professor (1983), Professor (1984), Leading Professor (1991), Distinguished Professor (1995)
Department of Chemistry, State University of New York at Stony Brook
Synthetic Organic and Medicinal Chemistry at the Biomedical InterfaceDiscovery and development of new and potent anticancer agents, antibacterial agents, anti-inflammatory agents, and various enzyme inhibitors are the major research interests in Dr. Ojima’s laboratory. Integration of all relevant chemistry and biological tools, including computational biology (docking, in silico screening, molecular dynamics), chemical biology (protein expression, enzyme assays, fluorescence labeling), cell biology (cell culture, cytotoxicity assay, fluorescent confocal microscopy, flow cytometry, transmission and scanning electron microscopy), has successfully been realized in this program. Naturally, this research program is promoted in close collaboration with cell biologists, oncologists, microbiologist, pharmacologists, hematologists, toxicologists, etc., as well as the Division of Laboratory Animals Resources for in vivo efficacy evaluations.
Tumor-targeting chemotherapeutic agents. The drug discovery program includes tumor-specific drug delivery systems, “guided molecular missiles” in the fight against cancer. Despite the significant progress in the development of cancer detection, prevention, surgery and therapy, there is still no common cure for this disease. In addition, the long-standing problem of chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Therefore, various “molecularly targeted cancer therapies” have been developed for use in specific cancers, including tumor-targeting drug delivery (TTDD). In general, a TTDD system consists of a tumor recognition moiety and a cytotoxic warhead connected through a “smart” linker to form a conjugate. When a multi-functionalized nanomaterial is used as the vehicle, a “Trojan Horse” approach becomes possible for mass delivery of cytotoxic warheads to maximize the efficacy. The Ojima Laboratory has been making an excellent progress in the novel molecular approaches to the design and discovery of “guided molecular missiles” for tumor-targeting chemotherapy.
Novel antibacterial agents targeting bacterial cell division. The program also includes novel antibacterial agents against drug-resistant tuberculosis, MRSA, VRE and other pathogens. Despite extensive research in the last 40 years, the drugs used to treat these infections are still limited to rather classical antibacterial drugs that target cell wall biosynthesis, nucleic acid synthesis, protein synthesis, etc. Furthermore, the widespread misuse of drugs and poor patient compliance have allowed bacteria to become resistant to drugs by means of their adaptive genetic machinery, leading to multi-drug resistant (MDR) strains of bacteria. Widespread bacterial resistance to existing therapeutics for bacterial infections mentioned above has been a key hurdle for the complete treatment. Therefore, in order to counter attack the adaptive genetic machinery of bacteria, there is a dire need for the identification of novel therapeutic targets. In this context, filamentous temperature sensitive protein Z (FtsZ), an essential bacterial cytokinesis protein, is a highly promising therapeutic target since the disruption of cell division would lead to the inhibition/arrest of bacterial infection. The Ojima Laboratory has discovered novel taxanes and benzimidazoles exhibit high potency against drug-sensitive and drug-resistant tuberculosis through efficient inhibition of FtsZ polymerization, which is crucial for bacterial cell division. The drug discovery efforts have been supported by design and synthesis of novel libraries of compounds and moderately high throughput (HTP) screening as well as rational optimization of the hit compounds.
New and efficient synthetic methodology development. The Ojima Laboratory has been exploring and developing new methodologies, especially based on catalytic organic transformations, including enantioselective processes, cyclohydrocarbonylations and higher order cycloadditions and carbocyclizations, which provide the basis for the efficient syntheses of biologically active substances of medicinal interest, such as those anticancer and antibacterial agents mentioned above. Mechanisms of these reactions are also studied based on spectroscopic methods including advanced NMR techniques, computer-assisted molecular modeling, and X-ray crystallography.
Emmanuel B. Herschberg Award, the American Chemical Society, 2001.
The Chemical Society of Japan Award for Distinguished Achievements, 1999.
American Chemical Society Arthur C. Cope Scholar Award , 1994.
The Chemical Society of Japan 25th National Young Investigator Award, 1976.
Inductee, American Chemical Society Medicinal Chemistry Hall of Fame, 2006
Fellow, American Chemical Society, 2010.
Fellow, New York Academy of Sciences, 2000.
Fellow, American Association for the Advancement of Science, 1997.
Fellow, John S. Guggenheim Foundation, 1995.
William and Florence Catacosinos Professor in Cancer Research, 1994.
Distinguished Professorship, State University of New York, 1995.
Leading Professorship, State University of New York at Stony Brook, 1991.
Henry J. Shine Lecturer, Texas Tech University, 2009.
The Sosnovsky Distinguished Lectureship, University of Wisconsin Milwaukee, 2008.
Ralph A. Raphael Lecturer, University of Glasgow, UK, 2008.
Negishi-Brown Lecturer, Purdue University, 2007.
J. Clarence Karcher Lecturer, The University of Oklahoma, 2003.
FMC Discovery Chemistry Lecturer, FMC Corporation, 2003.
Bristol-Meyers Squibb Distinguished Lecturer, Colorado State University, 2002.
Dr. H. Martin Friedman University Lecturer, Rutgers University, 2001.
Weissberger-Williams Lecturer, Eastman Kodak Co., 1997.
Boehringer-Ingelheim Distinguished Lecturer, Colorado State University, 1997.
George Lesher Lecturer, Rensselaer Polytechnic Institute, 1995.
J. Clarence Karcher Lecturer, The University of Oklahoma, 1992.
National Science Council Lecturer, Taiwan, 1990.
Eli Lilly Lecturer, University of Kansas-Lawrence, 1990.
Senior Editor, Future Medicinal Chemistry (2008-present).
Guest Editor, “Modern Natural Products Chemistry in Drug Discovery”, J. Med. Chem. (2007).
Guest Editor, “Modern Molecular Approaches to Drug Discovery”, Acc. Chem. Res. (2007).
Editorial Advisory Board of Current Topics in Medicinal Chemistry (2002-present).
Editorial Advisory Board of Journal of Organic Chemistry (ACS) (1995-1999).
Editorial Advisory Board of Organometallics (ACS) (1996-1998).
Editorial Board of Journal of Molecular Catalysis (1986-1995).
Advisory Committee/Panel Reviewer: NIH, NSF, DOE.
Chairman, Department of Chemistry, State University of New York at Stony Brook (1997-2003), Director, Institute of Chemical Biology & Drug Discovery (2003-present)