Scripps Research Joint Appointments

Department of Cell and Molecular Biology
The Skaggs Institute for Chemical Biology
Professor, Department of Integrative Structural and Computational Biology
Faculty, Kellogg School of Science and Technology

Research Focus

Studies at the Interface of Molecular Biology, Chemistry, and Medicine

Our laboratory is concerned with problems in molecular biology, chemistry and medicine. Many of our studies involve learning nature's strategies, improving upon them, or inventing new approaches to prepare novel proteins and small molecules that perform specific functional tasks like regulating a gene, destroying cancer, or catalyzing a reaction with enzyme-like efficiency.

A major focus of our laboratory is the design, optimization, and utilization of transcription factors for the directed regulation of gene expression. To accomplish this, our group has developed zinc finger protein based transcription factors as a robust technology for endogenous gene regulation. We are applying this approach to provide transcription-based solutions to disease, to study protein-DNA interactions, and to discover the function of novel genes. This approach allows scientists for the first time to directly regulate endogenous genes.

Our work on catalytic antibodies has focused on molecular programming of complex reaction mechanisms into antibodies. We have shown that our approaches can yield highly effective antibody enzymes that compete with nature's own. We have used these catalysts in asymmetric synthesis and have developed novel chemotherapies based on prodrug activation. These studies have yielded promising results in animal models of cancer and also led to our development of new organocatalytic approaches to asymmetric catalysis with small organic molecules. We discovered that proline and other amino acid derivatives can be used for the rapid and efficient synthesis of a wide-variety of asymmetric molecules that are key in pharmaceutical synthesis. We continue to invent novel organic reactions based on this approach.

The third focus of our laboratory is the development of new immunotherapeutic approaches to disease. To accomplish this, our group developed phage display methods for the selection and in vitro evolution of antibodies. We have applied these to viral diseases and our current efforts focus on creating new genetic and chemical approaches to immunotherapy that include developing novel chemotherapeutics, small molecules that function in concert with antibodies, and gene therapy approaches that use intracellular antibodies. We are applying these methods to create effective therapies for breast and ovarian cancer, melanoma, and AIDS.

Education

Ph.D., Organic Chemistry, Texas A&M University, 1989
B.S., Chemistry and Physics (double major) with honors, Eckerd College, 1985

Professional Experience

2000-present  Kellogg Professor, The Scripps Research Institute, Department of Molecular Biology and Chemistry
1997-present  Janet and W. Keith Kellogg II Endowed Chair in Molecular Biology
1992-present  Director, Cold Spring Harbor Laboratory Annual Fall Course on "Phage Display Of Proteins & Peptides"
1995-2000     Associate Professor, The Scripps Research Institute, Department of Molecular Biology
1991-1995     Assistant Professor, The Scripps Research Institute, Department of Molecular Biology
1989-1991     Postdoctoral Fellow, The Scripps Research Institute and the Pennsylvania State University

Awards & Professional Activities

Co-recipient of the 2000 Presidential Green Chemistry Challenge Award
Janet and W. Keith Kellogg II Endowed Chair in Molecular Biology
Investigator Award, Cancer Research Institute
Scholar of The American Foundation for AIDS Research
Fellow, American Association for the Advancement of Science
ISI Highly Cited Researcher
Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry
ACS Cope Scholar Award
NIH Director's Pioneer Award
Co-Founder, Prolifaron Inc.
Founder, CovX Pharmaceuticals
Founder, Zyngenia Inc.

Selected References

Beerli, R.R.; Barbas III, C.F. Engineering Polydactyl Zinc Finger Transcription Factors. Nature Biotechnology, 20(2):135,2002.

Shabat,D.; Lode,H.N.; Pertl, U.; Reisfeld, R.A.; Rader, C.; Lerner, R.A.; Barbas, III, C.F. In vivo activity in a catalytic antibody-prodrug system: antibody catalyzed etoposide prodrug activation for selective chemotherapy. Proc. Natl. Acad. Sci., USA 98(13):7528, 2001.

Notz, W.; Tanaka, F.; Barbas III, C.F. Enamine-based organocatalysis with proline and diamines: The development of Direct Catalytic Asymmetric Aldol, Mannich, Michael, and Diels-Alder Reactions. Acct. Chem. Res., 37(8):580-591. 2004

Rader, C; Sinha, S.C.; Popkov, M.; Lerner, R.A.; Barbas III, C.F. Chemically programmed monoclonal antibodies for cancer therapy: Adaptor immunotherapy based on a covalent antibody catalyst. Proc. Nat. Acad. Sci., USA, 100(9):5396-5400. 2003

Dr. Barbas' publications can be found on the Barbas Lab webpage at http://www.scripps.edu/mb/barbas/

Links

The Skaggs Institute Scientific Report

The Skaggs Institute for Chemical Biology

Catalysis Made Easy

Designer Zinc Finger Proteins

Software for the Genome

Towards Novel DNA Enzymes

Barbas Lab webpage