William J. Grimes
Professor of Biochemistry, and Molecular & Cellular Biology
Ph.D. 1969, University of Colorado

Structures and functions of molecules of the immune system; the adoptive immunotherapy of cancer

Web Site: Personal Home Page

Research Interests

My laboratory and research efforts include studies on the immune response in patients with cancer and AIDS, and the development of multimedia exercises for promoting education in the life sciences. Our educational projects involve creating interactive tutorials that use the World Wide Web in providing student support in learning to solve experimental problems as a way of enhancing the educational experience. We have also published a laboratory on AIDS http://www.blc.arizona.edu./aids/) for students from middle school through college that has been very successful in producing a basic understanding of the spread of HIV, demonstrating the scientific methods for detecting the presence of the virus, and forcing students to face the realities of dealing with the threat of AIDS.

My major research efforts represent a collaboration between myself and Dr. Marjorie Smith in the Department of Biochemistry and Dr. Evan Hersch, Dr. Kit Lam, and Dr. Douglas Lake of the Arizona Cancer Center. Our projects are divided into two major areas. First, we have developed methods allowing the stimulation and growth of B-lymphocytes from peripheral blood, lymph nodes, and tumors of individuals with cancer. We have shown that infiltrating B-lymphocytes make antibody that reacts with cancer cells from the patient, and also with tumors of the same histological type from other patients. We are using PCR and molecular cloning techniques to amplify and clone the antibody genes from patient B-cells. These experiments allow study of the biology of recognized tumor antigens and also produce antibodies for clinical use.

We have also developed methods for studying peptides which are capable of binding to human class I histocompatibility proteins. These systems use random peptide libraries and measure the ability of a peptide to generate a complex between isolated class I proteins and Beta-2 microglobulin. We are studying the specificity's of various human MHC alleles by PCR amplification and insect cell expression of the protein with mapping peptide specificities expressed in a bead library. Dr. Lake has cloned the T-cell receptor (TCR) for the recognition of melanoma antigens, and we are intending studies on the in vitro parameters of binding between MHC, peptide, and TCR. Using T-cells that have infiltrated tumors or from the peripheral blood of HIV infected individuals, we hope to determine the nature of the antigens detected, and develop modified peptides for augmenting and inhibiting the immune response.

Recent Publications

Punt, C.J.A., J.A.M. Barbuto, H. Zhang, W.J. Grimes, K.D. Hatch, and E.M. Hersh. 1994. Antitumor antibody produced by human tumor- infiltrating and peripheral blood B lymphocytes. Cancer Immunol. Immunotherap. 38:225-231.

Smith, M.H., K.S. Lam, E.M. Hersh, M. Lebl and W.J. Grimes. 1994. Peptide sequences binding to MHC class I proteins. Molecular Imm. 31:1431-1437.

Barbuto, J.A., W.J. Grimes and E.M. Hersh. 1995. Antibodies TNF: A component of Beta-cell immune responses with a role in tumor-host interaction. Cancer Immunol. Immunotherapy 40:31-36.

Zhang, H., D.F. Lake, JA Barbuto, R.M. Bernstein, W.J. Grimes and E.M. Hersh. 1995. A human monoclonal anti-melanoma single chain Fv(scFv) antibody derived from tumor infiltrating lymphocytes. Cancer Research 55:3584-3591.

Grimes, W.J., L. Chambers, K.M. Kubo and M.L. Narro. 1996. A laboratory experience simulating transmission of a viral disease (AIDS) detected by a modified ELISA reaction. (submitted).

Grimes, W., E. Willott, M. Lapointe and J. Katcher. 2001. Honors biology on Thursday evenings. The Natl. Honors Reports 22: 20-23.

Contact Information

Mailing:
Dr. William J. Grimes, Professor
Department of Biochemistry & Molecular Biophysics
University of Arizona
1041 E. Lowell Street
Biosciences West #342
Tucson AZ 85721-0088

Telephone: (520)621-5431/-5432
Fax: 520-621-9288

wjgrimes@u.arizona.edu

Biological Sciences West
1041 East Lowell Street
P.O. Box 210088 · Tucson, AZ 85721-0088
Tel: (520) 621-5110
FAX (520) 626-9204

Life Sciences South
1007 East Lowell Street
P.O. Box 210106 · Tucson, AZ 85721-0106
FAX (520) 621-3709