MIT Reports to the President 1995-96


The Division of Toxicology is an academic unit of the Whitaker College of Health Sciences and Technology. Its major educational activity is the operation of a graduate degree program leading to S.M./Ph.D. degrees in toxicology. Teaching as well as research programs emphasize mechanisms through which chemical and physical agents in the environment induce toxicity and pathogenesis.

The objective of the programs of the Division is to train scientists who will be professionally qualified to make research contributions to improve understanding of the impacts of hazardous chemicals and other environmental agents on human health, and to educate future generations of scientists with similar interests and qualifications. Special emphasis is placed on development and application of in vivo and in vitro experimental models and approaches designed ultimately to elucidate, in cellular and molecular terms, mechanisms through which such agents induce their adverse effects. Strong emphasis is placed on the development, validation and application of methodology for detection and characterization of adverse effects that will improve assessment of hazards to humans resulting from environmental exposures. Utilizing biochemical, chemical and biological approaches, the training of pre- and post-doctoral trainees is concerned with: characterization of effects of toxic, carcinogenic and mutagenic chemicals at intact animal, tissue, cellular and molecular levels; development of methods for the detection and quantification of such effects in humans, experimental animals, and other experimental systems; studies of metabolic activation, macromolecular binding and genetic effects; and elucidation of modes of action at cellular and molecular levels.


Faculty members whose primary academic affiliations are in the Division include Professors Peter C. Dedon, John M. Essigmann, Steven R. Tannenbaum, Ram Sasisekharan, David B. Schauer, William G. Thilly, and Gerald N. Wogan. Dr. James G. Fox, director of the Division of Comparative Medicine also is a Professor in the Division of Toxicology. Professors Essigmann, Tannenbaum and Wogan hold joint appointments in the Department of Chemistry. Professor Thilly also serves as Director, and other Toxicology faculty form the nucleus of the Center for Environmental Health Sciences in Whitaker College of Health Sciences and Technology.


The Division offers a graduate degree program leading to PhD or SM degrees in Toxicology. The curriculum is designed to provide rigorous training in basic sciences, with particular emphasis on graduate subjects in biochemistry, molecular biology and genetics as well as toxicology. Graduates of the doctoral program follow career paths in academic, industrial or governmental organizations requiring applications of modern methods of chemical, molecular biological and genetic analysis to research related to evaluation of risks associated with chemical exposures. The scope of both educational and research programs encompasses subject matter pertinent to activities of chemical, biotechnology, pharmaceutical, and food industries, as well as to governmental regulatory and research agencies.

Students admitted into the degree program pursue a series of required and elective subjects that ordinarily require three semesters to complete. Following successful completion of comprehensive written and oral examinations, usually administered in the fourth term of study, students must submit and defend a thesis proposal not later than three semesters later. Thesis committees are comprised of three to five faculty members from the Division of Toxicology as well as other departments of MIT, Harvard or other institutions as required by the nature of the doctoral thesis research.


Specific efforts to recruit members of underrepresented minority groups are made at several levels. In the context of general recruiting efforts, all notices and other documents clearly state the MIT and program commitment to recruitment of minority candidates. Additional recruiting efforts include internships, faculty visits, conferences, mailings and informal networking by current minority trainees.

An important and most fruitful avenue of contact with prospective minority students has been through the MIT Minority Summer Science Research Program (MITSSRP). This program was initiated in 1986 as an institutional effort to address the issue of underrepresentation of African Americans, Hispanics, and Native Americans in mathematics and the physical and biological sciences in the United States. The Summer Science Program is designed to provide opportunities for talented minority sophomores and juniors to spend a summer on the MIT campus working in an active research program under the guidance of faculty, postdoctoral fellows, and graduate students. The Toxicology faculty have consistently been active participants in the MITSSRP since its inception; during the summer of 1995, four Toxicology faculty sponsored interns. This has proven to be an effective recruitment path, as four of our currently enrolled minority doctoral candidates were Summer Program interns before joining the Division. Three of seven students admitted for the 1995-96 academic year were members of under-represented minority groups, and two of the three were MITSSRP interns in the summer of 1994. The Summer Science Program interns receive advice and information about graduate study directly from their Faculty Sponsors, laboratory supervisors and the Division Academic Administrator.

Toxicology faculty are also involved in minority recruitment activities outside of MIT. At approximately annual intervals, at least one faculty member personally visits campuses of colleges that enroll large numbers of minority students in order to meet with prospective applicants and to develop contacts with faculty members of science departments. Toxicology students have represented our graduate program at several schools and meetings, including the annual Minority Access to Research Careers (MARC) and Ford Fellows meetings.

The following minority students are currently enrolled as doctoral candidates in the Division. LaCreis Kidd and Deirdre Lawrence both received their undergraduate training in Biology at Spelman College. Curtis Glover received his BS degree in chemistry and biology at Cheney University. J. Cristopher Goodwin received his BS degree in biology at the University of Maryland Baltimore Campus. Ms. Kidd and Ms. Lawrence have passed the doctoral examinations and are nearing completion of their thesis research projects.

Several minority students received degrees in June, 1996. Donald Brunson was awarded the PhD degree, and has entered a postdoctoral fellowship at the Johns Hopkins University School of Public Health. Paula Lee was awarded the SM degree in Toxicology, and will enter the MD program at Baylor University. Esequiel Barrera received the SM degree and is employed as Assistant Biosafety Officer at MIT.

Efforts to recruit members of underrepresented minorities into the Toxicology program are being conducted in coordination with institutional programs with similar objectives within MIT. Current efforts as well as those proposed for the future have been developed with the support of and in consultation with Isaac M. Colbert, Senior Associate Dean and Margaret D. Tyler, Associate Dean of the Graduate School of MIT for minority student affairs.


Two new faculty members were identified through a national search as candidates for appointment as faculty members in the Division during the past year. Dr. Ram Sasisekharan was appointed Assistant Professor effective July 1, 1996, and Dr. Bevin Engelward was appointed Assistant Professor, to become effective September 1, 1997.

Dr. Ram Sasisekharan received his BS degree in physical sciences from Bangalore University, his MS degree in biophysics from Harvard University and his PhD in medical sciences from Harvard Medical School. After completion of his doctorate, he was Instructor in Biology at MIT, and Research Associate in the Division of Health Sciences and Technology. He is a well-rounded scientist with an excellent background in molecular pharmacology, cell biology, protein biochemistry, sustained release delivery together with a high level of sophistication in molecular modeling.

Dr. Sasisekharan's research accomplishments to date are outstanding. The objective of his doctoral thesis was the cloning, expression and regulation of the gene for heparinase, the enzyme that degrades heparin and inactivates its anticoagulant activity. He was the first to clone and expressing the gene in several systems, succeeding where many previous investigators failed to do so in other laboratories. More recently, he has shown that heparinase can be used to prevent neovascularization, leading to studies on its ability to release cytokines from the intercellular matrix. An outcome of this work was the elucidation of the molecular mechanism by which heparin and fibroblast growth factor interact to cause receptor binding and cell signaling. These are highly significant accomplishments, given the growing realization of the importance of heparin and heparin sulfate proteoglycan in biological processes, for example in growth factor action, matrix biology and smooth muscle proliferation. Sasisekharan's work makes possible analysis of structural interactions of carbohydrates and proteins, as well as characterization of heparin-binding proteins, and thus has the potential to make major contributions to both basic and clinical research. Importantly, his program will provide a substantive and dynamic link with other programs in Whitaker College including HST, the Center for Biomedical Engineering and the Center for Experimental Therapeutics.

Dr. Bevin Engelward received her BA degree from Yale University. She conducted her doctoral thesis research in the laboratory of Prof. Leona D. Samson in the Department of Molecular and Cellular Toxicology at the Harvard School of Public Health, where she was awarded her PhD degree in June, 1996. As a graduate student, she received predoctoral fellowships from the Society of Toxicology and the Pharmaceutical Manufacturer's Association, both highly competitive, peer-reviewed awards. Her educational background has provided her with excellent backgrounds in biochemistry as well as molecular and cellular toxicology, and her area of research is of particular relevance to continued development of the programs of the Division of Toxicology.

Her research interests focus on responses of mammalian cells to the DNA damage induced by alkylating agents, many of which are mutagens, carcinogens and anticancer agents. Most of the compounds she studies are widely distributed in the environment and are also produced endogenously. Others are frequently used in patients being treated for cancers. The biological consequences of different types of alkylation lesions in DNA vary dependent on their specific structure. Some are innocuous, while others are potent mutagens or are lethal to cells if they are not repaired. Engelward's research concerns elucidation of DNA repair processes and their role in mutagenesis and lethality of alkylating agents. She identified a thesis topic that was both demanding and of great potential impact on the DNA repair field. The initial objective was to clone and characterize a mammalian 3-methyladenine DNA glycosylase cDNA (Aag), then to use the cloned gene for targeted homologous recombination in order to develop mutant mammalian cells deficient in DNA repair activity. No such cells had previously been developed, and their availability would provide powerful tools with which to characterize this aspect of DNA repair under in vivo conditions. She was spectacularly successful in accomplishing both objectives, the cloning being achieved using established methodology, and the targeted recombination using mouse embryonic stem cells and novel procedures that she developed independently. The mutant cells produced are currently being used to develop transgenic mice that will bear a homozygous null mutation in the Aag gene. If they are viable, they will provide a unique tool for exploring this repair activity in intact animals. The multidisciplinary strategy she employed in developing this project brings great strength to a field that has tended to be overcompartmentalized and represents a useful model for future work.


The following honors and awards were accorded to faculty and students of the Division during the current academic year.

Prof. John M. Essigmann was the recipient of the 1996 School of Science Teaching Prize for Excellence in Undergraduate Teaching. Prof. Essigmann received this accolade on the basis of his outstanding teaching in 5.07, which he also developed as a new course offering in 1992.

Mr. William Kobertz, a doctoral candidate in Organic Chemistry conducting his thesis research in the laboratories of Prof. John Essigmann and Prof. Gerald Wogan received the American Chemical Society Division of Medicinal Chemistry Fellowship supported by the Abbott Corporation.

Mr. Jinghai Xu, a doctoral candidate in Toxicology working with Prof. Peter C. Dedon was awarded the Whitaker Health Sciences Fellowship, which is awarded to one doctoral student in Life Sciences or Bioengineering annually.

Mr. Curtis Glover, a doctoral candidate in Toxicology who is conducting his thesis research with Prof. William G. Thilly, was awarded a Sloan Fellowship for the 1995-1996 academic year. These fellowships are intended to provide support for minority students, and are competitively awarded by Dean Isaac Colbert, of the Graduate Education Office.

Ms. Laura Kennedy, a candidate for the SM degree in Toxicology working with Prof. Steven R. Tannenbaum, was the recipient of a PEEER Martin Fellowship from the Programs for Environmental Engineering Education and Research, awarded by the PEEER Steering Committee.


Prof. Steven R. Tannenbaum has been appointed Director of the Division of Toxicology, effective September 1, 1996. He will replace Prof. Gerald N. Wogan, who will return to research.

Gerald N. Wogan

MIT Reports to the President 1995-96