MIT Reports to the President 1997-98
This is the final Report to the President concerning an independent Division of Toxicology. Earlier this year the Division moved administratively from Whitaker College of Health Sciences and Technology to the School of Engineering, and as of July 1, 1998 we merged with faculty in the School of Engineering and the Whitehead Institute into a new Division of Bioengineering and Environmental Health. It is anticipated that these moves will strengthen an already outstanding program through the development of new resources and new educational and research opportunities. The Ph.D./S.M. degree programs in toxicology will be conserved, and an important new role will be opened for introduction of toxicological principles into the undergraduate curriculum. This will be accomplished both through the introduction of "modules" into existing courses, and through the development of an undergraduate minor in Environmental Health.
The Division of Toxicology's 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, Bevin Engelward, John M. Essigmann, James G. Fox, Ram Sasisekharan, David B. Schauer, James Sherley, Steven R. Tannenbaum, William G. Thilly, and Gerald N. Wogan. James G. Fox is also Director of the Division of Comparative Medicine. Professors Essigmann, Tannenbaum and Wogan hold joint appointments in the Department of Chemistry; Professor Thilly also serves as Director of the Center for Environmental Health Sciences. Professor Dedon was promoted to Associate Professor with Tenure.
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 the 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.
In 1997-8 there were 3 students enrolled in the S.M. program and 31 in the Ph.D. program. Degrees awarded included 1 S.M. and 6 Ph.D.'s
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 M.I.T. 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 M.I.T. Minority Summer Science Research Program (MITSSRP). This program was initiated in 1986 as an institutional effort to address the issue of under-representation 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 M.I.T. 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. This has proven to be an effective recruitment path, as approximately one-half of our current and formerly enrolled minority doctoral candidates were Summer Program interns before joining the Division. This year two interns are in our Division, one with Professor Dedon and one with Professor Schauer.
Two new minority students joined the Division in Fall, 1997. Cecilia Fernandez earned the B.A. Degree in biology from Boston University and Jose Marquez was an undergraduate in Civil & Environmental Engineering at M.I.T. In addition, there are three continuing students. Pablo Herrero was an undergraduate in Chemical Engineering at M.I.T. before joining the Division. Curtis Glover earned his B.S. degree in chemistry and biology at Cheney University of Pennsylvania. Jacquin Niles earned the S.B. degree in Chemistry at M.I.T. and is enrolled in the Toxicology Ph.D. program which he will complete in conjunction with the M.D./Ph.D. program at Harvard Medical School.
Efforts to recruit members of underrepresented minorities into the Toxicology program are being conducted in coordination with institutional programs with similar objectives within M.I.T. For example, the Division is one of four academic units at M.I.T. participating in the Sloan Foundation Fellowship program which provides financial assistance to support the recruitment and funding of new minority graduate students. Both of our incoming new students, Ms. Fernandez and Mr. Marquez, were supported as Sloan Foundation Fellows during their first year of graduate study. These efforts have been developed with the support of and in consultation with Isaac M. Colbert, Senior Associate Dean of the Graduate School.
HONORS AND AWARDS
The following honors and awards were accorded to faculty and students of the Division during the current academic year.
Ms. Sophie Currier was awarded an Ida Green Fellowship. Ms Currier is an S.M. candidate in Prof. John M. Essigmann's lab.
Professor Bevin Engelward was appointed to the Samuel A. Goldblith Development Professorship.
Professor John M. Essigmann won the Arthur C. Smith Award which was established in 1996 on the occasion of Dean Smith's retirement from the position of Dean for Undergraduate Education and Student Affairs. The award honors the service of Dean Smith and is presented to a member of the MIT faculty for meaningful contributions and devotion to undergraduate student life at MIT.
Ms. Cecilia Fernandez, a doctoral candidate in Toxicology who is conducting her thesis research with Prof. Bevin Engelward and Mr. Jose Marquez, a Master's candidate with Prof. William G. Thilly, were awarded Sloan Fellowships for the 1997-1998 academic year. Ms Fernandez has been awarded the three-year Ford Foundation fellowship for Minorities beginning September, 1998.
Professor James G. Fox received the Merit Award for Research in Comparative Medicine from the Massachusetts Veterinary Medical Association, and was appointed to the Editorial Board of the new journal Helicobacter.
Ms. Maria Kartalou of the Essigmann lab has been selected by the Graduate Education office for the Henry Bromfield Rogers Fellowship which provides tuition and stipend for the Fall '98 term.
Ms. Carrie Pesce, who completed her first year of graduate work in Prof. Bevin Engelward's lab, has been awarded a five year D.O.D. National Defense Science and Engineering Fellowship which begins September of 1998.
Mr. Zachary Shriver, a student in Prof. Sasisekharan's group, has been awarded the prestigious Whitaker Health Sciences Fund Fellowship for 1998-99.
Professor William G. Thilly was elected to the presidency of two national organizations representing environmental health scientists: the Association of University Environmental Health Sciences Centers and the Association of Superfund Universities. In these capacities he continues to organize presentations in many states and districts regarding the needs of university researchers trying to provide a scientific basis for decision making in environmental, food and drug regulatory practice.
Ms. Aoy Tomita was one of two recipients honored with the Poitras Fellowship for graduate students conducting research in the biomedical sciences.
Professor Gerald N. Wogan received a Fogarty Scholar-in-Residence Award from the National Institutes of Health, which extends over the 1997-1999 period. It is an award supporting scholars from all over the world to work at NIH in order to stimulate development of new research initiatives for the NIH and also to foster collaborative research endeavors among and with NIH scientists.
Mr. Jinghai Xu, a doctoral candidate in Toxicology working with Prof. Peter C. Dedon was awarded the Whitaker Health Sciences Fellowship.
TEACHING AND RESEARCH
Professor Peter C. Dedon has made important advances in both teaching and research in the past year. With regard to teaching, he spearheaded the development of an undergraudate minor in environmental health and Toxicology, which has been designed to appeal to a braod spectrum of science and engineering majors. Two new courses have been developed as part of this minor: Introduction to Physiological Modeling, taught by Profs. Sasiskharan and Lauffenberger; and Infectious Agents and the environment, taught by Prof. Schauer. Following the first offering of these new courses, we will petition for approval of the Minor for the Fall of 1999.
Professor Dedon has also made several important research discoveries in the past year. One addresses the biologically important phenomenon of DNA supercoiling and how supercoiling determines the location of DNA damage in the genome. Using a technique developed in his laboratory to prepare positively supercoiled DNA, his research group discovered that positive supercoiling caused heretofore undescribed changes in DNA structure and dynamics that significantly affect the interaction of the DNA with even the most reactive genotoxins. On a second front, Prof. Dedon discovered that products derived from oxidation of deoxyribose in DNA, namely base propenal, react with DNA bases to produce mutagenic lesions. Prof. Dedon is now extending these studies to several other electrophilic products of DNA oxidation as well as an abundance of potentially reactive intermediates of cellular metabolism. These results have opened up a new area of genetic toxicology that may account for a significant portion of so-called "spontaneous" DNA damage and mutation.
Professor Bevin Engelward's research is on the recombination of DNA and how it is known to contribute to tumorigenesis, since recombination events can results in loss of genetic information. Somatic recombination in human cells is known to be stimulated by DNA damage. Whilst it is clear that double strand breaks are highly recombinogenic, it is less clear how lesions that affect only one strand of duplex DNA stimulate recombination. Her group has recently shown that removal of alkylation damage by base excision repair enzymes prevents mutagenic recombination in S. cerevisiae. These are the first studies show that repair of alkylation damage by this repair pathway suppresses mutagenic recombination. They now directing their efforts toward understanding the molecular basis for the ability of alkylation lesions to stimulate recombination. In addition, they are developing tools for studying the role of various DNA repair processes in preventing somatic recombination events that may lead to cancer. They expect the work that is underway to help us understand why some people are more susceptible to cancer than others. In addition, many cancer chemotherapeutics induce recombination, and these recombination events may contribute to secondary tumors induced by exposure to the anticancer drug itself. By understanding the basis chemotherapy induced recombination, it may become possible to design better anticancer drugs with reduced side effects.
Professor David Schauer's research accomplishments have to do with the etiology of inflammatory bowel disease. Human inflammatory bowel disease has no known cause. He has now shown in three distinct mouse models of inflammatory bowel disease that infection with pathogenic bacteria of the genus Helicobacter cause disease expression. He has also successfully performed genetic manipulation of these murine Helicobacter species. This had not been accomplished previously, and will allow his group to define the molecular basis of disease induction by these pathogens.
In the Thilly laboratory, the technical ability to measure point mutations in human mitochondrial or nuclear DNA has achieved its long term goal of measuring mutations directly in human organs. The first published papers reveal that mitochondrial mutations arise from endogenous processes such as reaction with chemicals manufactured by cells themselves or errors in DNA replication. The study of nuclear sequences, technically more challenging, is underway. These data represent a significant challenge to the widely held belief that environmental conditions associated with cancer, such as cigarette smoking, act via direct induction of mutations through chemical reaction products in DNA.
More information about the Division of Toxicology can be found on the World Wide Web at the following URL: http://web.mit.edu/tox/www/
Steven R. Tannenbaum
MIT Reports to the President 1997-98