Division of Nutrition

Nutrition and Metabolism Training Program Plan

The Training Program will fund three training slots as described below. The primary goal of this program is to provide an intensive and sustained training experience in preparation for a career in nutrition research. The core component of this program is dedicated to trainees with M.D. and/or Ph.D. or D. Sc. degrees and is formulated essentially independent of clinical training opportunities. While most MD candidates for training in clinical research will enter the training program after completing one year of clinical training (in a Nutrition or related field, e.g. Endocrinology, Cardiology, Gastroenterology, Oncology, or Surgery), opportunities will be available to physicians who apply strictly for research experience with or without clinical experience elsewhere as well as Ph.D.'s or D. Sc.'s applying as post-doctoral training candidates. It is a premise of this program that an individual committed to becoming an independent investigator (see description below of candidate selection) must anticipate that three years of laboratory experience in this program is a minimum period of training necessary for a basic science research project and two years experience is a minimum period necessary for training in clinical research or epidemiology. It is our goal to fund two two-year clinical research slots and one three-year basic science spot through this training program. It is further the premise of this program that offering consistent support through the designated training period (either two years or three years, depending on project, focus and qualifications) is important to promoting the goals of this proposal, most importantly allowing trainees to concentrate maximally on their research.

(a) Clinical and Basic/Translational Research Training Program

The main thrust of this program will to train researchers in clinical/translational research. It is anticipated that MD's will represent about two thirds of the trainees and Ph. D.'s and or D. Sc.'s approximately one third of trainees. The core training program is not predicated on a fixed balance among the three different paths of entry (M.D., M.D.-Ph.D., or D. Sc.'s). In aggregate, three trainees will enter per year, two will remain in training for two years and a third, either a Ph.D. or D.Sc. will remain in training for at least three years. A typical training experience is illustrated in TABLE B.

i. Laboratory/preceptor Selection

The central feature of this training program is a continuous intensive clinical/translational research effort under the primary supervision of an experienced mentor. Trainee laboratory assignment, are made through three mechanisms: 1) For individuals entering from a clinical year in a related field (Endocrinology, Cardiology, Gastroenterology, Oncology or Surgery), commitment to a laboratory mentor is made through serial meetings with the Director throughout the preceding year after trainee discussions with at least four of the program's faculty. Final decisions are made no later than April to allow time for preparatory reading and meetings with the chosen preceptor and establishment of a tailored supervisory group (see above) prior to entering training in July. Final approval of these assignments and plans is contingent on review by the Executive Steering Committee, 2) Among those individuals entering the training program without a preceding clinical year, and from one of the identified feeder programs e.g. a postdoctoral candidate from the Harvard School of Public Health, the MGH Weight Program, the Whitehead Program in Medical and Population Genetics, the MIT Program in Nutritional Biochemistry, the MGH Program in Nutritional Metabolism or the Beth-Israel Deaconess Center in Nutrition Medicine, in most instances the application will be initiated to work with a specific faculty member. Again, a supervisory group is established and an Executive Steering Committee review of training plans is undertaken.

ii. Training Plan

All trainees will be committed to spend a minimum of 80% of their time in direct laboratory research. In addition, on average, trainees will spend 10% of their time in formal courses and didactic sessions. For those trainees in whom some continuity in clinical activity is appropriate, no more than 10% of effort will be directed to clinical work; generally this is limited to a single three hour outpatient clinic/week and attendance at grand rounds and related important clinical conferences. Trainees who have night-call or other primary clinical duties will not be allowed into the program, to insure candidates can focus primarily on their designated research projects. An intensive level of laboratory training will be sustained through the two or three year research fellowship (TABLE B). At the end of either the two or three year period it is anticipated that many trainees including most of those entering with a substantial prior research experience (usually MD-Ph.D., Ph.D. or D. Sc. background) will be qualified to develop transitional support, i.e. K23, Career Development Award.

iii. Interdisciplinary Integration and Coordination.

The investigators participating as faculty have extensive existing collaborative interactions. Although trainees may pursue their laboratory research training within the outlined laboratories throughout the Harvard Medical School Campus and affiliated programs, coordination is ensured by the close involvement of the supervisory group and Executive Steering Committee throughout the training period. In addition, all trainees will participate in a number of core activities that will maintain the strength of their connection to an ultimate career goal in nutrition research, within the mission of the NIDDK, and foster interactions among trainees and faculty. For example, all basic/translational trainees will initiate their research program with a didactic course in molecular biology developed by the basic science faculty of the NIH-centers expressly for its trainees. In addition, all trainees actively participate in joint research seminar series attended by faculty from the various laboratories and a weekly research journal club. Finally, the integral role of basic scientific faculty follows from the existing substantial joint research endeavors between these faculty and those affiliated with other programs at HMS, HSPH and affiliated hospitals within the Harvard system. In addition, a primary strength of the proposed training program is the strength of the clinical research faculty. All clinical trainees will initiate their training with the HSPH summer Clinical Effectiveness Program, designed to familiarize clinical researchers in basic issues of study design, quantitative methods and human research concerns (see Appendix) and will be required to participate in the Issues in Physiologic Investigation Course (see Appendix), offered through the MGH CRP and directed by the PI, Dr. Grinspoon.

iv. Didactic Curriculum

Laboratory research training will be enhanced by the active participation of trainees in a rich program of required didactic courses, seminars and journal club as well as a wealth of optional seminar and training experiences available at both MGH and CH, the Harvard Medical School, Harvard University and MIT. The following will be integral to the program for all trainees:

aa. Course work

The Harvard Clinical Nutrition Research Center and the MGH Digestive Disease grant cores have developed an introductory course directed by Dr. Lee Kaplan and Frederick Ausubel of ten lectures given as a weekly series over a few months of laboratory technique sessions which covers basic concepts of molecular and cellular biology and basic laboratory approaches. In addition, during the first two years of training, trainees will enroll in two appropriate formal courses offered at Harvard Medical School, Harvard University or MIT. A comprehensive list of courses selected for trainees is presented in the Appendix C1.

For clinical researchers, MGH/Brigham and Womens Clinical Research Program is a rich resource with many ideal program and courses for investigators to choose from. Some examples of these courses include: 1) Introduction to Clinical Investigation, 2) Problem-Based Biostatistics , Issues in Physiologic Investigation directed by Dr. Grinspoon, 3) Seminars in Biostatistics for Clinical Investigators, and 4) Scientific Writing, and 5) Genetics in Clinical Investigation (see Appendix). Prior course have included Molecular Genetics and Disease Mechanisms. In addition, given the importance of the IRB, and Human studies issues in clinical research, the CRP offers a lecture series on IRB issues, ranging from the meaning of privacy, the ethics of genetics in clinical research, mandatory education requirements, and other issues (see Appendix). Given the increasing importance of genetic research, the CRP has initiated a lecture series on genomics, which has included a lectures on Genomics and Genetic Epidemiology in the Investigation of Complex Diseases (Dr. Althsuler), Bioinformatic Analysis Using the Internet: A Primer on Using Web-based Tools in Functional Genomics Analysis, and Genetic Analysis of Insulin-like Signaling. Prior courses in Proteomics, Research Applications of Magnetic Resonance and MRI, and MR Imaging of the Heart and Non-invasive Quantification of Heart Function are likely to be repeated and may be of interest to clinical research trainees.

bb. Research journal club

All trainees will be required to participate in a newly created journal club for the proposed Training Grant, exclusively dedicated to rigorous examination of relevant basic and translational research articles related to the field of nutrition. This journal club will occur on a monthly basis, and will be lead by the Program Director, and by Dr. Hadigan, Director of Education and Training, and will be attended by all trainees funded by the grant. Each month, two Program Faculty with specific interests in related fields will attend as guest discussants, for example Dr. Flier and Dr. Crowley would attend a journal club discussing the effects of leptin on neuroendocrine signaling in human models of undernutrition and obesity. Specific attention will be made to bringing diverse faculty together for an interdisciplinary discussion, e.g, on the nutrient regulation of leptin production in adipocytes (Dr. Flier) and potential effects on GnRH signaling (Dr. Crowley) in the example above. Trainees are responsible in rotation for a review of the relevant background material. Articles are selected for their basic importance or illustration of a particular experimental approach. In addition, trainees have the opportunity to attend and participate at their discretion in a variety of other research journal clubs maintained among the large community of investigators and the respective Programs and Divisions of the Trainees and their mentors.

cc. Seminars

A number of active research-oriented seminar series are maintained on a longitudinal basis by the programs outlined within this training grant.

1) Boston Nutrition Center Research Seminars, jointly sponsored by the Boston Obesity Nutrition Research Center and the Harvard Clinical Nutrition Research Center held monthly on Tuesday evenings at the MIT Faculty Club. Examples of such seminars include: Altered Adipocyte Metabolism in the HIV Lipodystrophy Syndrome: A Clinical Perspective (Steven Grinspoon, M.D.), Regulation of Lipid Homeostasis by PPARs (Steven Kliewar, Ph.D.), Fatty Acids and Cholesterol: Partners in Lipid Metabolism and Gene Regulation (Richard Deckelbaum, M.D.) Human Genome Sequence Variation and the Genetics of Common Disease (David Altshuler, M.D.), Nutrition and Bone (Catherine Gordon, M.D.),

2) The HSPH Division of Nutrition Weekly Seminar Series (see Appendix),

3) the HSPH Nutrition Seminar Series, covering a broad range of nutrition topics including, Regulation of Iron Transport in Reticuloendothelial Cells, Characterization of Diet Dependent Metabolic Serotypes, Multivitamins and Perinatal Health Among HIV-Infected Women, The Role of Calcium and Vitamin D in Preserving Bone Health, and Obesity in Developing Countries: The Possible Role of Early Nutrition, and

4) the Harvard Division of Nutrition Annual Symposium. This day-long symposium focuses on relevant topics in Nutrition research, and this year was entitled "Nutrition in Women's Health" with lectures on Bone, Cancer and Cardiovascular Disease.

For trainees interested in specific research areas, there are a number of research symposia, for example for researchers training in enterocyte function and gut absorption, there is an MGH and Mucosal Immunology Seminar Series Fridays at 9:30 am at MGH-East. In addition to these seminar series, numerous additional longitudinal seminars are sponsored by the various laboratory groups of the MGH, CH and HMS, and more broadly in the Boston biomedical community, for example, the Endocrine and Minieral Metabolism Units at the MGH sponsor a multidiciplianry calcium rounds discussing clinical and research issues related to calcium and bone metabolism. Preceptors are expected to provide guidance in identifying those most worthwhile. Seminars are announced weekly in MGH news, Harvard Focus and Whitehead Institute bulletin (see Appendix D). Special mention should be made of the MGH Research Symposium-Research Tutorial Program sponsored by the MGH Committee on Research. This series has been established by the MGH as a tutorial program aimed primarily for research fellow and trainees. Two lecture series are offered annually (Fall and Spring) dealing with selected basic science topics and laboratories exercises in molecular biology techniques. Hospital support makes it possible to enlist prominent scientists from throughout the country and abroad for this enrichment program. (See Appendix D).