Training within the Systems Genetics and Genomics Unit of the Channing Division of Network Medicine is focused on two post-doctoral training grants: an institutional T-32 and an institutional K-12 from the Division of Lung Diseases (DLD) of the National Heart, Lung, and Blood Institute (NHLBI). The T-32 has been in continuous operation for the past 37 years. What follows below is a description of the two grants and the training resources and infrastructure of the research group. In general, post-doctoral fellows, either MD or PhD, come to the lab and spend two to three years on the T-32 followed by one to two years on the K-12 as they transition to their own entry level grant. Entry into the K-12 is dependent on having submitted a K series grant to NIH. Most fellows transition rapidly from the K-12 to their own independent funding.
The overall goal of this T-32 program is to train clinical pulmonologists in the research techniques of respiratory epidemiology, genetics, genomics, and network medicine. The primary research focus has been on asthma and chronic obstructive pulmonary disease (COPD), although other major research concerns have been addressed as well (e.g., the health effects of air pollution and the occupational and environmental exposures that are important in relationship to airway diseases).
The T-32 program offered by our Division is the only training program funded by the NHLBI that focuses specifically on genetics and genomics and population-based research in obstructive airway diseases, with a unique combination of research efforts in asthma genetics, asthma pharmacogenetics, asthma genomics, COPD genetics, COPD pharmacogenetics, COPD genomics, epigenetics, rare variant analysis, and lung developmental genomics. Our program has evolved from being primarily one focused on chronic disease epidemiology to one now focused primarily on genetics and genomics with a minor focus on traditional respiratory disease epidemiology.
The T-32 program entitled "Clinical Epidemiology of Lung Diseases” (T32 HL007427) is led by Dr. Scott T. Weiss, Professor of Medicine and Director of the T-32 grant for the last ten years and Dr. Edwin K. Silverman, Chief of the Channing Division of Network Medicine. Our training program has trained more than 100 full-time faculty, including three members of the Institute of Medicine of the National Academy of Sciences, and six individuals who chair departments across the U.S. and Canada over the past 30 years. In the past 15 years:
a total of 29 trainees graduated from the program;
28/29 (98%) are currently in faculty or research positions across the U.S.;
13 trainees have received K series grants and two others have received similar awards (Clinical Associate Physician Award from the GCRC and a VA career development grant); and
Of the 15 former trainees that received K (or similar) grants, nine have already received R01 grant awards.
As the current trainees advance in their careers, we anticipate that the number of K and R grant recipients will increase substantially. This track record places us at the very top of all NHLBI funded training grants in terms of training performance.
The program has two types of trainees: post-doctoral and pre-doctoral. Most of the post-doctoral trainees are physicians trained in either adult or pediatric clinical pulmonary disease and interested in gaining research experience in respiratory epidemiology. There have been five of these trainees each year. Pre-doctoral students are interested in environmental epidemiology or statistics (either general or genetic statistics) as it relates to pulmonary disease. There have been two pre-doctoral students each year. Both groups of trainees are fully integrated into all activities of the Systems Genetics and Genomics Unit at the Channing Division of Network Medicine. Since the Harvard School of Public Health is located across the street, it is easy for fellows to attend classes and then return to the laboratory for research meetings and conferences. In addition to weekly grant-related meetings and meetings with mentors (often on a daily basis) to review the specific research projects that they are working on, there are a series of didactic meetings as well including regular weekly seminars on work in progress whose specific purpose is the presentation of “unfinished” (often even “unstarted”) work; study design and analysis, rather than results, dominate the discussion. Approximately every three months, completed work is formally presented to the entire research group. In addition, there is a monthly fellows meeting where either a scientific article is discussed or career development issues are presented by a member of the faculty, such as how to prepare a CV, ways to improve a scientific presentation, etc. Since all post-doctoral trainees are research fellows in the Department of Medicine, a wide variety of clinical and preclinical conferences within the Harvard Medical area are available to them. However, approximately half of the trainees’ time is committed to participation in specific research projects.
Each trainee is also registered as a part-time (post-doctoral) or full-time (pre-doctoral) student at the Harvard School of Public Health. Over a two-year period, sufficient course work can be completed to qualify for a Master of Science degree in epidemiology or a Master in Public Health, with an emphasis in quantitative sciences. Alternatively, trainees can earn a Masters in Medical Science degree in Biomedical Informatics from Harvard Medical School. The pre-doctoral trainees can take courses to complete their qualifying exams for their doctoral degree while working on their doctoral thesis. Classroom activity is generally restricted to less than one-third of each trainee’s time since the major focus of the program is research. If necessary, some research time can be counted toward the unit credits required for a degree.
Our T-32 training grant is the only research program in the U.S. that is funded by the NHLBI to do research in asthma genetics, asthma genomics, asthma pharmacogenetics, COPD genetics, and COPD genomics. Over the past six years, we have:
identified replicated genetic associations for asthma (n=12) and COPD (n=4);
identified two novel genes for steroid treatment response in asthma;
developed a predictive test for asthma in adults that has 90% accuracy; and
developed novel methodology for analyzing genome-wide SNP data and for performing family-based genetic association studies.
We currently manage a total of 100,000 blood samples from 58 separate studies being conducted in 123 locations worldwide. We believe that we are poised to make even greater contributions to airways disease genetics over the next ten years.
This K-12 program is led by Dr. Weiss, Program Director, and supported by Dr. Silverman, Co-Director. There are a total of 21 faculty members who participate in the K-12 training program.
Each trainee has both a senior and a junior mentor for each research project that he/she works on. Trainees start with only one project but by the middle of the second year they may have as many as three active investigations. Although trainees rarely switch areas (e.g., from asthma to COPD genetics), they may have projects in several sub-areas within a general area of investigation (e.g., asthma genetics and asthma functional genomics). Depending on a particular project’s needs and complexity, the project staff will meet weekly, every other week, or monthly. Project meetings are attended by all involved investigators and technical personnel. The Program Directors or another senior staff member is involved in every research project and hence is available to monitor trainee participation. Separate meetings are held weekly for each of the major genetics grant projects: Pharmacogenetics, Dutch Hypothesis PPG, Asthma in CAMP and Costa Rica, COPD Genetics, and Functional Genetics of COPD PPG. One of the co-directors attends each of these meetings to monitor trainee-faculty interactions. After an initial period of observation usually prior to joining the laboratory, the trainee formulates a plan with his or her chosen senior and junior mentor. The plan includes didactic courses, at least one research project, and a plan for an independent R01 or K award application. Once approved, the plans are monitored by the senior mentor, the program directors, and the trainee on a monthly basis to see that milestones are being met and that there is no need to change or modify the plans.
We endeavor to achieve an individualized program of educational instruction, field work (phenotyping of subjects for human genetics), and data analysis for each fellow. Given the complexities of the genetics and genomics of complex diseases and the need to learn some molecular biology, as well as statistical and study design issues, this is a significant educational challenge. An individualized program consists of course work, field work, data analysis, manuscript preparation, and grant writing. Given that it is impossible (because of time constraints) for a trainee to begin with field work and finish with writing a paper on this field work, we often have field work going on one project while data analysis is going on in a separate project to accommodate a timeline of completion of training over two years. Field work experience includes home visits and hospital visits in ongoing research projects. The coursework, while essential, is ideally directed toward accomplishing specific goals primarily with regard to data analysis and computer program manipulation, or specific issues in genetics or genomics. At the end of the first year on the K-12 for a trainee with prior quantitative experience and at the end of the second year for a trainee with no such experience the trainee must write their own K series grant (K-08, K-23, K-01) or an R01. To achieve this goal requires that the mentors have developed a plan with the K-12 trainee at the very start of the experience that will lead to independence. This plan has been vetted with the program directors and been assessed at three levels for its scientific originality, probability for funding and potential to lead to independence.