The Multidisciplinary Research Training Program in Lung Diseases: Overview
The University of Michigan Multidisciplinary Research Training Program in Lung Diseases has been in existence since July 1, 1993. The initial program was directed by Galen B. Toews, M.D. and supported research training for four post-graduate trainees. The Training Program has been continuously funded since its inception and has provided research training for over 100 research scientists. While the program has evolved considerably over the past 23 years, the foundations on which the program was build remain intact. Our T32 program is designed to train outstanding M.D. and Ph.D. scientists for investigative careers as full time members of a faculty of a medical school or university, or for careers in full time research. The main focus of this program involves intensive training in a single area of research in the laboratory or Clinic/Hospital under the supervision of a team of faculty trainers combined with broad-based exposure to lung-related research in other disciplines. Molecular, cellular/tissue, animal modeling, genetic, epidemiologic, bioinformatic and patient-oriented approaches are utilized. The strongest asset of this training program is the quality of the faculty trainers and their commitment to a multidisciplinary and translational approach to research questions of common interest. Trainees benefit from an environment in which M.D. and Ph.D. scientists from clinical and pre-clinical departments have teamed effectively to forge productive collaborations in basic and translational research. The educational program provides personal instruction designed specifically for each trainee, as well as a core curriculum, small group workshops, seminars and courses, and opportunities for advanced degree training. The educational program is designed to: 1) provide a broad knowledge of modern biomedical science; 2) provide didactic and experiential training in the intellectual and philosophical approach to modern investigation; 3) develop writing skills; 4) develop teaching skills; and 5) correct any deficiencies in past scientific training. The research program constructed for M.D. trainees is integrated with their previous and concurrent clinical experiences to provide them with investigative tools to address important pulmonary disease-related questions. Programs for Ph.D. trainees provides a clinically relevant, Pulmonary/Critical Care focus for their subsequent research careers. During the past several years, the scope of our Multidisciplinary Training Program in Lung Diseases has been expanded to introduce trainees to new major areas of modern biology, including genetics/genomics, metagenomics, proteomics, metabolomics, stem cell biology, computational biology, and the microbiome. Emerging fields of patient-oriented research have been added or expanded, including health services research and sleep medicine. Our program is truly multidisciplinary, as 56 participating faculty trainers are drawn from 6 different Divisions and 16 different Departments at the University (faculty trainers downloaded below). Funding for program was successfully renewed July 1, 2013, and will continue to support research training for 12 post-doctoral research fellows.
Program Leadership Program Director: Dr. Standiford serves as Program Director for our T32 program.
Theodore J. Standiford, M.D. is a Professor of Medicine and Interim Chief of the Division of Pulmonary and Critical Care Medicine at the University of Michigan. He has had continuous NIH grant funding as Principal Investigator for the past 20 years and served as the Program Director of theUniversity ofMichigan SCOR in Acute Lung Injury (2000-2002) andUniversity ofMichigan SCCOR in Acute Lung Injury (2003-2009). Dr. Standiford has served as a permanent member of the NIH Lung Biology and Pathology (LBPA) and Lung Cell and Molecular Immunology (LCMI) Study Sections. He served as a member of the American Lung Association Research Fellowship and Career Investigator Award Committee from 2000-2004, and Chair of this committee from 2004-2009. He is an elected member of the American Society for Clinical Investigation (ASCI) and the Association of American Physicians (AAP). Dr. Standiford currently serves as an external consultant for two NIH T32 training programs and an NIH K24 patient-oriented research training program. Dr. Standiford has served as a preceptor for 12 post-doctoral research fellows since 2003, eight of which were supported by this T32 program. Five of his trainees have obtained K-series awards, four have received R-series awards, and one is a Parker B. Francis Fellow. Dr. Standiford’s bibliography lists over 200 peer-reviewed publications. As Interim Director of the Division of Pulmonary and Critical Care Medicine at the University of Michigan, Dr. Standiford is responsible for the distribution and utilization of divisional resources at both the University of Michigan Health Care System and the Ann Arbor VA Medical Center.
Associate Program Directors. Drs. Huffnagle and Flaherty serve as Associate Program Directors for our T32 program.
Gary B. Huffnagle, Ph.D. is a Professor of Internal Medicine, Division of Pulmonary & Critical Care Medicine, and Professor of Microbiology & Immunology, University of Michigan. Dr. Huffnagle has been actively involved in education, training and research for over 20 years. He is a nationally and internationally recognized researcher, with over 100 peer-reviewed publications, whose expertise is in host-microbe interactions and mucosal immunology, including microbiome-immune system interactions. He has led the efforts to establish a University-wide microbiome research program (Universityof Michigan Microbiome Research Initiative, UMMRI) to study microbial ecology and host-microbe symbiosis in health and disease, using animal models and clinical samples. Dr. Huffnagle is the Co-director of the newly developing Microbial Systems Science Center at the University of Michigan. Dr. Huffnagle is actively involved in various aspects of the NIH Human Microbiome Project (HMP), including participation in a number of workshops. He has served on many standing and ad hoc NIH study sections as a reviewer and will be appointed as a standing member of the Immunology & Host Defense (IHD) study section in July 2013. He has trained 27 undergraduates, 12 graduate students and 12 post-doctoral fellows (Ph.D., M.D. and D.V.M.). His former trainees hold positions in medical schools, colleges and industry, including a number that have successfully competed for NIH funding. He is actively involved in the pulmonary fellowship program at UM, as well as the graduate program in Microbiology & Immunology. Dr. Huffnagle is also a co-founder and currently steering committee chair for the Interdepartmental undergraduate microbiology major at the Universityof Michigan. For his educational and training efforts in graduate and undergraduate education, the President and Provost of the Universityof Michiganrecognized Dr. Huffnagle in 2010 with a Faculty Recognition Award. Dr. Huffnagle provides leadership in curriculum development and administration to lead the Mechanisms of Disease curriculum of the Core Curriculum (Tier 1) of this Training Program and work with Drs. Standiford and Flaherty in the bi-monthly T32 trainee conferences.
Kevin R. Flaherty M.D., M.S. serves as an Associate Director of the T32 Program. Dr. Flaherty is an Associate Professor of Medicine in the Division of Pulmonary and Critical Care Medicine. He completed a fellowship in Pulmonary and Critical Care Medicine at the University of Michigan and completed a Masters in Biostatistics and Clinical Study Design from the University of Michigan School of Public Health, training that was supported by this T32 program. Dr. Flaherty has an established scholarly niche in the study and treatment of patients with interstitial lung disease. His research involves retrospective database analyses, translational collaborations, and participation in industry and NIH-sponsored clinical trials. Dr. Flaherty served leadership roles in the NIH sponsored Idiopathic Pulmonary Fibrosis Network as Co-Chair of the Measurements and Endpoint Committee and was asked to be on the writing committee for two of the three studies performed by the Network. Dr. Flaherty has over 80 peer-reviewed publications and has maintained NIH R01, K24, and contract funding since his initial K23 award. In addition to research, Dr. Flaherty served as mentor or co-mentor for several T32 trainees. He is an active member and immediate past-president of the Michigan Thoracic Society. He served on nominating and program committees, was Chair-elect (2009) and Chair (2010) of the American Thoracic Society Clinical Problems Program Committee as well as chaired the American Thoracic Society Clinical Year in Review Program from 2009-2011. He has also been a member of the University of Michigan’s Institutional Review Board since 2003. Dr. Flaherty bring his expertise and training in clinical medicine and patient-oriented research to lead the Clinical Coresection of the Core Curriculum (Tier 1) of this Training Program and work with Drs. Standiford and Huffnagle in the bi-monthly T32 trainee conferences.
Administrative Support Tameka Lewis, BBA serves as the Administrative lead for the T32 program and is the Division Grant Specialist who facilitates trainee appointments and terminations. The financial aspects of the program are managed by Susan Vandersluis. Mary Freer, BBA is the Division Administrator who oversees administrative support for the program.
Research Opportunities Available to Trainees.
We have developed a well-established environment of collaborative research that provides a wide variety of opportunities for multidisciplinary research training. The overarching theme of our Training Program is based on research initiatives that integrate basic biologic processes and modern scientific approaches into multidisciplinary disease-oriented translational research. Basic and clinical research programs continue to be organized around an interactive, multidisciplinary approach to research and research training. This includes basic research in the fields of cellular immunology, mediator biology, pulmonary epithelial cell biology, mechanisms of pulmonary inflammation, fibroblast biology, stem cell biology, regulation of gene expression, functional genomics, metagenomics, metabolomics and host defense. Opportunities in patient-based research are diverse and expanded since the last funding cycle. Interactive groups of investigators with interests in fibrotic lung diseases, acute lung injury, and chronic obstructive pulmonary diseases have active, productive clinical investigative programs. Investigators with interests in biostatistics, epidemiology, economics, health care organization and financing, medical education, clinical study design, clinical outcomes, and health care education are available. Fifteen faculty are available in the Patient-based Studies Program.Moreover, it remains an important objective for our program that we offer training options in both laboratory and patient-oriented research.
Processes: Our training grant offers research opportunities in many areas of basic biology. Particular areas of emphasis include: i) Host-pathogen Interactions; ii) Lung Injury and Repair; iii) Airways Disease; and iv) Transplantation Biology.
- Host-pathogen Interactions: Investigators in pulmonary host defense have a long track record of highly interactive, productive interactions via R01 and VA Merit Review funded grants at theUniversity ofMichigan. Specific areas of expertise include fungal host defense, viral host defense, innate immunity, adaptive immunity, toll like receptor and NOD-like receptor biology Faculty trainers are involved in studies to define the microbiome in the mammalian host and its interaction with pulmonary host defenses utilizing functional metagenomic and immunologic approaches.
- Lung Injury and Repair: TheUniversity ofMichigan has a longstanding history of a productive multidisciplinary approach to understanding basic mechanisms of lung injury and repair. Specific areas of expertise include chemokine biology, sepsis-induced lung injury, toll receptor signaling in non-infectious lung injury, mesenchymal stem cell biology, epithelial cell biology, cell death and autophagy, and influence of environment factors (e.g. mechanical stretch, hyperoxia) on lung injury responses. Both acute lung injury and diffuse parenchymal lung diseases result in fibroproliferative lung diseases, which is an active area of research. Specific areas of expertise include fibroblast biology, epithelial-mesenchymal cell transition, protease biology and viral infection/repair interactions.
- Airway Biology: Faculty trainers have built a comprehensive bench-to-bedside program for identifying basic mechanisms of airway inflammation and disease. Trainers are studying allergic models of airway inflammation, including cockroach and ova-induced asthma. The synergistic effects of tobacco smoke exposure and viral infection is being studied in animal models and patient populations. Cutting edge translational studies using lung tissues collected from patients with COPD as a component of SPIROMICS and the LTRC have employed immunohistochemistry, laser-capture microdissection, PCR and multi-color flow cytometry.
- Transplant Biology: An expanding arena of research has been created within theUniversity ofMichigan's Program in Lung Transplantation and its longstanding programs in bone marrow transplantation. This program has generated opportunities for trainees interested in acute allograft rejection and chronic bronchiolitis obliterans, both of which are major obstacles to long term allograft function and survival. Areas of active investigation include the prognostic and biologic significance of mesenchymal stem cells in the pathogenesis of BOS, re-implantation lung injury, epithelial/mesenchymal interactions, and mesenchymal cell/T cell interactions.
The University of Michigan has been at the forefront of innovative technology that allows for novel hypotheses to be tested in proof-of-concept experimental model systems and diseased humans. While these modern technologies have been integrated into our investigative programs, they have also offered unique training opportunities that have been captured since the last competitve renewal of this program. Specific programs include: i) proteomics; ii) genomics, iii) epigenetics iv) metabolomics; v) bioinformatics/computational biology; and vi) metagenomics & the microbiome.
One of the strengths of our training program is the scope of its disease-oriented translational research, which is supported by large multidisciplinary research projects and by longstanding, well-established, productive collaborative groups of investigators. We have expanded our participation in NIH-sponsored clinical research programs over the past 10 years; these large patient populations, databases, and biological samples provide rich opportunities for our basic scientist trainees to perform innovative basic translational research and for our clinical scientist trainees to work with senior faculty in the development, performance and analysis of national multi-center clinical trials. These rich databases and biobanks form the platform for analytical projects which have led to important publications. Many large disease-oriented research programs exist within the Training Program, focused primarily in three areas of investigation: i) Interstitial Lung Disease (ILD); ii) COPD; and iii) Critical Care. A new area of patient-oriented translational research is in iv) Sleep-related Disorders.
Clinical Research Training.
Patient based research trainees have benefitted from the clinical databases and the ongoing or recently completed clinical investigation supported by the NIH within the Division. These large patient populations and databases provide rich opportunities for our clinical scientist trainees to work with senior faculty in the development, performance and analysis of national multi-center clinical trials. The level of expertise and the number of mentors in patient-based research has increased substantially in our training program. A number of current trainers have all been awarded an M.S. in Clinical Research Design and Statistical Analysis, Dr. Martinez’s and Flaherty are recipients of K24 Awards, and K23 grants have been awarded to several former trainees and now trainers. Two programs that have greatly enhanced clinical training within our program are the On Job/On Campus (OJ/OC) Master’s Program in Clinical Research Design and Statistical Analysis and Robert Wood Johnson Foundation (RWJF) Clinical Scholars Program.
3c.4 Formalized Curriculum.
One of the areas of emphasis for NHLBI T32 programs is to develop new investigators with the necessary competencies and breadth of expertise needed for the future of biomedical research. A universal experience which is central to the research training experience of all trainees is the mentored research project itself, and this certainly provides hands-on exposure to all aspects of conceptualizing and doing research and opportunities for individualized, incremental, and organic development of the trainee’s investigative skills. However, it is important that the mentored research project experience is supplemented and complemented by other in-depth learning opportunities occurring in parallel. However, our trainees come from different backgrounds, research experience and investigative interests, as well as having differences in educational paths (both M.D.'s and Ph.D.'s). Thus, to provide the most effective training experience and achieve the goals outlined by the NHLBI, we have developed and implemented a multi-tiered curriculum. Tier 1 consists of core curriculum lectures, meetings and activities intended to provide all trainees with basic concepts, clinical contexts, questions, approaches and issues in modern biomedical research over a typical three-year training period. Tier 2 training is intended to provide the more in-depth and specific information that trainees working in a given field will require as background preparation for pursuit of their individual research projects. Tier 3 includes degree programs that represent an additional option for accomplishing advanced training. As their research projects demand it, individual trainees can elect additional training in key scientific domains from Tiers 2 & 3 that are more specific to the trainee’s research interest and direction. Finally, each trainee will participate in the Responsible Conduct of Research curriculum. The curriculum and its training tiers are presented below.
- Tier 1: Core Curriculum (required). The Core Curriculum is divided into (1) Mechanisms of disease, (2) Clinical science, and (3) Career Development. The didactic lectures are integrated into the three regular weekly conferences in the Division of Pulmonary and Critical Care Medicine.
- Tier 2: Advanced Training Modules (electives). Tier 2 training is intended to provide the more in-depth and specific information that trainees working in a given field will require as background preparation for pursuit of their individual research projects. Tier 2 training will include modules focused on both basic and patient-oriented research training. Specific training modules include but are not limited to the following: 1) The Postdoctoral Research Training Program; 2) Bioinformatics Training through CCMB; 3) Microbiome Training Workshops; 4) the MICHR Core Educational Series supported by the University of Michigan Clinical & Translational Science Award (CTSA); and 5) formal coursework in Microbiology, Immunology, Biochemistry, and Human Genetics.
- Tier 3: Advanced Degree Programs (electives). Degree programs represent an additional option for accomplishing advanced training. Trainees who are pursuing patient-oriented research require comprehensive and formal training in relevant fields such as clinical research design, epidemiology, health economics, and advanced biostatistical methods. For all such trainees, this will be accomplished by formal matriculation in either of two unique programs: The On Job/On Campus (OJ/OC) Master’s Program in Clinical Research Design and Statistical Analysis and the Robert Wood Johnson Foundation (RWJF) Clinical Scholars Program.
- The On Job/On Campus (OJ/OC) Master’s Program in Clinical Research Design and Statistical Analysis offers a rich opportunity for trainees to acquire the necessary skills and methods to perform clinical research, including expertise in epidemiology, biostatistics, clinical trials program evaluation and technology assessment. The OJ/OC program allows trainees to obtain their M.S. degree following an 18-month period in which one 4-day weekend per month of intensive instruction and in-class workshops are supplemented by reading and on-line homework assignments in the intervening interval. This program can be completed simultaneous with the trainee pursuing his/her own research project, and the data from the trainee’s own project can be utilized for in-class assignments. The Master's Degree program includes concepts of validity, reliability, causal relationships, role of randomization, and standards for comparison and sampling. Methods for designing studies related to research outcomes, decision analysis and cost utility analysis are included. Instruction is provided in data collection methods, including questionnaire construction, survey techniques, measurement and standardization problems, concepts and criteria of normalcy and disease and diagnostic criteria. Statistical techniques address and include hypothesis testing, as well as mathematical modeling and demographic techniques.
- Robert Wood Johnson Foundation (RWJF) Clinical Scholars Program. Driven by our expanding opportunities in health services research, we have incorporated the Robert Wood Johnson Fellows (RWJF) Clinical Scholars Program into our advanced degree T32 offerings. The RWJF Clinical Scholars Program is a 2-3 year training program that provides skills and perspectives vital to excelling in health services research. The program consists of a core series of courses during year 1, and a Research Practicum during year 2. Year 3 is optional and tailored to the specific needs of the trainee. A particular emphasis is training in quantitative and qualitative research methods underlying health services research. The University of Michigan Program is one of four RWJF sites nationally and is under the Directorship of Rodney Hayward, M.D., M.S., one of our trainers). Two members of the Pulmonary Division (Drs. Iwashyna and Colin Cooke) are faculty within the RWJF program, with Dr. Iwashyna serving as Associate Director.
Mentorship. One of the fundamental objectives of this training program is to ensure that trainees receive adequate mentorship, and that mentorship is taught and evaluated.
Selection of Mentor: All trainees have free access to Program Faculty. A formal orientation process exists to introduce trainees coming from within the Pulmonary/Critical Care fellowship program to available research opportunities and interests of Program Faculty. Ph.D. Trainees from outside the Pulmonary/Critical Care fellowship program will likely have been attracted to the Training Program by the prospect of working in a particular laboratory environment. Although their choice of a mentor is likely to be somewhat predetermined, assurances will be made that prospective trainees are aware of the scope of available opportunities.
Once a prospective mentor is identified by the trainee, the Program Director presents the trainee's choice to the Steering Committee. The Committee will evaluate the trainee's selection, based on: i) evaluation of the mentor's expertise related to the specific research question proposed by the trainee, ii) availability of adequate space, equipment, and financial resources for the trainee to successfully execute their research plan, and iii) willingness and ability of the mentor to commit adequate time to supervising the trainee. If the Steering Committee approves of the trainee's choice, they will also make recommendations as to the composition of the trainee's Advisory Committee
- Group Mentorship: A primary mentor is defined for each trainee who is responsible for the fellow's training and career development. In many instances, a co-mentor will be involved in a team-based research project. A team mentoring approach provides several advantages. First, it encourages fellows to work at the interface between disciplines. Second, it develops the necessary attitudes and skills needed for team research. Third, it provides the trainee with complementary perspectives on the conceptualization and execution of a research project as well as on career development. In some instances, co-mentoring by a senior and a junior faculty member allows the trainee to benefit from the experiences of the former in project definition, hypothesis development, career advice, networking, and grant preparation, and from the latter in day to day supervision and technical troubleshooting. Fourth, a team mentoring approach allows less experienced trainers to learn from more experienced partners.
- Individual Trainee Advisory Committees: At the end of the first year of Pulmonary and Critical Care fellowship training, or at the time of entry for trainees coming from outside the program, the Program Director will assign a Research Advisory Committee. It will be composed of 2-3 faculty (in addition to the mentor and, if one exists, co-mentor) who are not involved in the day to day aspects of the trainee’s project. At least one member of the committee will come from outside the Division of Pulmonary & Critical Care Medicine. The specific functions of the Advisory Committee will include: i) identifying other potential faculty who may profitably advise/collaborate on the trainee's project, ii) selection of appropriate course work or additional training, based on the trainee’s educational background and the needs of the project, iii) assistance in selecting topics and preparing research seminars and oral presentations at national meetings , and iv) joining with the mentor in reviewing drafts of manuscripts and grant applications. The Advisory Committee will also provide continuity to the trainee's education by performing the semi-annual reviews of the trainee's progress and transmitting these evaluations to the T32 Steering Committee.
Program Success The combination of the formal training program put in place, effective mentorship at all levels, and vigilance in the evaluation process have been instrumental in our success as a post-graduate training program. Of the Ph.D. trainees that have completed the program in the past 10 years, 87% have appointments at academic institutions or the equivalent or biomedical industry. Seven of these trainees have won national research grant awards (one R15, two R01s, one R56, one K22, four Parker B. Francis Awards, two VA Career Development Award, one VA Merit Award, and one Presidential Early Career Award for Scientists and Engineers). Of the M.D. trainees who have completed the Program in the past 10 years, 89% have faculty appointments at academic institutions, and over 50% have been awarded K series, R series, VA Merit, VA Career Development or major independent foundation Awards. Six of these trainees are the Principal Investigator of at least one R01 or Merit. Thus, the Multidisciplinary Research Training Program in Lung Diseases has been very successful in this NHLBI area of emphasis.