The course provides an overview of the process of carcinogenesis and tumor development, risk factors and prevalence of site specific cancers and the methods for identifying risk factors and familial resemblance of cancer risks. (Redesigned Winter 2004)

This course was first offered in winter 2005 and introduces students to mathematical and statistical models and concepts underlying current approaches to computational analysis of functional genomics and proteomics data.

Students are taught the knowledge and skills in selecting optimal study designs and applying the appropriate statistical methods for each design.

This is the capstone course for the MECEH and provides a broad overview of genetics of complex diseases including epidemiology principles, population and family-based genetic studies for finding diseased susceptibility with loci, choice of populations, and analytical approaches. The course have lecturers from the tree primary participating departments.

This may be 1 of the 3 molecular genetics courses that the student may opt to take. The objective of the course is to teach Mendelian principles Bayesian approaches, the genome structure and resources available on the internet, chromosome structure, meiosis and structural variation. It is now offered yearly and became an option for the our MECEH students spring 2005.

This one quarter course covers a broad spectrum of issues relating to the genesis and progression of cancer. Some topics that are covered include cell kinetics and cell cycle regulation in normal and cancerous cells, onco-genes and growth factors, tumor suppressors, the genetics of cancer, mutation and environmental exposure, signal transduction and the role of the immune system in cancer.

(Required course for PhD students): This course will be required for PhD students entering the program in 2006, the first year of the renewal. It will be taught for the first time in 2005/2006 academic year. The objective is to expose students to the structure, content and evolution of genomes. Examples will include the scope and goals of genomics and bioinformatics as dictated by the results of the Human Genome Project, Mapping and Sequencing of the genomes; genetic variation of populations, gene expression profiling and integrating genomics and systems biology.

A new course to be offered in 2005 to cover the role of medical informatics and its relation to patient care, data extraction, databases and clinical research. Evidenced-based medicine and clinical effectiveness research will be highlighted.

The course objective is to show the scientific, technical and ethical issues in the use of biomarkers in epidemiology studies.

Students will learn about molecular techniques used to assess DNA, RNA, and protein for markers of exposure and markers of disease state and susceptibility. Students rotate through a minimum of 4 laboratories (wet and dry (computational/bioinformatics) in 2-week blocks. They will learn about the basic research projects in each of the host laboratories and will learn basic techniques critical to the evaluations ongoing in the laboratory. The technologies addressed will include but are not limited to DNA and RNA isolation; DNA sequencing and mutational analysis; genotyping; biomarkers of exposure such as DNA adducts; protein and nucleic gel techniques; tissue culture; and reporter construct techniques and applications. Interpretation of data and discussion of limitations of techniques will be stressed.

The course covers epidemiological and molecular methods for assessment of the impact of environmental chemical exposures on child health and development. Methods for evaluating primary and secondary prevention strategies are presented.

The course focuses on 1) known genetic factors underlying the inter-individual variation in response to medications and 2) approaches for detecting unrecognized genetic factors that impact response to therapy. This course is taught by a physician and example from clinical practice are used to illustrate.

(Fulfills the biostatistics core curriculum requirement) This course covers the following topics: linear regression, least squares, multiple regression models, model diagnostics & building, correlation analysis, introductory analysis of variance and introductory logistic & Poisson regression models.

The Departmental requirements for the MS and PhD in Epidemiology are described in the DEH handbook as well as below. The additional courses and experiences specific to predoctoral trainees in the program are well described in the handbooks. The PhD postdoctoral trainees are also encouraged to take courses (for audit or credit) to balance out their inter-disciplinary program. A previous PhD post doctoral trainee (Dr. Haynes) took additional courses in Molecular Genetics as well as Pediatric Environmental health, Genetics of Complex diseases and had 2 laboratory experiences.

The PhD post doctoral trainees in molecular biology will be encouraged to take basic epidemiology courses as well as courses in statistical genetics. With the PhD post doctoral training, their needs will be reviewed by the Director (LeMasters) in concert with their primary advisor(s) and members of the Internal Advisory Committee as needed.

UC is on the quarter system with most courses offered Fall, Winter and Spring. In order to obtain a degree in the DEH, a student must maintain a B average or better in all course work. In addition to the successful completion of course work, a Masters or doctoral thesis based upon original and scholarly laboratory, field, or clinical research is required for the degree. Each student must submit “A Statement of Intent” to the Degrees Committee through his/her advisor. This statement is a brief (3 single-spaced pages excluding references) description of the proposed thesis outlining its background, objectives, hypothesis, specific aims, methods, significance/relevance to environmental health, and time table for completion. The student or his/her advisor must have obtained Institutional Review Board Approval (IRB) from either UC College of Medicine or the Cincinnati Children’s Hospital Medical Center, and document this approval in their Statement of Intent for their research proposal. Approval from the Degrees Committee indicates that the work will demonstrate the student’s powers of critical evaluation. The student and primary advisor suggest names of those willing to serve as members of the Thesis Advisory Committee to the Degrees Committee which also reviews the proposal for adequacy in terms of expertise for all areas of the student’s research. The student’s Thesis Advisory Committee must meet at least twice a year and submit a yearly report which is reviewed and signed by the advisor and student; a copy becomes part of their permit record. A major strength of the program is the depth and breadth of expertise available allowing for broad research opportunities. All trainees are given considerable support in preparing abstracts, presenting at meetings publishing their research and writing grant proposals. Below is a description of the three programs for predoctoral and postdoctoral training.

Predoctoral students are accepted based on their GRE scores, generally above 700/area, GPA usually above 3.5, undergraduate degree in areas of molecular biology, math or related areas, and strong recommendations. Further, their personal statements must show a strong interest in molecular epidemiology and/or pediatric health and excellent writing skills. Both Department of Environmental and Public Health Sciences (DEPHS) and Department of Molecular Genetics have around 100 applicants. Prospective applicants for the MECEH program always are pre-screened by 2-3 members of the MECEH admissions committee.

All degrees are awarded by the DEH, UC-COM. For the PhD degree, the DEH requires that each student spend at least 3 years of full-time graduate study, or its equivalent, of which 1 year must be at the UC campus. Full-time Ph.D. students registered for 12-15 graduate credits per quarter. All students are required to maintain an overall B average and to obtain grades of A or B in all core courses. The MECEH trainees are required to take 3 courses in molecular genetics including a capstone course in the Genetics of Complex Diseases organized by Dr. Deka and taught by faculty from all 3 participating programs. They are also required to take 2 courses in statistical genetics (Chakaborty), a course in: Molecular Epidemiology and Pediatric Environmental Health (Lanphear and Dietrich).

The doctoral student must complete 135 graduate credits. Students may be accepted into the predoctoral program directly after completing their undergraduate degree. If the student does not have a Masters degree he/she is strongly encouraged to obtain it in the course of their study which usually represents their first publication as lead author. The course of study for those without a Masters degree is generally 4-5 years while those entering with a Masters may complete within 3-4 years. After the first 2 years, core and required courses and lab rotations are completed. Typically, completion of the qualifying exams and doctoral dissertation requires an additional 2-3 years. The student is expected to have at least 3 publications by graduation. The Qualifying Doctoral Examination consists of 2 written and 1 oral exam. The Degrees Committee appoints the Qualifying Examination Committee and the student’s primary advisor is ineligible to be a committee member. The committee consists of no less than 3 voting members of University Faculty, 1 of whom must be from outside the DEH. The candidate must prepare and submit 3 short, unique mini-research proposals. Each of these 3 proposals must focus on different outcomes and study design areas. Each mini-proposal, not exceeding 3 single-spaced typewritten pages in length, should explore a topic in sufficient depth to show that the critical questions raised are not trivial and worthy of detailed investigation. The proposals should present at least 1 clearly stated hypothesis, logically developed aims and methods and show evidence of creative thinking. If the 3 mini-proposals are of sufficient quality, the exam continues to the next stage. The committee will then select 1 of the 3 mini-proposals for expansion into an NIH type RO1 full grant proposal. The expanded proposal must include a detailed literature review and study plan and is presented to the committee for evaluation. The final step is the oral examination. The student is examined over all aspects of epidemiology and biostatistics in the context of the proposal selected by the Committee.

Following successful completion of the exams, all students must do an original doctoral dissertation. The dissertation committee is comprised of at least 3 members with 1 outside the DEH. The Degrees Committee first reviews the dissertation thesis proposal and committee. The Degrees Committee determines approval of the topic, design and the selected dissertation committee members. The dissertation research takes from 1-2 years, depending on the need to obtain data and the student’s ability to make rapid progress. Students take dissertation credits during this period. Generally, no later than the end of the fifth year of training, students are expected to complete and orally defend their dissertation research. The role of the Program Director (Dr. LeMasters) is to follow the progress of the trainee, ensure that the process goes as smoothly as possible, and resolve any major problems that arise. The trainees and their advisory committee work collaboratively to describe the progress thus far and plans for the coming year. Primary decisions regarding curriculum, dissertation research, and related issues are made principally by the trainee and his or her primary advisor/advisory committee. The primary advisor and committee is the principal source of guidance, helping to provide professional opportunities for the trainee to review grants or manuscripts and find other career development activities.

The postdoctoral clinician program is more flexible in keeping with the specific needs of the clinicians to balance clinical experience, didactic course work, and research and laboratory rotations. The Primary Advisor(s) along with the trainee create a course schedule based on their previous training. Thus, their post doctoral training is 2-3 years allowing time for completing requirements. The typical trainee has finished their residence and has been accepted for a sub-specialty fellowship. The trainee must first be accepted in the DEB before consideration for the MECEH training including providing a personal statement. Typically, the MD applicant has simultaneously discussed possible admission into the MECEH program with the Director (LeMasters). Prospective applicants are interviewed by 2-3 members of the admissions committee and acceptance decisions are similar to the PhD program and based on their research interests and likelihood of pursuing a career in academic medicine. They follow a similar course load as the non-MD students in the Masters program. Courses may be waived if the advisor deems this to be appropriate with regard to their previous clinical training. They also have 3 quarters of lab rotations. Courses in Introduction to Clinical Epidemiology, Introduction to Biostatistics and Molecular Epidemiology are now being offered in the summer in a compressed time frame (as well as again during the regular academic year fall through spring) to specifically accommodate the clinicians who begin their clinical fellowships July 1st. A Master’s student must complete 45 graduate credits excluding thesis research. Postdoctoral trainees in the MECEH must take 2 rather than 3 courses in molecular genetics, and 1 not 2 courses in statistical genetics as well as molecular epidemiology, genetics of complex diseases and pediatric environmental health.

The traditional postdoctoral training may be 2-3 years depending on previous experience. It is less structured as these trainees do not generally work for a degree. They nonetheless take full advantage of the coursework, consulting, seminars, and research opportunities available to predoctoral students. The goal of our post doctoral training is to take qualified PhD-level scientists and balance and augment their previous background toward research in molecular methods in issues related to children’s environmental health. Hence, epidemiologists will do research with a molecular focus and molecular biologists will understand and augment their molecular biology expertise with incorporating epidemiology and biostatistical/bioinformatics techniques and principles in their research. All are expected to gain experience on interdisciplinary teams. In general this program works as follows. After screening interviews and discussions with the Program Director (Dr. LeMasters) and appropriate faculty/preceptor, the postdoctoral trainee has course work, attends seminars and quarterly meetings with all the MECEH trainees. At the quarterly meetings, the students rotate presenting their research and discussing their progress. The vast majority of their time is spent on research and each are expected to publish 3 papers, present their findings at National conferences and submit a grant before leaving the program.

The MECEH trainee is required to have 3-quarters of laboratory rotations of which 2 must be in wet laboratories emphasizing genetic technologies and 1 may be in a dry lab related to statistical genetics/computational medicine or epidemiology studies using genomics methods. A trainee whose research is laboratory based will spend considerable more time in the laboratory, as much as is deemed necessary. Trainees rotate through state-of-the-art laboratories acquiring the ability to conduct cutting-edge research methods. Prior to the lab rotation, students are given a written overview of the potential laboratory opportunities available to them and these are discussed with the Program Director (Dr. LeMasters) and their Initial Advisory Committee. The student then meets with the faculty preceptor of the laboratories and has interviews discussing the potential experience. Next, in conference with the student and the proposed laboratory and preceptor, the laboratory experiences are selected. Though this system has worked well, beginning in 2006 each trainee will have an overview in the fall where they can actually have a 2 week rotation in 4 labs to gain a better understanding of the experience before actually beginning. As outlined above under Faculty Research, the expertise of the faculty and their research interests are within the broad areas of common and complex pediatric diseases, molecular toxicology, pharmacogenetics and genomics, which form the basis of molecular epidemiology. All laboratories are equipped with the most updated and modern equipment (such as automated DNA sequencers) for performing these studies and are manned by highly experienced research associates, technicians and graduate students. More recently, a new Genomics and Microarray laboratory was established and housed in the DEH as a part of commitment of the University of Cincinnati to augment and advance research in genomics, proteomics and bioinformatics (see Resources for additional details). These resources will provide exposure ranging from identification of disease genes and using population based epidemiological approaches combined with molecular techniques to elucidate association and progression of diseases due to environmental insults. Prior to the laboratory experience, the trainee and faculty decide on what the experience will entail and write a brief proposed course of study and the joint expectations. A copy is given to the program director. Trainees do a written evaluation on the quality of the experience after each laboratory rotation. This written evaluation is kept in the trainee’s file. It is the responsibility of each faculty member to provide an oral evaluation of the laboratory rotation to the trainee at the end of his or her rotation.

University seminars for professional development are strongly encouraged for the MECEH trainees. All MECEH trainees and all students from all divisions of the DEH attend seminars hosted by the DEH every Wednesday morning with national and international experts in environmental health science. These Wednesday seminars are held Fall, Winter and Spring quarters and provide 1-1 time during a pizza lunch for the trainees to interact with these national experts. During the last three years Drs. LeMasters, Lanphear and Deka co-organized 2 seminar series devoted to issues in children’s environmental health. Trainees also attend a Thursday brown bag lunch epidemiology seminar. All trainees have the opportunity and are strongly encouraged to present at these seminars. These seminars are well attended by trainees. The MECEH program alerts trainees to all UC-COM and CCHMC workshops, and pays the registration fee, if needed.

Each of the trainees is mentored in grant writing and oral presentation through their seminar presentations, the course “Design and Management of Field Studies” which instructs students on grant preparation and their individual work with mentors. The MECEH program encourages attendance and presentation at national meetings, and a full list of the over 30 national meetings attended is provided. Each year, all trainees present their research during the External Advisory meeting before almost all of MECEH faculty. The MS and PhD students are required to submit their thesis research for publications. As an additional part of their professional development and transition to independent investigator, all trainees are expected and strongly urged to work on a grant application either as principal or co-investigator.