Investigative Medicine
Department of Medicine
Edward S. Harkness Building (ESH), basement 18–20,
785.6842
Ph.D.
Director of Graduate Studies
Keith Joiner (Internal Medicine) (invmed@info.med.yale.edu)
Deputy Director
Sharon Inouye (Internal Medicine)
Faculty
A broad range of faculty from clinical and basic science
departments participate in this program.
Fields of Study
The purpose of this program is to create a special training
pathway for highly select physicians in clinical departments
who are interested in careers in biomedical research. This
program is designed to develop a broad knowledge base, analytical
skill, creative thinking, and the hands-on experience demanded
of clinical researchers devoted to disease-oriented and patient-oriented
investigation. It will provide the candidate with individualized
experience encompassing formal course work and practical experience,
under the supervision and mentorship of a senior faculty member.
Trainees enter the program with a broad range of experience
and interests. Trainees can undertake thesis work in a variety
of disciplines, including: evaluating risk factor and interventions
for disease using modern concepts in quantitative methods
and clinical study design; investigating the biochemical,
physiologic, and genetic basis for disease in the setting
of a Clinical Research Center; or exploring the molecular
basis for a disease from the laboratory standpoint.
Special Admissions Requirements
The Investigative Medicine program is designed for students
with an M.D. degree who have completed two or more years of
postgraduate clinical training. Application to the program
may be made concurrently with application for subspecialty
training in a clinical department at Yale. To be eligible
for the Investigative Medicine program, the candidate must
first be accepted into a subspecialty program (including General
Medicine), at which point the candidate may apply to the Investigative
Medicine program. Students will typically be involved in clinical
training in their subspecialty for the first twelve to twenty-four
months after arrival, and thus will enter the Investigative
Medicine program after having completed two to five years
of postgraduate clinical training. Prospective students who
are already in a subspecialty clinical program at Yale may
also apply to the Investigative Medicine program anytime during
the first two years of that training (approximate).
The most important criterion for selection into the program
is the commitment of the applicant to rigorous training in
clinical investigation. Successful candidates will also need
evidence of high academic achievement in undergraduate and
medical-school courses and completion of residency training.
Test scores from the USMLE are required, and (if available)
the American Board of Internal Medicine, Pediatrics, Neurology,
or other relevant subspecialty disciplines.
Special Requirements for the Ph.D. Degree
The minimum course requirements for the doctorate program
are nine (9) courses. These consist of three one-term core
courses: Principles of Clinical Research, Translational Research
and Molecular Tools Part I, and Practical and Ethical Issues
in Clinical Investigation; one yearlong seminar course: either
Seminars in Clinical Investigation or Seminars in Molecular
Medicine; one intensive practical course: either Translational
Research and Molecular Tools Part II or Quantitative Clinical
Epidemiology; an introductory biostatistics course; the independent
reading course in Investigative Medicine; and a minimum of
two electives in the specific research area. Full-time course
work will extend over twelve months, usually starting in July.
Students must enroll in a minimum of two courses each term.
The majority of course requirements may be completed in twelve
months, with elective courses often taken in the second year.
To complete course requirements, students must achieve the
grade of Honors in two courses (one course if a full-year
course). When requirements are met (typically at the end of
the first year), students submit their thesis proposal and
undertake a qualifying exam. In order to be admitted to candidacy,
students must pass written and oral examinations and submit
a prospectus which has been approved by their qualifying committee.
The remaining degree requirements include completion of a
dissertation project, the writing of the dissertation, and
its oral defense. It is expected that most trainees will complete
the program in four years.
Courses
IMED 610, Translational Research and Molecular Tools Part
II. Elisabetta Ullu. MTWThF 8.30–6
This is an intensive, full-time two-week lecture and
laboratory course. Currently, the emphasis is on protein and
nucleic acid biochemistry, and on gene expression profiling
through DNA microarray experiments. The lectures complement
and extend the laboratory experience. The laboratory course
requires full-time commitment. Consent of instructor required.
Two weeks, August.
IMED 620, Translational Research and Molecular Tools
Part I. Keith Joiner. MTWThF 2–5
Genomics: In this section, students learn how genomics
is influencing both medical research and health care delivery,
and illuminating the genomic discoveries being translated
into diagnostic and therapeutic medical applications. This
course takes an integrated approach, exploring how genomes
are mapped and sequenced, how various computational methods
convert this raw data into information about biology, and
how new experimental methods can provide comprehensive information
about the behavior and function of genes and their products.
Lectures are supplemented with computer laboratory sessions
to reinforce ideas and to provide practical experience. The
majority of the time is spent using computer applications
of bioinformatics tools. The course is designed to provide
practical training in bioinformatics methods including accessing
the major public sequence databases, use of the BLAST tools
to find sequences, analysis of protein and nucleic acid sequences,
detection of motifs or domains in proteins, assembly of protein
sequences from genomic DNA, detection of exons and finding
intron-exon boundaries, aligning sequences (Clustal W), making
phylogenetic trees, and comparative genomics. Structure-Based
Drug Design: In this section, students learn the underlying
principles in structure-based drug design. Lectures are supplemented
with computer sessions devoted to practical learning of basic
principles in protein structure determination, analysis, and
relationship to molecular design. Clinically relevant examples
of this approach are considered. Consent of instructor required.
Two weeks, July.
IMED 625, Principles of Clinical Research. Sharon
Inouye, David Fiellin. MTWThF 2–4
The purpose of this two-week intensive course is to provide
an overview of the objectives, research strategies, and methods
of patient-oriented research. Topics include: competing objectives
of clinical research; principles of observational studies;
principles of clinical trials; principles of meta-analysis;
interpretation of diagnostic tests; prognostic studies; causal
inference; qualitative research methods; decision analysis.
Sessions include lectures and discussion of readings distributed
in advance. Consent of instructor required. Two weeks, July.
IMED 630a, Practical and Ethical Issues in Clinical
Investigation. Henry Binder. W 3.30–5
This termlong course addresses topics which are central
to the conduct of clinical investigation, including ethics
of clinical investigation, scientific fraud, technology transfer,
and interfacing with the pharmaceutical industry. Practical
sessions include: scientific presentations and teaching, NIH
peer review process, journal peer review process, and career
development: models of academia. This course provides guidelines
and a framework for the clinical investigator to write, obtain
funding for, conduct, and present a clinical study. Consent
of instructor required.
IMED 635a or b, Directed Reading in Investigative Medicine. Keith
Joiner.
An independent study course for first-year students in
the Investigative Medicine program. Topics are chosen by the
student, and reading lists are provided by faculty, for weekly
meetings to discuss articles. Fourteen sessions are required;
dates/times by arrangement. Consent of instructor required.
IMED 640a,b, Seminars in Molecular Medicine. Keith
Joiner. M 3–4.30
This yearlong seminar course focuses on the details of
the basic investigation of the biochemistry, cell biology,
genetics, immunology, and molecular biology of human disease
from a sophisticated perspective. At each session, articles
on the basic laboratory investigation of a disease or disease
process (which is well understood at the molecular level)
are selected by the faculty. Faculty provide an overview of
the specific methodologies used to address the hypothesis,
followed by discussion of the articles in a seminar format.
Consent of instructor required.
IMED 650a,b, Seminars in Clinical Investigation. Sharon
Inouye. F 2–4
This yearlong seminar course explores the interface between
clinical strategies and methodologies used to investigate
these topics. A variety of topics are covered in an interactive
seminar format. Articles are selected by the faculty, and
students review and discuss the articles at each session.
In addition, students gain experience in critical evaluation
of study designs and protocol development (in the fall term),
and grant writing and reviewing (in the spring term). Attendance
and active participation are required. The course gives new
clinical investigators tools to conduct their own research
project. Consent of instructor required. Prerequisite: biostatistics
training.
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