Molecular Pathogenesis and Molecular Medicine Curriculum

University campus

To ease your transition into graduate school, we provide you with information about all phases of the program of graduate studies on which you are embarking.  This is a description of program requirements and course descriptions.  Most importantly, we try to convey the spirit of the program, the expectations that the faculty have for successful students, and the mechanisms that we have to help you along.  Remember - your success is our success.

PhD Program

The Department of Pathology and the Committee on Molecular Medicine offer a program of advanced study and research in experimental pathobiology, and in the molecular and cellular physiology of several organ systems. We call our curriculum Molecular Pathogenesis and Molecular Medicine. Areas of emphasis include immunobiology, molecular oncology, and vascular pathophysiology, and disease of cardiovascular, respiratory, endocrine, gastrointestinal, and neuropsychiatric systems.   This broad participation of scholars from basic science, translational, genetics, and clinical traditions provides for the prompt transfer of fundamental discoveries to practical application in the understanding and treatment of such widespread and important diseases.  The department encourages scholarship and achievement and offers flexibility in its program to permit each student to pursue the most effective course of study and research.

Instruction includes courses in biochemistry, defense reactions, cancer biology, immunology, cellular and molecular pathology, and cell, molecular, and genetic biology that are generally completed within the first two years of study.  Each student must select a faculty sponsor who is willing to supervise his or her thesis research.  Such faculty members can be chosen from multiple departments in the Division of the Biological Sciences if the research program is considered suitable by the graduate student advisory committee.

We have a dual mission, combining clinical faculty with basic science faculty whose common interest is the biological mechanisms underlying diseases.  The diversity of faculty reflects the interdisciplinary nature of modern Pathology & modern Medicine.  We consider our faculty to be among the most distinguished researchers in the field and our training program has been very successful over the past 20 years.

Students are admitted to work towards the PhD degree in Pathology.  Because we expect the students to commit full time to the program, all have financial support towards tuition, fees and stipend.  The sources of support are either University funds, research grants or training grants, but we strive to maintain an equal level of financial support regardless of the source.  The program consists of two phases: formal course work and laboratory rotations, followed by independent research towards a dissertation.  Typically, students begin with 1-2 years of course work, chose a dissertation advisor after the first year and spend 3-5 years in research work.  The graduate studies advisory committee (GSAC), consisting of eight faculty, is charged with guiding the program and its students.

Biomedical Sciences Cluster

All PhD programs in the Division of Biological Sciences have been grouped into four clusters, in order to streamline and unify the practices and expectations for all graduate students and afford them flexibility in their career development.  The Ph. program in Pathology/Molecular Pathogenesis and Molecular Medicine is one of five programs that are now grouped together in the Biomedical Sciences Cluster, together with the programs in Cancer Biology, Immunology, Molecular Metabolilsm and Nutrition and Microbiology.  The five academic units share a joint Admissions Committee, several common courses, a seminar series, and additional common events for students and faculty within the cluster. The goal of the cluster system is to encourage interdisciplinary interactions among both trainees and faculty, and to allow students flexibility in designing their particular course of study. 

Students have extensive opportunities for interaction with the three other clusters within the Biological Sciences Division: the Molecular Biosciences Cluster; the Darwinian Sciences Cluster; and the Neurobiology Cluster.  These clusters offer courses and sponsor seminars and symposia open to Pathology/MPMM students.

 

Graduate Studies Advisory Committee

 

This committee monitors and advises all students in the program.  This committee evaluates all preliminary exams for the students, thus maintaining consistency.  This also provides a means to detect any problems at any early timepoint in training, so that the student can receive advice and get back on track in their training.

First Year Advising:
Recognizing that the transition into graduate school is sometimes a difficult challenge, we do all we can to advise and mentor the students through this transition.  Until the students choose a lab in which to pursue their research project, they are expected to meet with the chair of GSAC at least once a quarter, and they are encouraged to communicate with the Chair as often as needed.  The meeting in the Autumn quarter of the first year will be devoted to developing a formal course program appropriate for each student.  In addition to courses, these meetings are also used to discuss possible lab rotations and any other subjects that the students wish to discuss.  In addition, students should feel free to approach and discuss any issue with any of the GSAC members.

Course Work:
All candidates must complete nine graduate course credits, including the three quarter sequence, Pathology 30600, 30800, and 57500.  A fourth required course is the Major Human Diseases journal club.  Additional courses should include genetics, immunology, molecular biology, and cell biology, selected from a large menu of courses offered.  Candidates must also meet the divisional requirements for two quarters as teaching assistants.  Candidates for the MD degree qualify for course credits provided that they have received letter grades in their medical school courses. The number of medical school courses appropriate for credit towards graduate work will be determined by the Graduate Student Advisory Committee.  

To remain in good standing, students must maintain a B average in all graded, formal courses, and receive a B grade or better in the required Pathology/CMM courses. After the first year, GSAC holds a meeting with each student and reviews her/his progress.

Programmatic Core Courses

These four courses, taken in sequence during years one and two, will comprise 3.5 credits.

 

 

Cell Growth, Injury, Repair, and Death (MPMM 57500).
This course reviews the various modes of cell injury that can occur, the basic molecular healing responses, and pathways of metabolic survival or death. This course may be of interest to those interested in wound healing, biological stress responses, molecular chaperones, radiobiology, biomechanics, biomedical engineering, as well as trauma and critical care medicine.  Hamann, Lee.  Autumn.

Signal Transduction and Disease (MPMM 30600).
Topics include receptor ligands, membrane receptor tyrosine kinases and phosphatases, G proteins, proto-oncogenes, signaling pathways, cytoplasmic protein kinases and phosphatases, transcription factors, receptor-nucleus signaling, development and cancer, genetic dissection of signaling pathways, cell growth and cell proliferation, interplay of cell cycle regulators, cell cycle progression and apoptosis, and sensing of hypoxia and mechanical stimuli.  The role of signaling in disease is a theme throughout the course.  Dulin.  Winter.

Molecular Defense Mechanisms (MPMM 30800).
Defense mechanisms which include the mechanisms of inflammation, coagulation, immunological injury, cytokines, complement induced injury, hypersensitivity, autoimmunity and AIDS.  Emphasis is on mechanisms at the molecular level with an introductory lecture and following with discussions of selected recent journal articles which are read and discussed at class sessions.  Boone. Spring.

Major Human Diseases Journal Club (MPMM 39000).
All Pathology Program graduate students must participate in the Biodisease Journal Club throughout their training.  Credit will be given during the student’s first and second years, however it is expected that students will continue to attend and participate in their later years.  Getz, Meredith.  Autumn, Winter, Spring.

 

 

Programmatic Elective Courses

The Making of a Heart (MPMM 30001).
This course will cover our current understanding of the molecular mechanisms regulating the formation and function of the heart and vascular systems.  We will also explore how these basic mechanisms are altered in cardiovascular disease.  Specific topics will include congenital heart disease, hypertension, artherosclerosis, cardiomyopathies, cardiac arrhythmias, and myocardial infarction.  Svensson. Spring.

Molecular Mechanisms of Cancer Biology (MPMM 30900, CABI 30900).
Examines our current understand¬ing of the processes leading to malignant cell transformation.  Topics include comparative properties of normal cells and cells transformed spontaneously or by chemicals, radiation, and viruses; multistage mechanisms in carcinogenesis; metabolic activation of chemical carcinogens; DNA adduct formation; repair of DNA damage; metastasis/invasion; and mechanisms of cancer therapeutics.  Macleod.  Winter.

Molecular Basis of Metabolic Disease (MPMM 30901, MOMN 30901).
This course selects topics in nutrition in which modern molecular and cell biology provide a greater understanding of the regulation of these metabolic pathways.  Wicksteed.  Autumn.

Molecular Biology of Disease (MPMM 32000).
This course will examine specific diseases for which the molecular etiology and pathogenesis are either known, or currently the topic of intensive study.  Topics are included on a rotating basis.  The most recent list of topics included the following:  Leptins and genetic causes of obesity, α1-Antitrypsin Deficiency and Childhood Cirrhosis, Maturity Onset Diabetes of the Young (MODY), Progeria, Hyperlipidemias, Huntington's Disease, Alzheimer's Disease, Sickle Cell Anemia, Osteogenesis Imperfecta, and Cystic Fibrosis.  Meredith.  Winter.

Molecular Nutrition 2 (MPMM 36600, MOMN 36600).
Consideration will be given to those selected topics in nutrition in which modern molecular and cell biology have provided new explanatory power.  Brady, Reardon. Winter.

Modern System Pathology (MPMM 31201).
This course provides in depth study of the disease processes that affect three major organ systems each year, in a 3-year cycle.  Organ system groupings include:  Cardiovascular/Respiratory/Gastrointestinal (Tubes); Obesity/Reproduction/Endocrinology; and Kidneys/ Neural Degeneration/Liver.  Moskowitz. Spring.

Biochemistry Courses

Proteins 1: Protein Fundamentals (BCMB 30400).  
The course covers the physico chemical phenomena that define protein structure and function.  Topics include:  1) the interactions/forces that define polypeptide conformation; 2) the principles of protein folding, structure and design; and 3) the concepts of molecular motion, molecular recognition, and enzyme catalysis.  Prereq:  BCMB 30100, which may be taken concurrently, or equivalent.  Koide, Keenan.  Autumn.

Fundamentals of Structural Biology (BCMB 30500).  
This course emphasizes the basic principles of protein structure determination by X-ray crystallography and NMR spectroscopy. The underlying physical concepts of these methods will be introduced and the capabilities of each will be discussed and compared in context of their uses in de novo structure determination and protein engineering studies.  Kossiakoff, Koide.  Winter.  (This course will not be offered in 2008.)

Proteins 2: Structure and Function of Membrane Proteins (BCMB 32300).  
This course will be an in depth assessment of the structure and function of biological membranes. In addition to lectures, directed discussions of papers from the literature will be used. The main topics of the courses are: (1) Energetic and thermodynamic principles associated with membrane formation, stability and solute transport (2) membrane protein structure, (3) lipid-protein interactions, (4) bioenergetics and transmembrane transportmechanisms, and (5) specific examples of membrane protein systems and their function (channels, transporters, pumps, receptors). Emphasis will be placed on biophysical approaches in these areas. The primary literature will be the main source of reading.  Perozo, Roux.  Winter.

Cancer Biology Courses

Cancer Biology I: Introduction to Cancer Biology (CABI 30800).
Overview of cancer biology, including epidemiology, pathology, diagnosis and staging, and the basis for various therapeutic strategies. Also covered are experimental models for cancer, including the generation and validation of animal models. The course will emphasize several tumor models, such as breast cancer, hematological malignancies, cervical carcinoma, gastrointestinal carcinoma, and sarcomas.  Conzen.  Autumn.

Cancer Biology III: Signal Transduction and Cell Cycle Regulation (CABI 31200).
Topics include receptor ligands, receptor tyrosine kinases and phosphatases, G protein-coupled receptors, signaling pathways, cytoplasmic protein kinases and phosphatases, receptor-nucleus signaling, nuclear proto-oncogenes, cell growth suppression, tumor suppressors, regulation of cell cycle progression, modulation of cell cycle progression and apoptosis.  Du, Lin.  Spring.

 

Cell Biology Courses

Cell Biology 1 (MGCB 31600).
Eukaryotic protein traffic and related topics, including molecular motors and cytoskeletal dynamics, organelle architecture and biogenesis, protein translocationand sorting, compartmentalization in the secretory pathway, endocytosis and exocytosis,and mechanisms and regulation of membrane fusion.  Glick, Turkewitz.  Autumn.

Cell Biology 2 (MGCB 31700).
This course will cover cell cycle progression, cell growth, cell death, cytoskeletal polymers and motors, cell motility, and cell polarity.  Glotzer, Kovar.  Winter.

Genetics Courses

General Principles of Genetic Analysis (GENE 31400).
Coverage of the fundamental tools of genetic analysis as used to study biological phenomena. Topics include genetic exchange in prokaryotes and eukaryotes, analysis of gene function, and epigenetics.  Bishop and Staff.  Autumn.

Genetic Mechanisms (GENE 31500).
Advanced coverage of genetic mechanisms involved in genome stability and rearrangement in lower and higher organisms.  Topics include the genetics of mutagenesis, DNA repair, homologous and site specific recombination, transposition and chromosome segregation.  Bishop.  Winter.

Human Genetics 1: Human Genetics (HGEN 47000).
This course covers classical and modern approaches to studying cytogenetic, Mendelian, and complex human diseases.  Topics include chromosome biology, human gene discovery for single gene and complex disease, non-Mendelian inheritance, mouse models of human disease, cancer genetics, and human population genetics.  The format includes lectures and student presentations.  Cox, Millen, Ober.  Autumn.

Immunology Courses

Host Pathogen Interactions (IMMU 31200).
This course will explore the basic principals of host defense against pathogens and pathogens’ strategies to overcome host immune mechanisms.  The course will address evolutionary aspects of innate and adaptive immune responses, while also studying specific examples of viral and bacterial interactions with their hosts.  The reviews of relevant immunological mechanisms necessary for appreciation of host/pathogen interactions will be incorporated in the studies of specific cases.  Chervonsky.  Autumn
    
Advanced Immunology 1  (IMMU 31500).
Lecture/discussion course that explores the genetic and molecular basis of immune recognition by B and T lymphocytes.  Specific topics to be discussed include the expression of the antigen specific receptors on B and T lymphocytes, immunogenetics, the differentiation of lymphocyte subsets, MHC restriction, cellular interactions and effector mechanism in immune responses, and the role of accessory molecules in cellular interactions.  Consent of instructor required. Bendelac.  Winter

Advanced Immunology 2  (IMMU 32000).
This class will explore the molecular and biochemical mechanisms by which lymphocytes are activated in response to antigen. This will include an in-depth consideration of the signal transduction pathways utilized by not only the antigen receptors but also by those receptors which provide co-stimulation, those which modulate lymphocyte activation and those which mediate lymphocyte localization. Finally, we will attempt to understand how these complex signal transduction cascades integrate to drive such processes as lymphocyte development, tolerance and the immune response.  Clark and Kee.  Spring.

Selected Topics in Immunology  (IMMU 35500).
This course is an advanced literature analysis/discussion course intended primarily for graduate students in Immunology.  It will involve an in depth analysis of a particular topic in Immunology, which will vary from year to year.  Emphasis will be placed on development of critical thought in evaluation of the scientific literature. Recent courses have included:  (1) Antigen presentation of pathogenic organisms.  (2) Clinical issues in transplantation and autoimmunity.  (3) T cell development and activation.  Guevara.   Spring.

Microbiology Courses

Bacterial Pathogenesis  (MICR 34000).
Bacterial pathogens of human, animal and plant organisms, their infectious strategies and molecular mechanisms of causing disease. Dr. Schneewind. Winter.  

Introduction to Virology  (MICR 34600).
This class on animal viruses considers the major families of the viral kingdom with an emphasis on the molecular aspects of genome expression and virus-host interactions.  Our goal is to provide students with solid appreciation of basic knowledge as well as instruction on the frontiers of virus research.  Dr. Pilipenko. Winter.

Advanced Topics in Virology  (MICR 35000).
The aims of this course are to examine viral host interaction using herpes simplex and retroviruses as models.  The course will focus on the means by which viruses take over the host cells, the mechanisms of host defenses to infection and the viral functions which enable the pathogens to overcome the host.  Drs. Golovkina, Roizman. Spring.

Molecular Genetic Analysis of Bacteriophage (MICR 33000).
Phage are the most abundant and fastest growing biological entities and are involved in many natural microbiological processes. This course will examine a series of bacteriophage that have been instrumental in our understanding of genetics and molecular biology with an emphasis on their properties and the methods for which they are used in current and potential biological studies and in biotechnology.  Casadaban.  Spring.

Molecular Biology Courses

Fundamentals in Molecular Biology (MGCB 31000).  
The course covers nucleic acid structure and DNAtopology, recombinant DNA technology, DNA replication, DNA damage, mutagenesis and repair, Transposons and site-specific recombination, prokaryotic and eukaryotic transcription and its regulation, RNA structure, splicing and catalytic RNAs, protein synthesis, and chromatin.  Staley. Storb  Winter.

Molecular Biology 1 (MGCB 31200).
Nucleic acid structure and DNA topology; methodology; nucleic-acid protein interactions; mechanisms and regulation of transcription in eubacteria, and of replication in eubacteria and eukaryotes; mechanisms of genome and plasmid segregation in eubacteria.  Rothman-Denes.  Winter.

Molecular Biology 2 (MGCB 31300).
The content of this course will cover the mechanisms and regulation of eukaryotic gene expression at the transcriptional and post-transcriptional levels. Our goal is to explore with you research frontiers and evolving methodologies. Rather than focusing on the elemental aspects of a topic, the lectures and discussions will focus on the most significant recent developments, their implications and future directions. Singh, Staley.  Spring.

Pathology Courses

Research in Pathology  (MPMM 40100). 
Open to a limited number of qualified students and graduates in medicine.  Meredith.

Readings in Pathology.  (MPMM 40200).  
Selected readings in pathology/MPMM.  Consent of instructor.  Getz and Staff.

Laboratory Rotations

Graduate students in Molecular Pathogenesis and Molecular Medicine are encouraged to do two rotations.   Lab rotations should be completed by the beginning of the second year so that the student can settle on a thesis advisor.   The research interests of the various faculty are described during the All Stars seminar series, sponsored by the Biomedical Sciences Cluster, during the Autumn and Winter quarters.  This forum provides a convenient venue for the students to choose lab rotations.

Rotations will consist of small research projects in different laboratories.  The expectation is that these projects will provide:
1) An opportunity for each student to become familiar with the conceptual and technical features characteristic of potential thesis projects.
2) An opportunity for faculty members to evaluate the research strengths of graduate students.

As such, students will be expected to spend enough time in the laboratory to accomplish these goals.  Scheduling of the rotations will depend on the student’s background, course work and experience.  For students who have less research experience or more limited background, it might be best to delay a rotation until the Winter Quarter.  Students who enter the program with specific areas of research interest may wish to begin their rotations in the Autumn quarter.  They are advised, however, not to pin their hopes on one lab and to rotate nonetheless.  

When a student settles on a lab for dissertation research, the student needs to notify the Chair of GSAC of her/his choice.

Preliminary Exam

Purpose:  for the student to demonstrate that he/she is qualified to begin independent research by preparing and defending a research proposal.  The student should be able to define a scientific problem of significance, design experiments to address it, anticipate the possible problems and results, and discuss what those results would signify.

1.  Eligibility and Scheduling - Students in good academic standing are eligible to take the preliminary examination after they have completed their required and elective course work (usually nine courses and their research rotations), and have met all other requirements of the department.  For most students, the thesis proposal is scheduled during the Summer quarter corresponding to the fourth quarter of full time residence in our graduate program.  The GSAC and its chairman are responsible for determining eligibility and for scheduling the examination.

2.  Format - The preliminary exam consists of a written research proposal structured in an NIH format, a short oral presentation based on the proposal, and an oral examination. 

3.  Research Subject – Students may choose any area of contemporary pathology that interests them.  However, the specific research topic chosen must not be directly related to a) a student’s projected thesis project, b) a research proposal previously submitted for a course (at Chicago or elsewhere), or c) a previous research experience obtained during a research rotation or during undergraduate years.  Students who are concerned about what is (or is not) new enough or different enough should seek guidance from the chairman of the GSAC.

 

After the student has passed the preliminary examination by successfully defending the research proposal, the student and faculty mentor assemble a doctoral committee (also called a thesis committee) consisting of five members of the Faculty of the Division of the Biological Sciences with expertise in the area of the student's thesis research.  At least two of these should be members of the Department of Pathology or the Committee on Molecular Medicine, and one of these two should be a member of GSAC.  The thesis advisor is a member of the thesis committee, but should not serve as its chair.  The composition of the doctoral committee must meet the approval of GSAC.

 

Doctoral Research, Thesis Proposal and Defense

One of the strengths of the University of Chicago is that we allow and, in fact, encourage, students to perform their thesis work in the laboratory that most precisely fits their interests and strengths, involving laboratories from multiple departments.  We believe that this policy provides optimal exposure of the trainees to the best scientific environment possible while keeping their interests at the forefront.  Although students may be assigned to an ongoing problem in the laboratory, they are typically encouraged to develop an independent problem as quickly as possible.

The thesis proposal is designed to test the student's mastery of knowledge in Pathology and Medicine and related fields, as well as their ability to integrate knowledge.  It consists of an oral defense of the student’s research proposal before the GSAC.

The format of the proposal is based on an NIH postdoctoral fellowship application.  It should be scholarly and reflect your own thoughts and ideas.  The proposal should be hypothesis-driven, should state the general research objectives, and include a description of the background and the rationale for the proposed research.  The specific experimental approaches to be used to achieve the objectives should be presented in sufficient detail to permit evaluation of the experimental design, and you should be prepared to justify why you choose a particular approach.

After successful presentation of the thesis proposal and completion of all course requirements, students may be entered into candidacy for a PhD.

The progress of the research is monitored through annual meetings of the doctoral committee until completion of the dissertation.  The chair of the thesis committee prepares a short written synopsis of each annual meeting.  Students are encouraged to use the expertise of the members of their thesis committee to their advantage and consult with them frequently even outside the annual meetings of the committee.

It is expected that most trainees will begin thesis research at the start of their second year in the Program, and complete their research by the end of their fifth year in the Program.  MD/PhD students usually complete the research portion of the program in 3-4 years.  This amount of time is sufficient when combined with elective time available in the medical curriculum to provide sound theoretical and practical experience.  Students engaged in a straight PhD program generally complete the program of study in 4-5 years.

Upon completion of an original, research-based, PhD dissertation, the student presents the research in a public seminar to the Division of the Biological Sciences, and defends the thesis before the thesis committee.  The scientific results in the dissertation must be of a quality to warrant publication in major journals.

Teaching Assistantships

We view teaching as an indispensable part of the training program, for several reasons: 
1. The best way to learn a subject is to teach it to others. 
2. The ability to teach is a critical part of a career in academic research.
3. It will be an essential tool of trade for those of our graduates who pursue science teaching or science communications careers (e.g. museum or news media work).

All graduate students in the Biological Sciences Division are required to complete two teaching assistantships in two different quarterly courses.  Students may TA an undergraduate course, graduate level course or a medical school course.  The Division also sponsors a TA Training Course that may satisfy one of the TA course requirements.  TA opportunities and details can be found on the BSD's Office of Graduate and Postdoctoral Affairs Teaching Opportunities website.  Students must contact the course directors to make arrangements for each TAship.