I. INTRODUCTION

Aims and Objectives of the Program:

A graduate program in Experimental Pathology leading to the Ph.D. degree is offered within the School of Biological Sciences and the College of Medicine. Therefore, the degree title is “Doctor of Philosophy in the Biological Sciences with a Concentration in Experimental Pathology”. The program recruits students through the combined graduate training program in Molecular Biology, Genetics, and Biochemistry (MBGB). The MBGB program administers the first year curriculum. The application for this program can be found online. For questions about the application process, refer to the MBGB page under Application Procedure and Admission. Experimental Pathology is the study of disease, most notably human diseases and disease processes. While it is true that many programs at the University of California in Irvine have elements of their training program that pertain to human disease and disease processes, no single program makes the study of human disease the central tenet of its degree program.

Experimental pathology is an increasingly critical area of scientific research. While the National Institutes of Health has always maintained the importance of human health in its granting process, new technologies have made the study of human diseases ever more central to scientific discovery. Indeed, newer experimental approaches (e.g., transgenic mouse technologies) and knowledge bases such as the human, mouse and rat genomes, make studies on the molecular basis of human disease an exploding area of research interest and importance.

The graduate program in Experimental Pathology will feed new scientists into this ever-expanding area of human disease research. The aim of the program is to provide graduate students with the training necessary to become lead scientists studying the molecular bases of human diseases. Providing students with extensive training in molecular and cell biology, genetics, and biochemistry will prepare trainees for further concentration in Experimental Pathology. Therefore, this program will be a member of the combined graduate training program in MBGB. In the first year, students will be required to take the MBGB curriculum, existing of courses in proteins, nucleic acids, cell biology, and genetics. Students interested in Experimental Pathology will likely join the Experimental Pathology track within MBGB during the first year. With this strong foundation, students in the program will join the Pathology department in the spring or summer quarter of their first year. At this time, extensive study in human disease related research will begin in the laboratories of program faculty. Students will then have the opportunity to pursue further specialization of their training in areas including, but not limited to, neuropathology (mechanisms of neurologic disease), oncogenesis (mechanisms of human cancer), immunopathology (immunologic mechanisms of disease), molecular pathology (genetic basis of human disease), and infectious disease (molecular mechanisms of disease caused by viral, bacterial, fungal, and parasitic agents). The subsequent course work of students will include at least one didactic course per academic year concentrated in their area of research interest. These courses are outlined in greater detail below.

The objectives of this program are:

1. To provide students with the molecular and genetic knowledge necessary to understand the molecular bases of human diseases and to genetically manipulate organisms and/or cells to study these mechanisms.
2. To provide graduate students with sufficient understanding of known human disease processes to enable them to ask pertinent experimental questions to answer new and novel questions related to human disease and disease processes.
3. To provide the scientists of tomorrow, both academic and industry, with the knowledge necessary to address the important genetic and molecular causes of the most important diseases afflicting humans.

These objectives are unique among the programs within MBGB and within the University of California, Irvine.

II. THE PROGRAM.

1. Undergraduate Preparation for Admission.

Admission to the program will be through the combined program in Molecular Biology, Genetics, and Biochemistry. Therefore, students will be admitted by and into the MBGB program, rather than directly into this degree program concentration. As defined by the MBGB summary:

Applicants must have completed by the time of matriculation a baccalaureate degree, preferably emphasizing biological or physical sciences. Both the GRE General Test and an appropriate Subject Test are required. The prerequisite courses of general chemistry, organic chemistry, calculus, biology, physics, biochemistry, and genetics must have been completed or must be taken after admission. Admission will be based on an evaluation of the overall GPA, GRE scores, the applicant’s statement of purpose, letters of recommendation, and research background. The University requires a minimum undergraduate GPA of 3.0. Students with less than a 3.0 GPA can be admitted only on an exceptional basis, demonstrating evidence of strong motivation, maturity, and ability to profit from graduate education at the doctoral level.

2. Foreign Language Requirement.

The MBGB program has no foreign language requirement nor does the Ph.D. Program in Biological Sciences.

3. Program of Study.

1. Specific Fields of Emphasis-Biological Sciences with a concentration in Experimental Pathology.
2. Plan: Doctor of Philosophy degree.
3. Unit Requirements: All students must take at least one didactic course per academic year after year 1. Students must take additional units to be enrolled on a full-time status throughout their graduate training.
4. Required and recommended courses: Students will be enrolled in the combined graduate program in Molecular Biology, Genetics, and Biochemistry during the first year of the program.

Core requirements-year 1: Students will be required to take the following classes as part of the MBGB program:

Fall/Winter/Spring:
Basic Training (Dev. Bio 203)

Fall Quarter:
MolBio204-Structure and Functions of Proteins

Winter Quarter:
MolBio203-Structure and Biosynthesis of Nucleic Acids
AND: DevBio231B-Cell Biology
    or DevBio231D-Molecular, Cellular, & Developmental Neurobiology.

Spring Quarter:
MolBio206-Regulation of Gene Expression
    or MolBio207-Molecular Genetics
    or DevBio210-Developmental Genetics.

Students are also required to do two laboratory rotations in two different laboratories during the first year. The requirement for two different laboratory rotations may be waived for students in the Medical Scientist Training Program. Students are encouraged to do at least three rotations in laboratories that provide exposure to diverse research topics and a wide variety of experimental approaches. Such varied research opportunities provide a rewarding academic experience. Students select a thesis mentor and laboratory at the completion of the Spring Quarter in the first year and begin work to complete a Ph.D. thesis based upon their own original laboratory research.

In addition, students who choose to join the program leading to a Ph.D. in Biological Sciences with a concentration in Experimental Pathology will be required to take two courses in Experimental Pathology: PATH225: Molecular Mechanisms of Human Disease and PATH226: Animal Models of Human Disease (under development). These courses will be offered every other year in alternating years. These courses may be taken at any time during the course of the student’s training but will likely be completed in the first two or three years of the program.

Core-elective courses: From the following list, and any other core-elective courses suggested by participating faculty and approved by the faculty of the track, each student will take at least one core-elective in the first year and complete a total of two core-electives by the end of the second year. Students will be required to take a minimum of one didactic core-elective course for five years of graduate training. In the case of completion of all graduate requirements prior to five years, no additional coursework will be required. After five years, no additional didactic course work will be required. Path 230-236 are new courses derived from the medical school pathology course.

Biochem212: Signal Transduction and Growth Control
DevBio231B: Molecular, Cellular & Developmental Neurobiology (if not taken year 1)
MolBio217A: Cancer Biology I
MolBio217B: Cancer Biology II
MolBio218: Clinical Cancer for Basic Scientists
M&MG215: Molecular Immunology
Path221/M&MG221: Immunopathogenic Mechanisms of Disease
Path222/M&MG222: Molecular Pathogenesis of Viral Infections
Path225/M&MG225: Molecular Mechanisms of Human Disease
Path230: Principles of Experimental Pathology
Path231: Pathology of Cardiovascular Diseases
Path232: Pathology of Pulmonary Diseases
Path233: Pathology of Renal Diseases
Path234: Pathology of Gastrointestinal Diseases
Path235: Pathology of Genitourinary Diseases
Path236: Graduate Neuropathology
Path271A: Molecular Physiology & Disease

Throughout the training program, students who have chosen to do their thesis research under the Experimental Pathology concentration are required to enroll in PATH 200 for research credit, under their research advisor, and PATH 203, a literature review course. Students will also participate in the Pathology department research seminar series, which has research in progress presentations from faculty, postdoctoral fellows, and graduate students. This seminar series currently meets twice monthly. As the graduate program grows, the seminar series will become more frequent.

Teaching Component: Per the MBGB Program-all students in the MBGB program are required to teach during their first and second year of study. Students enroll in MolBio399 (University Teaching) and teach in either undergraduate lecture or undergraduate laboratory courses within either the Department of Developmental and Cell Biology or Molecular Biology and Biochemistry. In general, students are teaching assistants in a total of three courses. Previously, teaching assistant activity has been entirely in year two of the students’ graduate program. More recently, students begin by teaching in the Spring Quarter of their first year and, additionally, in the Fall and Winter Quarters of their second year. This is arranged by MBGB in coordination with the respective departments. As students in Experimental Pathology will be MBGB students, all students in Experimental Pathology will be subject to the same teaching requirements as other MBGB students.

4. Qualifying Examinations.

Students in MBGB are required to pass both a written and oral qualifying examination in the summer following the first year of graduate school. This examination consists of an NIH-style grant proposal on a topic related to but separate from the thesis research. The student’s thesis advisor in consultation with the qualifying examination committee selects the topic of the proposal. The student’s research advisor from the faculty in MBGB, currently in excess of 145 faculty members, will form the qualifying examination committee. The committee will be composed of a chair and two at-large members. The student’s thesis advisor cannot be one of the three members. After assignment of a topic, the student has four to six weeks to prepare a NIH style grant proposal consisting of ten, double-spaced pages. The committee will review the proposal and the student will present a 45-minute oral presentation documenting the experimental approach and answering questions posed by the committee. Based on the oral and written examinations and the grades of the student in the first year, the committee will confer a qualifying examination score of pass, provisional pass, or fail. If a failure occurs, the student will be provided with a course of remediation. Students who fail the examination are given a second opportunity through a second administration of both oral and written components. If a student fails the preliminary examination a second time, a recommendation will be made to the Dean of Graduate Studies to academically disqualify the student from graduate study. The committee will determine remediation of “provisional pass”. After remediation, a recommendation of continuation in the program or dismissal from the MBGB program will be made to the director of the program.

5. Thesis and Dissertation.

During the second year of the program, students will begin thesis research in the laboratory of faculty within Experimental Pathology. Once sufficient research progress has occurred, usually within the second year in Experimental Pathology (third year in the graduate program), the student will Advance to Candidacy. The student will prepare a twenty-five page written proposal for dissertation research and orally defend this proposal before the Advancement to Candidacy Committee. This committee will consist of five faculty members, one of whom must be outside the School of Biological Sciences, at least one additional member must not hold an appointment in the Department of Pathology and at least two, including the thesis mentor, must hold appointments in the Department of Pathology. After successful Advancement to Candidacy, a Doctoral Committee will be formed, selected from the Advancement to Candidacy committee. The composition of this committee will be at least three members, a majority of which must be from the Department of Pathology. All five members of the Advancement to Candidacy committee can be selected to the dissertation committee. The purpose of the committee is to guide the student’s progress towards completion of the dissertation. When the student’s thesis advisor and the remaining members of the Doctoral Committee determine that a sufficient body of original research has been completed, the student will prepare the thesis for a public defense before the Doctoral Committee.

6. Final Examination.

The student’s oral defense of the dissertation before the doctoral committee constitutes the final examination.

7. Sample Program.

Due to the number of electives and the diverse nature of Experimental Pathology training, no set program will exist. For example, some students may choose a heavy emphasis on neuropathology, with elective courses in neuroanatomy, neurological development, and neuropathology. Other students may specialize in the pathogenesis of cancer with a heavy emphasis on genetics, cell signaling, and cell and cancer biology. Nevertheless, a general program overview can be offered as demonstrated below.

Year 1 (As determined by the MBGB Program):
Fall Quarter: MolBio204-Structure and Functions of Proteins and a laboratory rotation.
Winter Quarter: MolBio203-Structure and Biosynthesis of Nucleic Acids and DevBio231B-Cell Biology or DevBio231D-Molecular, Cellular, & Developmental Neurobiology and a laboratory rotation.
Spring Quarter: MolBio206-Regulation of Gene Expression or MolBio207-Molecular Genetics or DevBio210-Developmental Genetics and MolBio399-University Teaching and a laboratory rotation or the student begins research in the laboratory of the thesis advisor.
PATH225: Molecular Mechanisms of Human Disease.
As PATH225 and PATH226 are to be offered in alternating years, some students will take PATH226 followed by PATH225.
Summer Quarter: Qualifying examination.

Year 2:
Fall Quarter: MolBio399-University Teaching; PATH200-Research in Experimental Pathology; PATH203-Advanced Studies in Experimental Pathology; PATH204-Seminars in Experimental Pathology.
Winter Quarter: MolBio399-University Teaching; PATH200, PATH203, PATH204.
Spring Quarter: PATH200, PATH203, PATH204, and PATH226: Animal Models of Human Disease (Under Development)/or PATH225: Molecular Mechanisms of Human Disease.

Year 3:
Fall Quarter: PATH200, PATH203, PATH204.
Winter Quarter: PATH200, PATH203, PATH204.
Spring Quarter: PATH200, PATH203, PATH204.
Fall, Winter, or Spring Quarter: One elective course.
Summer Quarter: Advancement to Candidacy.

Year 4:
Fall Quarter: PATH200, PATH203, PATH204.
Winter Quarter: PATH200, PATH203, PATH204.
Spring Quarter: PATH200, PATH203, PATH204.
Fall, Winter, or Spring Quarter: One elective course.

Year 5:
Fall Quarter: PATH200, PATH203, PATH204.
Winter Quarter: PATH200, PATH203, PATH204.
Spring Quarter: PATH200, PATH203, PATH204.
Fall or Winter: One elective course.
Spring Quarter: Dissertation Defense.

8. Normative time from matriculation to degree.

The normative time from matriculation to completion of the Doctoral degree will be five years (before the beginning of the 16th academic quarter*). The first year will be in the MBGB program and the remaining four years in the Department of Pathology doing thesis work in the laboratory of Experiment Pathology faculty. Students may also perform thesis work in the laboratories of affiliate faculty, currently including faculty from the Departments of Molecular Biology and Biochemistry, Physiology and Biophysics, and Biological Chemistry. The second year is officially in the MBGB program, of which University teaching is the principle MBGB activity. As indicated above, the normative time from matriculation to advancement to candidacy (i.e. pre-candidacy) will be three years (before the beginning of the 10th academic quarter) and the normative time to the Ph.D. in candidacy, two years. All students will be required to defend their theses by the end of their seventh year (before the beginning of teh 22nd academic quarter).

*The 10th academic quarter would be the beginning of the fourth year, so normative time to advancement would be during the third year of graduate school, including the summer of the third year. Similarly the 16th and 22nd academic quarters would be before the beginning of the 6th and 8th years.

III. COURSES

1. Courses Offered in Pathology.

PATH200: Research in Experimental Pathology - Taught by Pathology Faculty.

PATH203: Advanced Studies in Experimental Pathology - Taught by Pathology Faculty.

PATH204: Experimental Pathology Research Seminar - Attendance and participation in the departmental research seminar series.

PATH 225: Molecular Mechanisms of Human Disease. Taught by W.E. Robinson, Jr., MD, Ph.D. Joint listed as MMG225. 3 units, Spring quarter in odd numbered years..

PATH 226: Animal Models of Human Disease. To start Spring 2006, To be joint listed as MMG226. 3 units, Spring quarter in even numbered years..

PATH 230D: Principles of Experimental Pathology - Taught by the faculty of the Department of Pathology. 4 units, Fall quarter.

PATH 231A: Pathology of Cardiovascular Diseases - Taught by the faculty of the Department of Pathology. 2 units, Fall quarter.

PATH 232A: Pathology of Pulmonary Diseases - Taught by the faculty of the Department of Pathology. 1.5 units, Fall quarter.

PATH 233A: Pathology of Renal Diseases - Taught by the faculty of the Department of Pathology. 1 unit, Fall quarter.

PATH 234A, 234B: Pathology of Gastrointestinal Diseases - Taught by the faculty of the Department of Pathology. 2 units, Fall through Winter quarters.

PATH 235A, 235B: Pathology of Genitourinary Tract Diseases - Taught by the faculty of the Department of Pathology. 2 units, Fall through Winter quarters.

PATH 236B: Graduate Neuropathology - Taught by the faculty of the Department of Pathology. 1.5 units, Winter quarter.

PATH 271A: Molecular Physiology & Disease.

NB: PATH230-236 are sections of the second year medical school pathology course, 508B. Graduate students may take portions of the course for credit as indicated by these new courses. The students will, in addition to attending the class sections, work in small groups with a faculty member and will discuss experimental approaches to the medical problems taught in the course. Each student will submit written hypotheses, aims, and experimental approaches relevant to four pathologic problems. Student evaluations will be made based on attendance, students’ participation in the discussions and the quality of their written experimental plans.

2. Supporting Courses.

MBB204-Structure and Functions of Proteins
MBB203-Structure and Biosynthesis of Nucleic Acids
DC231B-Cell Biology
DC231D-Cellular, Molecular, & Developmental Neurobiology.
MBB206-Regulation of Gene Expression
MBB207-Molecular Genetics
MMG215-Molecular Immunology
MMG221-Immunopathogenic Mechanisms of Disease
MMG222/PATH222-Molecular Pathogenesis of Viral Infections
DB210-Developmental Genetics
MBB399-University Teaching
BC212-Signal Transduction and Growth Control