Curriculum, PhD in Molecular & Cellular Basis of Disease (Experimental Pathology)


INTRODUCTION

The Molecular and Cellular Basis of Disease (MCBD) PhD program is designed to rigorously train students to excel in the research associated with elucidating the mechanisms of disease processes, with a particular emphasis on the skills necessary to perform translational research. Admission to the MCBD program is in most cases through the combined Molecular Medicine (Pathology Pharmacology, and Physiology) (MM/PPP) admissions program, or through the Medical Scientist Training Program (MSTP). Students from other BIMS programs would be accepted into the MCBD PhD program.


COURSEWORK

FIRST YEAR-- The focus of the first year of studies is on core curriculum requirements that are shared by most programs (e.g. MolMed - MOMD, MII, BMBG, CDB) at UVA. Generally, the equivalent accomplishments will be achieved during the first two years of medical education within the MST Program.

First Semester:

A total of at least 24 credit hours should be earned during the first year.

Combined Core Curriculum- 

(1) Cell Structure and Function (BIMS 512) All need number of credit hours,
(2) Gene Structure, Expression and Regulation (BIMS 811)
(3) Macromolecular Structure and Function (BIMS 503)

Molecular Basis of Human Disease (BIMS 813) This is a series of joint lectures by basic and clinical scientists that focuses on the clinical context of a specific biomedical problem and the contemporary research that has resulted in major advances and treatment of the disease.
Orientation-The department of Pathology will organize a tour or meeting with the first year students within their first month into the MM/PPP program

Second Semester:

Molecular Basis of Human Disease (BIMS 814) - The continuation of BIMS 813
Grad Physiology (BIMS 832) is a required course.

Electives - Students are required to take ONE elective from the following: Pharmacology, Practical Molecular Medicine, Genetics, Molecular Pathogenesis, Immunology, Molecular Basis of Carcinogenesis, Vascular Biology, Neurophysiology, Development and Reproduction or others as relevant to their area of interest.
Research Ethics (BIMS 710) - Students are required to take research ethics course.
Research Rotations (First and Second Semester)

Generally, students complete 3 laboratory rotations (BIMS 843, 844 up to 12 credit hours; 4 credit hours/per lab rotation) in different laboratories in their first year, as required by their admission program. By April 29 of their first year students are expected to select their research mentor and choose the department from which they will receive their degree.


SECOND YEAR-- During the second year, students have three main tasks:

1) Identify members of a thesis committee
In consultation with the Mentor, the student will select a committee of four or five faculty members who will serve as guides and readers of the qualifying examination and thesis. The student's thesis committee must consist of the mentor and three or four other expert scientists.

* The Chair of the Thesis committee must be a Full Member of the training faculty of MCBD, and a faculty member of the Department of Pathology, but cannot be the research Mentor.

* At least two members of the Thesis Committee must be Full Members of the training faculty of MCBD, and at least one must be a trainer in another Biomedical Sciences training program outside of MCBD/Pathology.

* Generally, one member should be an outstanding scientist with expertise outside the student's area of research interest.

2) Take advanced electives and participation courses related to the Molecular and Cellular Basis of Disease-

Twenty credits must be completed during this year to satisfy the total requirement for the PhD, in addition to the 24 credits earned during the first year. Normally, no for-credit courses are allowed in the third year, so required coursework must be completed during the second year.

Advanced Electives: Students must complete at least 12 credit hours of didactic courses relevant to their interests and the Molecular and Cellular Basis of Disease. At least one of these courses must be BIMS 857/858(Topics in Medical Pathology) or BIMS 807(Rotation in Pathology). Other didactic electives from Pathology or other Programs may be taken in addition. Didactic courses must be approved by the Program Director or Curriculum Director.

Required Participation activities: Students must enroll and regularly attend BIMS 850 (PRPR) and BIMS 845/846 (Pathology Department Research Seminar). In addition, students must identify and participate in a topical journal club relevant to their research interests, or relevant to their training grant. In the case that no pre-existing journal club is available, BIMS 847/848 may be used to organize a special readings program.

Other opportunities to supplement basic science training activities include workshops to promote skills in translational research, including Patents/Intellectual Property, Grant Writing/Review and others.

 

Course list (MCBD courses listed only)

BIMS 857, 858 Topics in Medical Pathology: Students select subtopics of the Medical Human Pathology course. 3 Credit Hours per semester.

BIMS 807 Rotation in Pathology: A four week rotation in several facets of Anatomic and Clinical Pathology. 4 Credit Hours. Probably needs Spring number too.

BIMS 847, 848 Research Correlation in Medical Pathology Self-organized journal club. 1 credit hour per semester. Participation in other organized journal clubs is encouraged when available.

BIMS 845, 846 Pathology Department Seminars: Tuesday Noon research seminar 1 credit hour/semester (AP Conference Room, New Hospital Expansion BLDG, Third Floor, Room 3025).

BIMS 849, 850 Pathology Research Progress Report: Bi-weekly seminar series for trainees to present their research progress (Location: MR5, Third Floor, Room 3005).
BIMS 997 Non-topical research: for students who have not completed their advancement to candidacy - variable credit up to 12 hours/semester.

BIMS 999 Non-topical research: for students who have completed their advancement to candidacy - variable credit up to 12 hours/semester.

3) Prepare for completion of the Qualifying Exam
In consultation with the student's mentor, the student will prepare for the Qualifying Exam, which consists of writing an NIH-style grant on the proposed thesis work. This Exam, specified in more detail elsewhere, will consist of a written document between 18 and 20 pages in length (double spaced) which will be defended orally before the thesis committee. The Exam should present a logical, achievable research plan for the Thesis, outlining the biological problem with a relevant literature review, and providing literature evidence and preliminary laboratory results that demonstrate the achievability of the project. The Qualifying exam must be presented by September of the Third Year.

SUBSEQUENT YEARS -

The focus of subsequent years will be on laboratory research oriented toward the selected thesis topic. Students will spend more time in the lab developing their thesis project. Students should plan on completing their thesis within a 5-year time frame, meaning within 4 years after selection of their mentor. Students are expected to publish their findings in high quality peer-reviewed journals. At least one research paper as a first author on the thesis research should be accepted for publication before defense of the Thesis.

Continued participation in the research activities of the Program and Department is expected, specifically regular attendance at PRPR, Pathology Research Seminar, the chosen Journal Club, and the annual Pathology Research Retreat. Financial support of the student from the Department is contingent upon adequate participation in these activities and suitable progress in the student's thesis research.

The Thesis Committee must meet at least annually through the term of the training. Under certain circumstances the Graduate Director may require more frequent Thesis Committee meetings and/or specific progress objectives from the student. The Graduate Director must be informed of the time of meetings, and at his discretion may attend the meeting at a mutually convenient time, and may participate as a voting member of the Committee. Thesis committee meetings should be documented by the Committee Chair by email communications with the student, mentor, committee members, and graduate program administrator.

Graduation requirements include a written thesis that conforms to University specifications, a closed oral defense of the document and research conclusions, and a public oral defense (seminar presentation). The written thesis document should include an adequate background information chapter and a chapter outlining future directions for the research.


BIMS 857, 858 - Topics in Medical Pathology- (3 Credit Hours)
From the Medical course in Human Pathology, students will select General Pathology (required) and three other subtopics based on their research program, summing to at least 45 hours of in-class time. 3 credit hours per semester.

1.  General Pathology (10 hours in-class time)
2.  Pulmonary Pathology (15 hours)
3.  Dermatopathology, Bone, Toxicology, Endocrine (6 hours)
4.  Gastrointestinal Pathology (12 hours)
5.  Cardiovascular Pathology (9 hours)
6.  Breast and Reproductive Pathology (4 hours)
7.  Renal Pathology (12 hours)
8.  Hematopathology (30 hours)
9.  Neuropathology (15 hours)
10. Microbiology and Forensic Pathology (10 hours)


COURSE DESCRIPTIONS
 
BIMS 807 - Rotation in Pathology - (4 Credit Hours)
Generally Fall only, since scheduling is more difficult in Spring- Students will spend 4 weeks, selecting from 3 or 4 Pathology Sections. These rotation will expose students to clinical problems and hands-on techniques such as tissue procurement, processing and diagnosis. Students will attend Clinical Conferences in which cases of human diseases related to the students' areas of thesis research are discussed. Discussions focus on the etiology of the disease, its stage, progression, and clinical treatment. The purpose of attending such clinical conferences is to develop a full appreciation of the major issues that characterize a specific disease and to provide an understanding of how the current means of disease treatment could be improved by advances in cellular or molecular therapeutics. This rotation will allow students to utilize clinical faculty members as resources to further discuss the relevance of their thesis research to the understanding of human disease. Students are encouraged to select one of these faculty members as member of their thesis committee.

Sections
1. Hematopathology (Dr. Goldfarb)
For the rotation in Hematopathology, the student will attend the daily diagnostic sessions known as "signout". These sessions encompass analysis of blood, bone marrow, and lymph node specimens by light microscopy. Additional signout sessions are held for flow cytometric analysis of similar specimens. The student is expected to gain an understanding of the basic morphology of normal blood, bone marrow, and lymph nodes. In addition the basic principles of multiparametric flow cytometric analysis of samples will be covered. The student is also expected to develop a basic understanding of the molecular abnormalities underlying leukemia and lymphoma. Correlations will be made the fundamental questions being addressed in current research on normal and malignant hematopoiesis. Clinical hematology journal club occurs weekly. Basic science lab meetings occur weekly with presentation of work in progress and discussion of cutting edge articles.

2.  Neuropathology and Autopsy (Drs. Lopes and Mandell)
Students participate in the diagnostic service of the Division of Neuropathology, which includes the examination of intra-operative consultations (brain smears and frozen sections) and permanent sections of neurosurgical specimens, the gross and microscopic examination of brains obtained from the autopsy material in the Department, and gross and microscopic examination of muscle and nerves. Students essentially function as residents in studying at first hand the neuropathological material under the guidance and supervision of a faculty member, and participate in the regular weekly microscopic conference in which current neuropathological material and consultation case material submitted from outside centers are reviewed and discussed. In addition, the students participate in the interdepartmental conferences with the Neuro-Oncology Center team of clinicians and neurosurgeons. Projects in clinicopathologic correlation and/or experimental neuropathology may be possible during this rotation by pre-arrangement.

3.  Clinical Microbiology and Microbial Pathogenesis (Dr. Hazen)
This rotation is designed to familiarize the student with microbial pathogenesis from the "bench to the bedside". Students will attend daily "plate rounds" in Clinical Microbiology during which diagnostic interpretations are considered. Attendance of the Infectious Diseases attending rounds at least twice per week and Infectious Diseases case conference is required. Students are expected to become familiar with biochemical, morphologic, serologic, and molecular methods used for diagnosis of infectious diseases and for evaluation of antimicrobial efficacy. During the rotation, students will become acquainted with microbial virulence mechanisms that contribute to progression of bacterial, fungal, and viral infections.  Mechanisms of inducible and intrinsic antimicrobial resistance will also be covered. Ongoing basic science questions about microbial pathogenesis and host response addressed in current research will be discussed. Research lab meetings involving presentations of work in progress and review of current literature are held weekly.

4.  Immunology and Renal Pathology - Renal disease mechanism in the clinical setting (Drs. Tung and Cathro)
Students will learn the clinicopathologic presentation of the following diseases based on case studies: The Alport syndrome; Goodpasture's disease; Glomerulonephritis of systemic lupus erythematosus; Renal allograft acute rejection. Students will learn the following concepts and techniques:  Pathophysiological basis for the clinical presentations; Introduction to histology and histopathology of kidney and inflammation; Electron microscopy and ultrastructural findings of immune complexes; Immunohistology and appearance of immune complexes. Finally, students will learn the disease mechanism pertaining to each disease by addressing the following issues or questions: Biochemistry of glomerular basement; Why do autoantigens stimulate autoantibody response?  How is self tolerance maintained and terminated?  How do autoantibodies mediate tissue injury and disease?  How do antigens stimulate allogeneic T cell response? What are the mechanisms of renal allograft rejection? Read a good review on each topic, following by discussion. Students are expected to participate in the diagnosis of ongoing renal biopsy cases.

5.  Molecular Diagnostics (Drs. Mahadevan and Silverman).
This rotation is designed to get the students familiar with various aspects of molecular diagnostics. The application of molecular diagnostics to infectious diseases, genetic diseases, and hematopathology will be emphasized. Students will attend weekly laboratory meetings and clinical genetics conferences. They will also have an opportunity to become familiar with the cytogenetics laboratory and will have an opportunity to generate a karyotype. Students are expected to become familiar with the fundamentals of molecular genetics, real-time PCR and quantitative RT-PCR, DNA sequencing, automated fragment analysis, Southern blotting, etc. They will get exposure to the issues of genetic counseling. In addition, they will get an opportunity to understand and interpret HIV genotyping, fragment analysis as it applies to identifying clonal processes and genetic disorders. Emphasis will be placed on the underlying molecular basis of the various disorders and genotype-phenotype correlations.

6. Surgical Pathology (Drs. Iezzoni and Moskaluk)
The purpose of this rotation is for the student to gain an understanding of the role of microscopic examination and special techniques in the diagnosis and study of human disease. Accordingly, the student will attend daily "sign-out" sessions, during which patient tissue specimens from the clinical Surgical Pathology service are examined microscopically, discussed and diagnosed. These clinical specimens demonstrate a diverse variety of neoplastic and non-neoplastic human diseases. Also, the student will attend weekly Surgical Pathology and Autopsy conferences, where clinical cases are presented and discussed in detail. In addition, the student will rotate through the clinical and research Surgical Pathology laboratories to gain exposure to a variety of the special techniques used in diagnostic and investigational pathology, specifically tissue procurement, tissue processing, immunohistochemistry, microdissection, and microarray analysis. Upon completion of this rotation, the student will have gained an appreciation for the role of microscopic examination and special techniques in the diagnosis and investigation of human disease.

7. Clinical Chemistry/Biochemistry, Toxicology/Therapeutic Drug Monitoring and Medical Informatics (Drs James Boyd, David Bruns and Dede Haverstick)
Testing done in these areas of the laboratory provides the largest portion of diagnostic results in medicine. The rotation will address (a) the types of clinical questions that can be answered by chemical and biochemical measurements, (b) the performance of those measurements, and the reporting and (c) the interpretation of the results of the tests. Thus, the rotation will first provide an introduction to the principles of formulating clinical questions that can be addressed by laboratory testing and the principles of formulating these questions. Next we will explore principles of analytical science (what we should have learned in chemistry class, had we been paying attention - in two easy lessons) and examples of modern measurement techniques used in the care of patients and in monitoring of health status. This will include a laboratory tour to see the automation and robotics in current use. We will then address the interpretation of clinical laboratory data in individual patients. This will be done by use of discussion, readings and examples. In the various areas of this rotation (a through c), we will use examples from clinical toxicology, therapeutic drug monitoring, clinical chemistry and clinical biochemistry, including biochemical genetics and tests of endocrine signaling.


GENERAL EXPECTATONS

Students are expected to attend and participate in research activities and seminars in the Department of Pathology. These include a bi-monthly Research in Progress that focuses on student research presentations, weekly departmental seminars, a Welcome lunch to meet faculty members and other trainees in the department and an annual research retreat with oral and poster presentations.