2009 Spring Semester

BIOM 502 Molecular Basis of Disease
INSC 600-012 Neurobiology of Disease: Neurodegenerative Diseases I

COURSE DESCRIPTION AND SYLLABUS

Course Directors
Carolyn Cambor, MD; 215-614-1428 (Carolyn.Cambor@uphs.upenn.edu)
Mitch Lewis, DPhil, 215-898-0949  (lewis@mail.med.upenn.edu)

Time: 8:30 – 10:00 am, Tuesdays and Thursdays, Spring Semester, 2009

The first part of this course runs concurrently with INSC 600-012, Neurobiology of Disease and ends with Spring break.

The second part of this course begins after Spring Break, during the week of March 16, 2009 and ends April 28, 2009.

Location: Barchi Library, Room 140 John Morgan Building

Textbook: None. Review videos and papers will be assigned before each class session.

Students should note that a review video will be assigned before the first class.

 

Part 1 of the BIOM 502 Course / INSC 600-012
Our understanding of the most common neurodegenerative disorders has advanced considerably over the past 10 years. Not only are the pathophysiological mechanisms increasingly understood, but many candidate genes have been identified and are the subjects of intense investigation. This class will use faculty presentations, readings of review publications and video resources and to discuss the major pathological mechanisms and genetics of Alzheimer’s Disease, Parkinson’s Disease and ALS, amyotrophic lateral sclerosis. We will focus on recurring themes (protein aggregation, production of reactive oxygen species, genetic risk modifiers, glutamate toxicity) as well as differing mechanisms among diseases. This course also will address the significance of tau in multiple neurodegenerative diseases and the role of the recently identified protein TDP-43.

 

Part 2 of the BIOM 502 Course
During the second half of the BIOM 502 course, several non-neurologic diseases will be studied emphasizing the mechanisms underlying the diseases, the clinical presentation of the diseases and how this information impacts the approaches to treatment as well as current and future research efforts for each disease. This part of the course will study inflammatory and neoplastic diseases of the GI tract (inflammatory bowel disease & colon cancer), diabetes mellitus and chronic myelogenous leukemia.

 

Goals

Specific goals will be identified for each session and included in the syllabus

Lectures will commonly cover

  • clinical presentation and epidemiology (~10 min)
  • physiological and pathophysiological mechanisms, including biological mechanisms in common with other diseases/ disorders/ conditions  (40-45 min)
  • current therapies AND/OR strategies for developing future therapies: the role of “translational research”; design and conduct of patient-oriented research AND/OR any relevant ethical issues in clinical research, and/or ethics of particular clinical trial designs in specific patient populations (~10 min)

Faculty

The faculty represent a range of departments and expertise in the basic science and clinical aspects of the disorders to be covered. Faculty will lecture and/or participate in the discussion of papers.

Class format

Typical class format

45-60 min faculty lecture, followed by 30-45 min for student presentation, or for discussion of assigned paper or video. Lecturers will facilitate the discussion. During this time the posted student questions about the assigned review paper or video will be addressed (see “requirements and grading”.)

Class format on student presentation days: During the last few class sessions prior to Spring break and again at the end of the course, students will present primary research papers to the group (see “requirements and grading”.)

Requirements and grading

In addition to course attendance, the following are expected of the students:

a)  Class preparation: students will watch an introductory video or read a textbook chapter or review paper in advance of each class.

b)  Submission of discussion questions: students must submit, via the electronic bulletin board, two questions about each assigned video or paper. Questions must be posted to the electronic bulletin board at least 3 hours in advance of the session for which the video or paper is assigned; questions will be used as the basis for in-class discussions that follow the lecture. Students must submit questions for 10 out of the 12 course sessions and for all sessions during which students will be presenting primary research papers. These questions must be submitted to the electronic bulletin board 24 hours in advance of the course session for which they are assigned so that the presenting students can incorporate answers into their presentation.

c)  Consistent participation in the discussions that follow each lecture: Level of questions is not as important as active participation.

d)  Quality of presentation: each student will make one ~20 minute presentation during the last week of the course. The papers which will be presented will be assigned at last 1 week in advance and students will work in pairs or groups to prepare and present their paper(s). Each presentation is expected to address: background, description of materials and methods used, results, conclusions, questions the study answered and those it left unanswered, critique and/or questions for discussion, possible future directions. Presentations and/or presenters should address during their presentation the questions submitted by the other students.

2009 Schedule

Part 1

Week

Date

Lecturer

1

Thursday, January 15
Clinical presentation of AD; diagnostic criteria; AD biomarkers: biochemical and imaging
Student preparation: AD video (give link)

Steven Arnold, MD

2

Tuesday, January 20
AD Genetics
Student preparation: review paper (give ref)

Virginia M.Y. Lee, PhD

Thursday, January 22
Protein misfolding as a common mechanism among many neurodegenerative disorders; Overview of clinical trials in AD (inclu. which pathophysiological mechanisms were targeted)
Student preparation: review paper (give ref)

Virginia M.Y. Lee, PhD

3

Tuesday, January 27
Mechanisms of AD pathogenesis and pathophysiology, e.g. amyloid cascade hypothesis, tau, and the therapeutic approaches they suggest. Review of recently completed clinical trials and of the NSAID (non-steroidal anti-inflammatory) trial.
Student preparation: review paper (give ref)

John Trojanowski, MD, PhD

Thursday, January 29
Tau: involvement in AD and FTD (fronto-temporal dementia). Potential tau and tau-related (e.g. MT stabilizing, kinase inhibiting) therapeutics.
Student preparation: review paper (give ref)

Virginia M.Y. Lee, PhD

4

Tuesday, February 3
Clinical overview of FTD and ALS
Student preparation: FTD and/or ALS video (give link)

Murray Grossman, MD

Thursday, February 5
TPD43: a newly identified pathological protein in sporadic ALS. Pathology, pathological mechanisms, genetics; imagining a “bench to bedside” story…
Student preparation: review paper (give ref)

Virginia M.Y. Lee, PhD

5

Tuesday, February 10
Glutamate toxicity and the role of glutamate transporters. Examples of glutamate modulators as therapeutic agents.
Student preparation: review paper (give ref)

Mike Robinson, PhD

Thursday, February 12
Parkinson’s Disease: Clinical overview and review of clinical trials
Student preparation: PD video (give link)

Andrew Siderowf, MD

6

Tuesday, February 17
Parkinson’s Disease: pathological mechanisms; review of mechanisms upon which clinical trials / medications have been based: e.g. antioxidants (monoamine oxidase B inhibitor, Co Q10 etc); dopamine agonists, Catechol-O-methyl transferase (COMT) inhibitors, NMDA receptor antagonists…
Student preparation: review paper (give ref)

Benoit Giasson, PhD

Thursday, February 19
Parkinson’s Disease: genetics – alpha synuclein, parkin, DJ1, PINK1, and LRRK2. Gauchier’s mutations … Gene therapy for PD.
Student preparation: review paper (give ref)

Vivianna Van Deerlin, MD, PhD

7

Tuesday, February 24
Oxidative stress: Role across various neurodegenerative disorders and role as potential therapeutic agents.
Student preparation: review paper (give ref)

Harry Ischiropolous, PhD

Thursday, February 26
Student Presentations

8

Tuesday, March 3
Student Presentations

Thursday, March 5
Student presentations

Part 2

Week

Date

Presenter

Inflammatory & Neoplastic Diseases of the Colon

1

Tuesday, March 17
Inflammatory Bowel Disease

Emma E. Furth, MD

Thursday, March 19
Inflammatory Bowel Disease

Emma E. Furth, MD

2

Tuesday, March 24
Cancers of the GI tract

Emma E. Furth, MD

Thursday, March 26
Cancers of the GI tract

Emma E. Furth, MD

Diabetes Mellitus

3

Tuesday, March 31
Glucose metabolism; normal pancreas anatomy & histology

Mitch Lewis, DPhil
Carolyn Cambor, MD

Thursday, April 2
Pathophysiology & clinical presentation of diabetes

Serena Cardillo, MD

4

Tuesday, April 7
Research articles TBA

Mike Rickels, MD

Thursday, April 9
Research articles TBA

Mike Rickels, MD

Chronic Myelogenous Leukemia

5

Tuesday, April 14
Background & mechanisms

Martin Carroll, MD, PhD

Thursday, April 16
Approach to treatment & research

Martin Carroll, MD, PhD

Student presentations

6

Tuesday, April 21

TBA

Thursday, April 23

TBA

7

Tuesday, April 28

TBA