ALS 301: Molecular Basis of Disease
The list of diseases with known molecular basis includes infectious diseases, cancers, metabolic diseases and mental health diseases. The idea that some diseases are due to genetic causes, a demonstration of which dates back to the early 20th Century, has now been expanded to include the possibility that all recognized human disorders may involve one or more genetic components of the patient. Since the genetic or epigenetic (in the case of identical twins) endowment of every human being on earth is different we must take seriously the concept of personalized medicine. This course examines the role of genes, proteins and RNA in causing or combating diseases, and emphasizes the current conceptual and analytical tools that are brought to bear, and their limitations, on our understanding.
The first part of the course examines infectious diseases and concept of complex diseases. Using specific case histories, we will critically examine the landmark efforts currently underway in discovering the genetic basis of diseases. We will specifically explore contributions by several new biotechnology advances, including whole genome sequencing and genome-wide association studies. Specific case studies will include certain infectious diseases, and several cancers.
The second part of the course will examine the importance of biomarkers in typing diseases and for future personalized medicine. Discussions will be centered on involvement of the innate and adaptive immune systems in causing chronic inflammation in several autoimmune diseases and cancer.
The third part of the course will examine cardiovascular diseases, rare diseases, and the potential of stem cell therapeutics. Using hypertension as an example, students will learn about the systematic development of drugs to treat hypertension based on the rennin angiotensin system. Cell and stem cell therapies will be discussed in the context of diabetes and heart failure. Gene therapy will be taught from the perspective of rare diseases of genetic origin. Lastly, future therapies involving siRNA, microRNA and gene modification will be presented and debated.
There is no textbook for this course. Required readings are drawn from a collection of review articles and original papers available from Sakai at the course site. There may also be a few reference books, which will be held on reserve at the KGI library.
The fourth part will examine several neurodegenerative diseases, including CAG repeat diseases, Alzheimer's disease, and prion diseases.
Molecular networks in normal and diseased cells; signaling pathways; genome wide expression measurements for revealing disease mechanisms; genome-wide association studies; the role of gene mutation, miRNA and protein degradation in specific diseases; virus-host interaction in hepatitis C and influenza; lung cancer; breast cancer; colorectal cancer; melanoma; Celiac disease; Wegener's Granulomatosis; Diabetes; Myeloproliferitive Neoplasms; Huntington's disease; Parkinson's disease; Alzheimer's disease; prion diseases; Hypertension, Heart failure, Diabetes types 1 and 2, transplantation of stem cells, gene therapy and rare diseases.
- Developing the perspective that gene-gene interactions are the basis of most human diseases
- Evaluate current methods for identifying disease networks
- Developing a sense of the limitations of current tools and understanding
- Understand the complexities of certain diseases and appreciate how genetic variations influence disease outcomes
- Understand the roles of innate and adaptive immune systems in several diseases
- Understand how use of nucleic acid, protein and cellular biomarkers can improve outcomes, in terms of patient well being and a lower cost of care, for many diseases
- Be able to discuss traditional drug therapy in comparison to new gene and cell therapies in various diseases
Class participation: 20%
Midterm Exam: 20%
Final group project presentation: 20%
Project report: 40%