BIO 170c Conference course in human biology, skip to content

Semester / Unique Number:

Spring 2014 / 50515

 
Regenerated bladder

 

Medical applications of iPS cells. Reprogramming technology and iPS cells have the potential to be used to model and treat human disease. In this example, the patient has a neurodegenerative disorder. Patient-specific iPS cells — in this case derived by ectopic co-expression of transcription factors in cells isolated from a skin biopsy — can be used in one of two pathways. In cases in which the disease-causing mutation is known (for example, familial Parkinson’s disease), gene targeting could be used to repair the DNA sequence (right). The gene-corrected patient-specific iPS cells would then undergo directed differentiation into the affected neuronal subtype (for example, midbrain dopaminergic neurons) and be transplanted into the patient’s brain (to engraft the nigrostriatal axis). Alternatively, directed differentiation of the patient-specific iPS cells into the affected neuronal subtype (left) will allow the patient’s disease to be modelled in vitro, and potential drugs can be screened, aiding in the discovery of novel drugs. From Robinton and Daley (2012).

 


Instructor: Dr. Klaus O. Kalthoff
Office: BIO 314
Phone / Email: (512) 471-1412 / kkalthoff@austin.utexas.edu
Prerequisite: Credit for or concurrent enrollment in BIO 346
Topic:

Pluripotent Stem Cells for Studying Cell Differentiation, Modeling Human Disease, and Screening Drugs (see summary at end of this web site). As a "warm-up", I recommend the review article by Robinton and Daley (2012).

Time, Place:

Class meets on Wednesdays, 2-4 pm, in WEL 3.402
First class meeting is on 19 March (after spring break, see Syllabus below)
Last class meeting is on 23 April (guest lecture)

Guest Lecturer:

Dr. Jonghwan Kim, Assistant Professor in the Department of Molecular Biosciences, , College of Natural Sciences, UT Austin.

Tentative Syllabus
19 March Instructor's outline (Kalthoff (2014a), Kalthoff (2014b)) and discussion of Takahashi and Yamanaka ((2013)
26 March Discussion of Hanna et al. (2007) and Itzhaki et al. (2011)
02 April Discussion Hayashi K. et al. (2011) and Hayashi K. et al. (2012)
09 April Discussion of Hanna et al. (2009) and Rais et al. (2013)
16 April Discussion of Kim et al. (2008) and Hu et al. (2009)
23 April Guest lecture by Dr. Kim on "Transcription factor-mediated cellular reprogramming"

 
Course Policies:

Note that BIO 137 is no longer required for graduation in Human Biology. You should enroll in this seminar only if you are interested in the subject matter.

Grading will be pass/fail, based on attendance and participation. I will take notes on both. You should plan to attend class regularly, especially the guest lecture, but you may miss one class meeting, no questions asked.

The main purpose of each class meeting, except for the guest lecture, will be the discussion of the assigned readings, which may be review articles or original research papers. To access the readings, click on the links in the syllabus; feel free to print the readings for your personal use. You will be expected to participate in these discussions, which of course requires that you are familiar with the readings for the day. You may also bring up your own questions on the general topic; this is your seminar.


 

Summary of Seminar Topic

THE USE OF PLURIPOTENT STEM CELLS FOR STUDYING CELL DIFFERENTIATION, MODELLING HUMAN DISEASE, AND SCREENING DRUGS

Cell differentiation, such as the formation of neurons or blood cells, has long been a central issue of developmental biologists.  For their pioneering in this field, Sir John Gurdon and Shinya Yamanaka received the Nobel Prize in Physiology or Medicine in 2012.  Gurdon cloned frogs by transferring nuclei from gut epithelium into oocytes, thus showing that cell differentiation can be reversed.  More than forty years later, Yamanaka transformed mouse epidermal cells by adding the genes for four transcription factors.  Some of the transformed cells became pluripotent, that is, they developed into any type of differentiated cell if cultured in appropriate media.   These versatile cells were called induced pluripotent stem cells (iPSC) because they resembled embryonic stem cells (ESC), which had been generated earlier from embryonic cells.  Both iPSC and ESC are pluripotent and divide indefinitely.

The discovery of ESC and iPSC has triggered a flurry of research.  Recent discoveries are shedding new light on the roles of transcription factors and histone modifiers in controlling the patterns of gene expression in development.  Also, iPSC and ESC are of great interest for pharmacy and medicine.  Cell cultures from biopsies of human patients are already being used to test drugs for curative effects and toxicity in patients with different genetic backgrounds and disease histories.

In the future, it may be possible to use iPSC or ESC for cell replacement therapies.  For instance, a patient who survived a heart attack could be saved by injecting the damaged portion of the heart with cardiomyoblasts raised along the right steps from an iPSC or ESC culture.  Preliminary results with animals and human patients indicate that these procedures can work.  To translate them into regular clinical practice, many challenges still need to be overcome.

This seminar will explore some of the current thoughts and experiments on ESC and iPSC.  After an introduction by the instructor, students will discuss assigned review articles and original research papers.  The seminar will be capped off with a guest lecture by Dr. Jonghwan Kim, Assistant Professor in the Department of Molecular Biosciences at UT Austin.  Dr. Kim and his coworkers are actively researching regulatory networks controlling the “stemness” of ESC and iPSC.

Last updated 21 February 2014