Download Department of Biological Sciences, University of Mary Washington

Smith-Magenis Syndrome and the Retinoic Acid Induced 1 Gene
Undergraduate Research Projects in the Zies Laboratory
Department of Biological Sciences, University of Mary Washington, Fredericksburg, VA
Dr. Deborah Zies
Current
Position
Research
Position
RAI1 is a Transcription Factor
Associate Professor of Biological Sciences
at UMW since 2006
A
Post Doctoral Research Fellow
Mayo Clinic, Jacksonville, Florida
“ PPARg/TGFb in the Intestinal Epithelium”
Education Ph.D. in Biochemistry and Molecular Biology
University of Florida, Gainesville, Florida
“Characterization of the Rabbit HKa2 Gene”
M.S. in Biology
Tulane University, New Orleans Louisiana
“Characterization of Insertion element IS511”
Transcription factors are proteins that regulate the
expression of other genes.
B
RAI1 (B) has been shown to regulate the
transcription of several genes (C) that have functions
that are related to the symptoms of SMS (D).
C
Currently, there is nothing known about the factors
that regulate the expression of RAI1 (A).
D
B.A. in Biology
Rollins College, Winter Park, Florida
The two main goals of the Zies laboratory are:
1. To determine the mechanism by which RAI regulates other genes.
2. To determine the mechanism by which RAI1 is regulated.
Smith-Magenis Syndrome (SMS)
How Does RAI1 Regulate CLOCK?
Human Intellectual Disability Disorder that affects
approximately 1/ 25,000 births worlds wide.
One gene known to be regulated by RAI1 is CLOCK, a major component of our day/night
circadian rhythm. One type of evidence for this regulation came from the luciferase reporter
gene assay performed in the Zies Laboratory.
Symptoms include:
• Mild to moderate intellectual disabilities.
• Distinctive facial abnormalities
• including full cheeks
• prominent lower jaw
• square-shaped face (Pictured: d, e, f)
• Disrupted sleep patterns
• Behavioral Disorders including
• self-hugging,
• Skin picking (Pictured: g),
• impulsiveness.
• Short fingers and toes (Pictured: h, i)
The regulatory region of CLOCK was cloned into the luciferase reporter gene plasmid. As seen
in the figure below (first two bars), there was approximately 3.5 fold higher luciferase activity
when the CLOCK plasmid was transcribed in the presence of RAI1 (dotted line represents
activity in the absence of RAI1).
The CLOCK plasmid was then broken into smaller pieces and the new constructs were then
tested for luciferase activity when treated alone and also with RAI1. It was found that all
fragments contained the RAI1 regulatory region except for deletion 6(+).
Critical Region Is Deleted on Chromosome 17 in SMS Patients
An ongoing project of the Zies Laboratory is to identify the smallest sequence that contains
the RAI1 regulatory region. Identification of this sequence will help identify other genes that
are regulated by RAI1.
What Regulates RAI1 transcription?
• SMS Patients with deletions were divided into groups depending on their deletion type:
• A common deletion (pink)
• An atypical deletion (green)
• a small deletion (blue)
• a large deletion (maroon).
• Genes that were in the region in which all patients shared the deletion were sequenced in
non-deletion patients and all of those patients had a mutation in the RAI1 gene (red box).
While we have made significant progress in
understanding the mechanism by which RAI1 regulates
other genes, we know very little about what regulates
the transcription of RAI1.
We have purchased five DNA fosmids from the human
genome project (boxed sequences). An ongoing
project of the Zies laboratory is to isolate the
regulatory region for RAI1 from these DNA fosmids
and identify specific sequences involved in the
regulation of RAI1.
Past Lab Members
Christine Chapman
Tyler Andrew Cox
Christine Bax
Bachelor of Science: University of Mary Washington, May 2008
Master of Science: University of New Hampshire, December 2011
Current Position:
Research Technician, Tufts University
Bachelor of Science: University of Mary Washington, May 2009
Master of Science:
University of Miami, May 2012
Current position:
Science & Policy Specialist, Billfish Foundation
Bachelor of Science: University of Mary Washington, May 2011
Current position:
Associate Scientist
Pharmaceutical Product Development, Inc.
Rose Salzberg
Melissa Hadley
Bachelor of Science: University of Mary Washington, May 2009
Doctor of Pharmacy: Virginia Commonwealth University
Anticipated Graduation Date: May 2013
Bachelor of Science: University of Mary Washington, May 2010
Current position:
Graduate student, Eastern Virginia Medical School
Anticipated Date:
May 2013
Rabia Aman
Brent Colin Turner
Jonathan Hillyard
Bachelor of Science: University of Mary Washington, May 2009
Master of Science: Johns Hopkins School of Public Health, May 2012
Current Position:
Medical School Student, Medical College of Virginia
Bachelor of Science: University of Mary Washington, May 2010
Master of Science:
Drexel University College of Medicine, May 2012
Current Position:
Osteopathic Medical Student, VCOM
Karen Strat
Emily Griffith
Brittany Abbatiello
Andrew Buckner
Bachelor of Science: University of Mary Washington, May 2009
Current position:
Graduate student, University of Oklahoma
Anticipated Graduation Date: May 2015
Bachelor of Science: University of Mary Washington, May 2011
Current position:
Technical Intramural Research Award Trainee
National Institutes of Health
Bachelor of Science: University of Mary Washington, December 2012
Current position:
Lab Technician
University of Virginia
Bachelor of Science: University of Mary Washington, May 20 12
Current Position:
Applying to Medical School
Bachelor of Science: University of Mary Washington, May 2012
Current position:
Graduate Student, Virginia Tech