Person:
Fahmy, Sarah

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Fahmy

First Name

Sarah

Name

Fahmy, Sarah

Filters

20171

Settings

Author's Publications: search.filters.isAuthorOfPublication.3cb6e3db-6952-4192-a5bf-58321b49072a

Search Results

Now showing 1 - 1 of 1
  • No Thumbnail Available
    Publication
    Using Induced Pluripotent Stem Cells and Cardiomyocytes to Model the Splicing Defect in the LMNA Gene That Causes Hutchinson-Gilford Progeria
    (2017-04-07) Fahmy, Sarah; Morris, James; Daheron, Laurence; Cowan, Chad
    Hutchinson-Gilford Progeria syndrome (HGPS) is an extremely rare, fatal, autosomal dominant disease affecting roughly one in 18 million children (Ullrich et al.2015). It is caused by a single base pair change in position 1824 resulting in a silent mutation (GGC > GGT) that causes a splicing defect in the LMNA gene. This resulting protein has a 50 amino acid deletion which is called progerin (Eriksson et al. 2003). Progeria is characterized by severe premature aging particularly affecting the skeletal-muscular system, the renal system, and the cardiovascular system. Patients with Hutchinson Gilford Progeria typically live only an average of 14.6 years of age, dying from a heart attack or stroke resulting from hypertension and atherosclerosis (Ullrich et al. 2015). The CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats) and associated Cas proteins originally found in Streptococcus pyogenes have been transformed into a revolutionary technology used in genome editing with long term hopes of therapeutic applications (Sander et al. 2014, Mali et al. 2015). Reprogramming somatic cells in to induced pluripotent stem cells is also an important tool in disease modeling (Yamanaka 2009). This research aims to create a stem cell model of the Hutchinson-Gilford Progeria LMNA mutation with CRISPR Cas9 genome editing technology and iPS reprogramming, and to observe the phenotypes associated with the G608G mutation in differentiated cardiac cells. This type of research allows for a better understanding of the pathology of the disease and provides insight as to which cell types are most affected. The goals of this research were three fold. First, to use CRISPR Cas9 tools and iPSC reprogramming to create an iPS line with the G608G in the LMNA gene. The second to differentiate the HGPS iPS cells generated from the first experiments into cardiomyocytes, and finally to evaluate the G608G phenotypes of cardiomyocytes and measure levels of metabolic markers indicative of hypertension caused by the G608G mutation, and the levels of progerin and LMNA expressed. In the future, these studies may be applied to research alternative stem cell therapies for humans with the progeria disease and in addition may provide greater insight to the pathology of atherosclerosis and the process of aging.