Gray, David (2015 - 2016)

David is in the Immunity, Microbes & Molecular Pathogenesis home area of the MBIDP.  He joined the CMB training program in 2015.  His research mentor is Dr. Donald Kohn.  He received a B.S. degree in 2013 from UCLA.

Mentor: Dr. Donald Kohn

Research project:

Gene Correction of X-Linked Agammaglobulinemia Using Targeted Endonucleases

X-Linked Agammaglobulinemia (XLA) is one of the most common forms of primary immunodeficiency affecting about 1 in 200,000 people worldwide.  XLA is caused by mutations in Bruton’s tyrosine kinase (BTK), a protein required for B cell development and antibody production.  XLA patients are treated with immunoglobulin replacement therapy, but the treatment is expensive, imperfect, and requires monthly injections for life.  These limitations in current XLA treatment make it an attractive candidate for alternative approaches, such as gene therapy.

Our lab has successfully developed and applied gene therapy to treat Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) also known as Bubble Boy Disease.  The lab is also working towards new treatments for other hematopoietic disorders such as Sickle Cell Disease and X-Linked Hyper IgM Syndrome.

I am applying findings from our lab’s experience with hematopoietic diseases to develop a novel therapeutic treatment for XLA using targeted endonucleases known as TALENS (Transcription Activator-Like Effector Nucleases) and the CRISPR/Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats), to modify specific loci in a patient’s genome.  We will use these technologies to introduce corrective inserts or point mutations into hematopoietic stem cells from the patient’s bone marrow, which can then be given back to the patient without risk of graft versus host disease or transplant rejection.