Subha Karumuthil Melethil

Subha Karumuthil Melethil, PhD


Research Associate

 

 

 

 


Contact Info

UNC Gene Therapy Center
CB# 7352
Chapel Hill, NC 27599

Office: 5111 Thurston Bowles
Phone:  919-962-2566
Fax: 
CV | Email

Research Interests

 My research in the Gray lab focuses on designing gene therapy approaches for global gene transfer in the CNS for treating Lysosomal Storage Diseases, specifically, Krabbe and Tay-Sach’s diseases.

Krabbe disease or Globoid Leukodystrophy is an autosomal recessive neurological disorder caused by mutations in the enzyme GALC. The main pathology is associated with the accumulation of psychosine and galactosylceramide, the substrates for GALC, in the nervous tissue. The complete loss of GALC function is fatal by 2-3 years old.

Tay-Sach’s disease is also an autosomal recessive neurodegenerative disease caused by mutations in the alpha subunit of the enzyme β-hexosaminidase, resulting in the deficiency of isoenzyme β-hexosaminidase A (HexA). This leads to excessive accumulation of GM2 ganglioside in the neuronal tissue.

My research work involves delivering the correct gene by AAV mediated gene transfer in models for these diseases. I aim to find out 1) the best-suited AAV serotype, 2) the therapeutic vector dose, 3) the vector delivery route and 4) the stage /age at which the gene is delivered, to extend the survival/life span of the affected animal model.

Additionally, I am interested in investigating the host immune responses to the delivered therapeutic gene. Given the immune system of the recipient might not tolerate a delivered foreign gene, I plan to explore different approaches by combining immune modulation techniques along with the vector delivery to develop an effective gene therapy strategy. 

Publications

 Subha Karumuthil-Melethil, Nicolas Perez, Mohammad Hanief Sofi, Radhika Gudi, and Chenthamarakshan Vasu. TLR2 and dectin 1 associated innate immune response modulates pancreatic beta cell antigen specific T cell response and prevents Type 1 diabetes. (Manuscript under review in Diabetes)

Subha Karumuthil-Melethil, Nicolas Perez, Roubing Li, and Chenthamarakshan Vasu. Fungal β-glucan, a Dectin-1 ligand, promotes protection from Type 1 Diabetes by inducing regulatory innate immune response. (Under review in J.Immunol.)

 M. Hanief. Sofi, Radhika R. Gudi, Subha Karumuthil-Melethil, Nicolas Perez, Benjamin M. Johnson, and Chenthamarakshan Vasu. (2014). pH of drinking water influences the composition of gut microbiome and type 1 diabetes incidence. Diabetes. 63(2):632-644.