marcus-toral@uiowa.edu
Mentor: Vinit Mahajan, M.D./Ph.D.
Lab Room: 1257C CBRB
Lab Phone: 319-384-1700

Understanding and Developing New Molecular Therapies for Inherited Blinding Diseases

My work in the Mahajan Lab is focused on understanding and developing new treatments for inherited blinding diseases. Specifically, our work focuses on studying a particularly devastating form of inherited blindness called Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV). Named for its clinical descriptors, ADNIV progresses through distinct pathological stages as it progresses, blinding individuals it afflicts. To date, there is no cure for ADNIV. However, the Mahajan lab is working to develop new therapies for ADNIV and other inherited blinding diseases. Work in the Mahajan lab has led to the discovery that ADNIV is caused by mutations to the gene CAPN5, which encodes the regulatory protease Calpain-5. Interestingly, our data indicates that Calpain-5 becomes hyperactive in the photoreceptor cells of the retina, over-processing its protein targets and leading to cell death and inflammation.

My thesis work is focused on studying the proteins targeted by Calpain-5 in the retina, aiming to understand the significance of these pathways in photoreceptor health and disease, as well as to identify new therapeutic targets for blinding diseases. Additionally, I am involved in projects looking at Calpain-5 biology and biochemistry, development of new retina dissection techniques, and understanding the molecular basis for novel inherited eye diseases.



Cabral T*, Toral MA*, Velez G, DiCarlo JE, Gore AM, Mahajan M, Tsang SH, Bassuk AG, Mahajan VB. Dissection of human retina and RPE-Choroid for proteomic analysis. Journal of Visualized Experiments (JoVE). Accepted 2017, in preparation. *Indicates authors contributed equally.

Toral MA, Velez G, Boudreault K, Schaefer KA, Xu Y, Saffra N, Bassuk AG, Tsang SH, Mahajan VB. Structural modeling of a novel SLC38A8 mutation that causes foveal hypoplasia. Molecular Genetics & Genomic Medicine. 2017;5(3):202-209. PMCID: PMC5441399.

Schaefer K, Toral MA, Velez G, Cox A, Baker S, Borcherding N, Colgan D, Bondava V, Mashburn CB, Yu C, Geddes J, Tsang SH, Bassuk AG, Mahajan VB. Calpain-5 expression in the retina localizes to photoreceptor synapses. Invest Ophthalmol Vis Sci. 2016;57(6):2509-21. PMID: 27152965.

Banerjee S, Toral M, Siefer M, Conway D, Dorr M, Fernandes J. dHB9 expressing larval motor neurons persist through metamorphosis to innervate adult-specific muscle targets and function in Drosophila eclosion. Developmental Neurobiology. 2016;76(12):1387-1416. PMID: 27168166.

Roybal CN, Velez G, Toral MA, Tsang SH, Bassuk AG, Mahajan VB. Personalized Proteomics in Proliferative Vitreoretinopathy Implicate Hematopoietic Cell Recruitment and mTOR as a Therapeutic Target. Am J Ophthalmol. 2018 Feb;186:152-163. doi: 10.1016/j.ajo.2017.11.025. Epub 2017 Dec 13. PubMed PMID: 29246578; PubMed Central PMCID: PMC5805631.