Marcus Toral received his bachelor's degree in Zoology and Neuroscience from Miami University in 2013 and was accepted into the University of Iowa NIH Medical Scientist Training Program (MSTP). He is working to complete his dual MD and PhD degrees and is currently finishing his PhD dissertation work at Stanford University in the lab of Dr. Vinit Mahajan.
Marcus Toral's research is focused on investigating the biochemistry, genomics, and proteomics of blinding eye diseases. Marc aims to identify new molecular targets and pathways in the eye to develop new treatment options for patients suffering from blindness.
Current Role at Stanford
Graduate Research Assistant
Honors & Awards
Award for Best Talk, University of Iowa Graduate Program in Molecular Medicine (Sep 2017)
Award for Best Poster Presentation, University of Iowa Carver College of Medicine Health Sciences Research Week (Apr 2017)
Award for Best Presentation by Predoctoral Trainee, FASEB International Conference on Calpain Biology (Jul 2016)
Award for Research in Ophthalmology, Best Medical Student Presentation, University of Iowa Hospitals and Clinics Department of Ophthalmology (Sep 2014)
Education & Certifications
B.A., Miami University, Oxford, Oh, Zoology and Neuroscience (2013)
PhD thesis work in the Mahajan Lab, Stanford University
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. Uniquely, as the stages of ADNIV mimic more common retinal diseases--such as diabetic retinopathy, uveitis, and proliferative vitreoretinopathy--this work promises to be broadly applicable to the treatment of vision loss.
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.
Palo Alto, California
Structural modeling of a novel SLC38A8 mutation that causes foveal hypoplasia
Molecular Genetics & Genomic Medicine
2017; 5 (3): 202-209
Foveal hypoplasia (FH) in the absence of albinism, aniridia, microphthalmia, or achromatopsia is exceedingly rare, and the molecular basis for the disorder remains unknown. FH is characterized by the absence of both the retinal foveal pit and avascular zone, but with preserved retinal architecture. SLC38A8 encodes a sodium-coupled neutral amino acid transporter with a preference for glutamate as a substrate. SLC38A8 has been linked to FH. Here, we describe a novel mutation to SLC38A8 which causes FH, and report the novel use of OCT-angiography to improve the precision of FH diagnosis. More so, we used computational modeling to explore possible functional effects of known SLC38A8 mutations.Fundus autofluorescence, SD-OCT, and OCT-angiography were used to make the clinical diagnosis. Whole-exome sequencing led to the identification of a novel disease-causing variant in SLC38A8. Computational modeling approaches were used to visualize known SLC38A8 mutations, as well as to predict mutation effects on transporter structure and function.We identified a novel point mutation in SLC38A8 that causes FH. A conclusive diagnosis was made using OCT-angiography, which more clearly revealed retinal vasculature penetrating into the foveal region. Structural modeling of the channel showed the mutation was near previously published mutations, clustered on an extracellular loop. Our modeling also predicted that the mutation destabilizes the protein by altering the electrostatic potential within the channel pore.Our results demonstrate a novel use for OCT-angiography in confirming FH, and also uncover genotype-phenotype correlations of FH-linked SLC38A8 mutations.
View details for DOI 10.1002/mgg3.266
View details for PubMedCentralID PMC5441399
Personalized Proteomics in Proliferative Vitreoretinopathy Implicate Hematopoietic Cell Recruitment and mTOR as a Therapeutic Target
American Journal of Ophthalmology
To profile vitreous cytokine expression of proliferative vitreoretinopathy (PVR) patients DESIGN: Case-control study.Liquid biopsies were collected from two groups: control subjects (n=3) undergoing pars plana vitrectomy to remove an epiretinal membrane (ERM), and test subjects (n=7) with varying degrees of PVR. A high-throughput cytokine screen measured expression of 200 cytokines. Cytokine expression patterns were prospectively validated in separate cohorts of control patients and those with PVR-A, PVR-B, and PVR-C (n=10 for each group). Expression changes were evaluated by ANOVA (significant p-value <0.05), hierarchical cluster algorithm, and pathway analysis, to identify candidate pathways for prospective studies.In PVR vitreous, 29 cytokines were upregulated compared to controls. Early-PVR vitreous showed upregulation of T-cell markers, pro-fibrotic cytokines, and cytokines downstream of mTOR activation (IL-2, IL-6, and IL-13), whereas late PVR vitreous, cytokines driving monocyte responses and stem-cell recruitment (SDF-1) prevailed. Prospective validation confirmed the differential-expression of specific cytokines from PVR-A to C.Early PVR is characterized by activation of T-cells and mTOR signaling, whereas advanced-PVR is characterized by a chronic monocyte response. PVR might be treated by rational repositioning of existing drugs that target mTOR and IL-6. Our analysis demonstrates that successful therapeutic intervention will be highly dependent on the specific therapeutic target and the stage of PVR. This study provides insights into cytokines that will serve as biomarkers and therapeutic targets. These biomarkers will help design clinical trials that intervene at appropriate times.
View details for DOI 10.1016/j.ajo.2017.11.025
Dissection of Human Retina and RPE-Choroid for Proteomic Analysis
Journal of Visualized Experiments (JoVE)
View details for DOI 10.3791/56203
Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses
Investigative Ophthalmology & Visual Sciences
2016; 57 (6): 2509-21
View details for DOI 10.1167/iovs.15-18680
dHb9 expressing larval motor neurons persist through metamorphosis to innervate adult-specific muscle targets and function in Drosophila eclosion
2016; 76 (12): 1387-1416
View details for DOI 10.1002/dneu.22400