Stanford’s NEI T32 Vision Research Training Program
Post-Doctoral Scholar Vision Research Training Grant
Stanford’s NEI T32 Vision Research Training Program is again requesting applications for post-doctoral fellowship. We will fund 3 scholars, each for 1 year, starting as early as Friday, July 1, 2022.
Application deadline: Friday, June 17, 2022 for July 1 start date, and then rolling applications thereafter, pending training slot availability.
Applicants should e-mail Daniel Morrison at daniel.morrison@stanford.edu with the attached completed application form and checklist, a CV (NIH biosketch is OK), and 2 letters of reference.
Eligibility:
Per NIH guidelines, candidates must have completed their PhD or MD or equivalent doctoral degree from an accredited domestic or foreign institution by the time they start, and must be a permanent resident or citizen of the United States. They must have a Stanford mentor engaged in vision research, and they must conduct research full-time within the mentor’s laboratory.
Research clinicians must devote full-time to their proposed research training and confine clinical duties to those activities that are part of the research training program.
Applications from underrepresented minorities are highly encouraged.
Goals:
This NEI T32 is designed to train future leaders in vision research who understand key clinical issues and causes of vision loss. The program includes,
1) Intensive clinical ophthalmologic exposure, especially targeting non-clinically trained investigators, to facilitate future bench-to-bedside applications of basic vision research.
2) Facilitation of the transition of MD and MD-PhD-trainees from clinical practice to rigorous vision research and fostering their successful application to the Career Development (K) Award, an important funding mechanism for physician-scientists.
3) The education and training of basic and clinical investigators from diverse backgrounds in molecular, cellular, synaptic, and systems level vision research to prepare them for academic careers in clinical and basic departments.
Training Program Overview:
Each Scholar will carry out his or her research under the direction of a mentor working on vision research and will spend the vast majority of time in the mentor’s laboratory. In addition, each trainee will have a research and a clinical mentor, who are in the Vision Training Program or Department of Ophthalmology, in order to expose the trainee to approaches in both basic science and translational disciplines. At the beginning of the program, these mentors will be assigned in consultation with the T32 trainee.
An awarded trainee position cannot be shared among multiple individuals. Trainees are expected to devote full time to training activities, which, in addition to their research, may include relevant course work, workshops, and scientific conferences, including the monthly Vision Colloquium, Ophthalmology Grand rounds, and the Bay Area Ophthalmology Course – an intensive, 4-week course offered every July.
The funding comes from the National Research Service Award (NRSA) institutional training grants (T32) from the National Eye Institute.
QUESTIONS? Please contact:
Daniel Morrison at daniel.morrison@stanford.edu
Year 5
Anna Bettina Toth, MD, PhD
Anna Bettina Toth, MD, PhD (Ophthalmology)*
· Mentor: Jeffrey Goldberg, MD, PhD
· Project Title: Regulation of astrocyte reactivity by soluble adenylyl cyclase in glaucoma
· Brief Summary: In glaucoma and other neurodegenerative diseases, astrocytes respond to injury through a remodeling process called reactive gliosis that can have a broad spectrum of neurotoxic and neuroprotective effects. We have previously implicated soluble adenylyl cyclase (sAC) signaling as critical for neuroprotective astrocyte proliferation after nerve crush injury. Here, I propose to determine the role of localized sAC and sAC-derived cAMP on astrocyte reactivity and RGC survival after glaucomatous injury.
Sahil Shah, MD, PhD
Sahil Shah, MD, PhD (Neurosurgery)*
· Mentor: Sui Wang, PhD
· Project Title: The role of cargo specificity of Kinesin-1 motor proteins in neuro-degeneration of the visual system
· Brief Summary: Protein transport deficits in retinal ganglion cells after glaucomatous injury have been shown to exacerbate neurodegeneration. Although the function of motor protein Kif5a is primarily affected, it is not known which cargo needed in the axon and axon terminal of retinal ganglion cells rely specifically on Kif5a transport, how Kif5a transport is regulated, and how alternative motors compensate for the loss of Kif5a. We aim to define the cargo specificity of the individual Kinesin-I superfamily members in retinal ganglion cells, identify the regulatory pathway underlying azonal translocation of Kinesin-I proteins, and restore homeostatic balance of effector molecules through viral therapy.
David Dennis, PhD
David Dennis, PhD (Ophthalmology & Medicinal Chemistry)
· Mentors: Vinit Mahajan, MD, PhD, and Mark Smith, PhD
· Project Title: Selective inhibitors of HTRA1 for the Understanding of and Treatment of AMD
· Brief Summary: A medicinal chemistry focused effort to explore the target protease HTRA1 and it’s role in Age-related Macular Degeneration (AMD). By developing inhibitors of HTRA1, conducting structure-activity relationship (SAR+ studies, and optimizing pharmacokinetic parameters for delivery to the eye, I aim to develop a small molecule therapeutic for the treatment of AMD.
Year 1:
Luciano Custo Greig
Mentor: Sui Wang
Title: Single cell molecular analysis of Müller glia diversity and responses to retinal injury
Summary: Recruitment of Müller glia for regeneration of retinal neurons following injury or degeneration has been an area of intense interest and promising advances in the field of retinal repair, yet little is known regarding the extent of diversity present within this broad cellular population. We propose using single cell RNAseq to profile Müller glia gene expression in order to identify transcriptional clusters corresponding to biologically meaningful subtypes or cellular states. We also plan to investigate the transcriptional response of individual Müller glia to retinal injury, so that we may discern any heterogeneity in these responses and define the temporal dynamics and relevant molecular pathways.
Gabriella Fernandes Cunha
Mentor: David Myung
Title: Secretome-inspired therapy to prevent corneal blindness
Summary: Human mesenchymal stem cells (MSCs) applied to the wounded eye have been shown to improve the rate of wound healing possibly due to the paracrine factors produce by these cells (the secretome). We hypothesized that synergistic effects between the secretome and hyaluronic acid that we have observed on corneal wound healing are related to modulation of the corneal crystalline ALDH3A1 and the transmembrane protein CD44. In this project we aim to understand the factors that preserve corneal transparency after alkaline burns and elucidate the molecular mechanisms in which secretome enhances cornea wound healing.
Hannah Webber
Mentor: Yang Hu
Title: Elucidating the Molecular Mechanism of Optineurin in Glaucomatous Neurodegeneration
Summary: Mutations of the optineurin gene including the most common mutant Optineurin-E50K, have been confirmed as causative in some familial normal tension glaucoma patients. By examining variants of optineurin specifically in retinal ganglion cells, the primary cells affected in normal tension glaucoma, we will determine whether a loss-of-function of OPTN or a gain-of-function of OPTN causes RGC degeneration. Our studies will determine the intrinsic role of optineurin in retinal ganglion cell degeneration and uncover the therapeutic potentials of targeting the optineurin pathway in normal tension glaucoma.
Year 2:
Tia Kowal
Mentor: Yang Sun
Title: The role of primary cilia for retinal ganglion cells.
Summary: Glaucoma is a blinding condition that affects nearly 2 million people in the United States, yet the mechanisms of glaucoma development remain poorly understood and the treatments are limited. Glaucoma is characterized by deterioration of retinal ganglion cells, which have a primary cilia, an antenna-like organelle that projects from the cell surface and acts like a hub for cellular signaling pathways. Since defects in primary cilia are known to cause diseases such as Lowe Syndrome that have conditions including glaucoma, this application proposes research to investigate the primary cilia as a novel target for glaucoma treatment and to determine its basic biological function for retinal ganglion cells.
Dylan Parsons
Mentor: Vinit Mahajan/Mark Smith
Title: Selective Inhibitors of CAPN5 for the Treatment of Inflammatory Eye Disease
Summary: Our overall goal is to treat patients suffering from neovascular inflammatory vitreoretinopathy (NIV) and prevent blindness. We intend to accomplish this through the development of an intraocular small molecule inhibitor of the calpain-5 (CAPN5) protease, which has been demonstrated to cause neovascular inflammatory vitreoretinopathy (NIV). Our approach is two-fold, including (A) the development of peptidomimetc inhibitors based on generic calpain inhibitors; and (B) the development of a cyclic peptidomimetic based on peptide substrates within a high affinity to CAPN5.
Mable Lam
Mentor: Bradley Zuchero
Title: Mapping the mechanisms of optic nerve myelination
Summary: Myelination of the optic nerve is crucial for transmitting signals from the eye to the brain. Strategies to remyelinate the optic nerve after injury or autoimmune disorders, such as optic neuritis, are lacking due to limited knowledge about the fundamental mechanisms that construct myelin sheaths. I propose to determine the mechanisms by which vesicular trafficking in oligodenodcytes coordinate the proper presentation of proteins and lipids to promote axon ensheathment and membrane wrapping during myelination.
Year 3:
Caitlin Logan
Mentor: David Myung
Title: Supramolecular Hyaluronic Acid Gel Vehicle for Limbal Stem Cell Delivery to the Wounded Cornea.
Summary: Currently, there is no suitable biomaterial FDA approved for use today that facilitates engraftment of a cultured limbal stem cells (LESCs) to the corneal surface and development of this carrier system would meet a major clinical need for better treatment modalities for corneal blindness as a result of limbal stem cell deficiency. LESC self-renewal and differentiation are strongly influenced by their mechanical environment and a biomaterial’s structure and mechanical properties can constrol LERSC adhesion and differentiation into terminal corneal epithelial cells. The goal of this proejct is to investigate supreamolecular, non-covalently crosslinked assemblies of hyaluronic acid as suitable matrices for limbalstem cells to successfully engraft and remodel corneal tissue.
Sam Cooler
Mentor: EJ Chichilnisky
Title: Finding rare cell types in the macaque and human retina using automated neuronal classification
Summary: Recent findings in our lab have revealed that our immense and unique trove of 512-electrode recordings from primate retina, and a few from human retina, contain information about 4-8 novel cell types that are poorly understood. I will design and implement an automated classification system to mine these data for information on the new cell types, and then to further characterize the properties of these cell types during future experiments. These results will expand our knowledge of the non-human primate and human retina, and will be used in the development of a high-fidelity retinal implant being developed in our lab for treating incurable blindness.
Aubrey Hargrave
Mentor: Alfredo Dubra/Heather Moss
Title: Novel foveal pit pathology in multiple sclerosis
Summary: Multiple sclerosis (MS) is characterized by inflammation and axonal degeneration, affecting retinal ganglion cells and their axons; however, these changes do not fully account for the visual function deficits reported by multi-focal electroretinogram. We have identified the presence of the novel microscopic structures in the foveal avascular zone (FAZ), and these features correlate with visual dysfunction in MS subjects. We seek to extend this observation and determine whether the foveal features are correlated with any further visual or systemic pathology.
Year 4:
Brian Soetikno
Mentor: Alfredo Dubra/Joyce Liao
Title: Developing visible optical coherence tomography (vis-OCT) technology to image inner plexiform layer alterations in patients with glaucoma
Summary: This project will enable high-resolution imaging of the inner plexiform layer sub-laminae in patients with glaucoma using visible light optical coherence tomography (vis-OCT). We will design and construct a human vis-OCT system with key improvements for human imaging. We plan to develop automatic retinal layer segmentation algorithms to robustly measure IPL sub-laminae boundaries.
Sean Wang
Mentor: Howard Chang
Title: Generating a single-cell multiomic atlas of the human eye to identify the cellular targets of noncoding variants associated with ocular disease
Summary: Genome-wide association studies (GWAS) have uncovered hundreds of genetic variants associated with eye disease, but most of these variants reside in noncoding regions of the genome, making it challenging to interpret their function. To elucidate the cellular targets of these noncoding variants, I plan to build a single-cell multiomic atlas of the human eye. This resource will enable greater interpretability of the growing number of ocular GWAS and serve as a powerful tool for the vision research community.
Tim Currier
Mentor: Thomas Clandinin
Title: Developmental specification of single-neuron visual physiology
Summary: In this project, I will investigate how development shapes the visual responses of single neurons in the Drosophila visual system. In parallel lines of study, I will correlate known developmental programs with visual response properties, and ask how variants of physiology-defining proteins are distributed through development. These studies will allow me to link the developmental trajectory of single cell types to the function of those same neurons.