Magali Saint-Geniez, Ph.D.

Harvard Medical School

Assistant Professor of Ophthalmology

Schepens Eye Research Institute of Massachusetts Eye and Ear

Assistant Scientist

Research Summary

Center/Research Area Affiliations

Biography

Dr. Saint-Geniez joined the Schepens Eye Research Institute of Mass. Eye and Ear in 2002 to complete her postdoctoral training in the laboratory of Dr. Patricia D’Amore. During her fellowship, she characterized the role of VEGF in ocular development and the maintenance of retinal homeostasis. Her current research program focuses on the characterization of novel molecular pathways involved in retinal degenerative pathologies such as Age-related Macular Degeneration, Retinal Detachment, and Proliferative Vitreoretinopathy. With support from the National Institutes of Health, the Brightfocus Foundation, the Lions Foundation of Massachusetts, the Grimshaw-Gudewicz Charitable Foundation, and Research to Prevent Blindness, she is investigating the underlying pathogenic roles of metabolic dysfunction and oxidative damage in photoreceptors and retinal pigment epithelium, as well as the therapeutic benefits of novel metabolic regulators using multidisciplinary approaches, including mouse model generation and molecular and metabolic biology. In 2015, Dr. Saint-Geniez, received the Cotran Early Career Investigator Award 2016 (ASIP) for her contribution to ocular research. During her academic career from fellow to independent investigator, Dr. Saint-Geniez has been committed to the education and mentoring of graduate students and post-doctoral fellows. She received the 2008 Schepens Fellow Group Leadership Award in Teaching and the 2014 Harvard Medical School Excellence in Mentoring Award (Young Mentor).

Download her CV or biosketch[PDF] for more information.

Education

M.S., Biology and Animal Physiology, University of Toulouse III (France) (1997)
Ph.D., Vascular Biology, University of Toulouse III (2002)

Postgraduate Training

Postdoctoral Fellowship, Schepens Eye Research Institute of Mass Eye and Ear (2002-2008)

Honors

2017: Alcon Research Institute Young Investigator Award
2015: Research to Prevent Blindness Dolly Green Special Scholar Award, New York, NY
2015: Cotran Early Career Investigator Award 2016, American Society for Investigative Pathology, Bethesda, MD
2014: Excellence in Mentoring Award, Young Mentor, Harvard Medical School
2010: Harvard Catalyst Award
2009: National Institutes of Health Director’s New Innovator Award
2008: Schepens Fellow Group Leadership Award: Teaching
2004: Best Poster Presentation, Department of Ophthalmology Retreat, Harvard Medical School, Boston, MA
2004: Schepens Eye Research Institute Postdoctoral Training Grant, “Role of RPE-derived VEGF in choroids development and stability”, Boston, MA
2001: Association for Cancer Research (ARC): Training Grant
1999: Fouassier Eye Research Award from the Fondation de France: Research
1998: French Association of Amblyopia (AFAU): Training Grant

Her Story

Early Research

Dr. Saint-Geniez is a research scientist specializing in ophthalmology. She conducted her graduate studies at the University of Toulouse III, France, and was awarded a competitive Training Grant from the French Associate and Amblyopia (AFAU). Her thesis project focused on the determination of the functions of a new G protein-coupled receptor, msr/apj, and its ligand, Apelin, during physiological and pathological angiogenesis.

In 2002, Dr. Saint-Geniez joined the Schepens Eye Research Institute of Mass. Eye and Ear to begin a postdoctoral fellowship in Dr. Patricia D’Amore's laboratory. Her research focused on the role of VEGF in ocular development and retina function and was funded by a competitive fellowship grant from the Schepens Eye Research Institute of Mass. Eye and Ear (2003-2004).

She demonstrated that VEGF was expressed by various cells during ocular organogenesis and identified a new autocrine VEGF pathway involved in lens fiber differentiation (IOVS 2009).

She also determined that VEGF is a survival factor for adult choroidal vessels (IOVS 2006) and showed that endogenous VEGF is required for the maintenance of the visual function. This work was published in Plos One (Nov 3, 2008) and featured in the November 2008 issue of Harvard Medical School Focus journal.

She used transgenic models to determine the function of RPE-derived VEGF in the maintenance of choroidal vessels and revealed that alteration of VEGF signaling in adult RPE leads to age-dependent anomalies of the back of the eye similar to geographic age-related macular degeneration (or dry AMD) confirming the hypothesis that endogenous VEGF is required for a healthy RPE-choroid complex (PNAS 2009). This work was featured in the February 2010 issue of the EyeNet Magazine, which is published by the American Academy of Ophthalmology.

Translational Research

As an independent investigator, Dr. Saint-Geniez is expanding her scientific interest to new translational research. Notably, she received the NIH Director’s New Innovator Award for the development of new porous polymeric scaffolds for ocular tissue bioengineering. For this project she combined biomaterial engineering and stem cells technology to design new methodology for the effective transplantation of RPE for the treatment of AMD (J Mater Sci Mater Med 2013) and characterized the interdependent relationship between choroidal endothelial cells and RPE (J Cell Mol Med 2017).

Based on these findings, she is now developing a novel computational method for estimating local oxygen concentration in the retina of AMD patients and predicting disease progression.

In addition, Dr. Saint-Geniez is examining the contribution of metabolic dysfunction and oxidative damage to common retinal pathologies. To this aim, she is determining the metabolic processes controlling retinal cells homeostasis and demonstrated that PGC-1a—a transcriptional coactivator that plays a central role in the regulation of cellular metabolism—regulates VEGFA in the retina and is required for normal vessel development and for pathologic neovascularization (AJP 2013). Furthermore she identified PGC-1α as a critical regulator of RPE cells’ oxidative metabolism with potent antioxidant activity (IOVS 2016).

She is now characterizing further the molecular mechanisms controlling RPE and photoreceptors metabolic activity in normal and pathological conditions with the goal to develop innovative therapeutic strategies

Projects

PGC-1 beta and Choroidal Neovascularization

This project aims to characterize the contribution of PGC-1β induction in RPE to neovascular AMD and to identify therapeutic methods for targeting pathway as therapy for advanced AMD.

Role of PGC-1 alpha in RPE Function and Oxidative Stress: Implications for AMD

This project aims to characterize the functions of PGC-1 alpha in the metabolic and degenerative processes of the retinal pigmented epithelium.

Roles of Metabolic Dysfunction and Sex Hormones in Retinal Detachment

This study aims to characterize the sex-specific metabolic alterations associated with retinal detachment (RD) and determine the function of steroid hormones in protecting photoreceptors from RD-mediated degeneration.

Patient-Specific Modeling of Oxygen Distribution for Predicting Retinal Degeneration

This project aims to develop a patient-specific computational model for predicting retinal degeneration due to hypoxia or hyperoxia in the retina.

Mechanobiology of RPE Cells

The goal of this study is to determine the impact of substrate stiffness on RPE biology and to characterize the role of substrate stiffening secondary to aging and/or pathology in the pathogenesis of age-dependent macular degeneration.

Current Research Funding

2018-2020

Targeting metabolism as a novel therapeutic approach for retinal degenerative diseases
Iraty Award
PI ($100,000)
This award supports on going projects aimed at evaluating the contribution of metabolic alterations to RPE/photoreceptor oxidative damage and degeneration during disease onset and progression.

2018-2020
Role of PGC-1beta in neovascular AMD
Brightfocus Foundation
PI ($160,000)
This project aims to characterize the contribution of PGC-1b to neovascular AMD and to identify therapeutic methods for targeting pathway as therapy for advanced AMD.

2016-2018
Unraveling the protective role of PGC1alpha on RPE dysfunction
The Grimshaw Foundation
PI ($145,000)
This proposal’s goal is to define the role of metabolic alterations to RPE oxidative stress and degeneration during dry AMD and explore the protective role of PGC-1a on RPE survival.



Publications

H-index

23 (Google Scholar, as of September 2018)

Selected Publications

Dr. Saint-Geniez has published more than 35 peer-reviewed articles, 3 reviews, 2 book chapters, and one commentary. Below is a list of selected publications. View her publications on PubMed or Google Scholar.

  1. Saint-Geniez, M., Maharaj, A. S., Walshe, T. E., Tucker, B. A., Sekiyama, E., Kurihara, T., Darland, D. C., Young, M. J., D’Amore, A. P. (2008) Endogenous VEGF Is Required for Visual Function: Evidence for a Survival Role on Müller Cells and Photoreceptors. Plos ONE. 2008;3(11): e3554.
  2. Saint-Geniez, M., Kurihara, T., Sekiyama, E., Maldonado, A.E., D'Amore, P.A. An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris. PNAS. 2009;106(44):18751-6.
  3. Saint-Geniez, M., Jiang, A., Abend, S., Liu, L., Sweigard, H., Connor, K.M. and Arany, Z. PGC-1α regulates normal and pathological angiogenesis in the retina. Am J Pathol. 2013 Jan;182(1):255-65
  4. Iacovelli, J., Rowe, G. C., Khadka, A., Diaz-Aguilar, D., Spencer, C., Arany, Z., Saint-Geniez, M. PGC-1α induces human RPE oxidative metabolism and antioxidant capacity. Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1038-51
  5. Spencer, C., Abend, S., McHugh, K.J., Saint-Geniez, M. Identification of a synergistic interaction between endothelial cells and retinal pigment epithelium. J Cell Mol Med. 2017 Apr 12.

Patents

Predicting Retinal Degeneration Based on Three-Dimensional Modeling of Oxygen Concentration
Saint-Geniez M, McHugh K, Leo K, inventors. PCT/US2014/035181. 2013 April 24.

Endomucin Inhibitor as an Anti-Angiogenic Agent
D’Amore PA, Saint-Geniez M, Park-Windhol C, inventors. PCT application. 2017 March 31.

Induction of PGC-1alpha for the Treatment of Degenerative Ocular Diseases
Saint-Geniez M, inventor. PCT application. 2018 March 5.


Laboratory

Current Members of Dr. Saint-Geniez Laboratory

Postdoctoral Fellow
Mariana Ap. B. Rosales

Alumni

More than 12 trainees have worked in Dr. Saint-Geniez’s laboratory. To view the complete list of alumni, download her CV [PDF].