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 various retinal degenerative diseases. With support from the National Institutes of Health, the Brightfocus Foundation, the Lions Foundation of Massachusetts, 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.

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. Currently, she is combining 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) In addition, Dr. Saint-Geniez is characterizing the role of new metabolic genes in pathological neovascularization of the retina. In collaboration with Dr. Arany (Beth Israel Deaconess Medical Center, Boston), she recently 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). Her laboratory is now investigating the role of PGC-1 isoforms in photoreceptor and RPE and their contribution to retinal diseases such as retinal degeneration and AMD.

Projects

PGC-1 Co-activators in Photoreceptor Development and Survival

This study aims to determine the function of the transcription factors PCG1s in photoreceptor development and retinal degenerative diseases.

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

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

Roles of Metabolism, Oxidative Stress and PGC-1 Isoforms in Retinal Detachment

This study aims to characterize the metabolic alterations associated with retinal detachment (RD) and determine the function of PGC-1s in RD-mediated retinal 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

2015-2017
Research to Prevent Blindness Scholar: Principal Investigator (PI)
Roles of metabolism, oxidative stress and PGC-1 isoforms in retinal detachment
$25,000

2016-2018 The Grimshaw Foundation: PI
Unraveling the protective rol fo PGC-1 alpha on RPE dysfunction
$145,000

2016-2017
Foundation for Ophthalmology Research and Education: PI
Novel gene therapy approach for the treatment of dry AMD
$25,000
2017-2018 Alcon Research Institute Young Investigator Award: PI
Targeting RPE metabolism in AMD
$50,000

Publications

H-index

23 (Google Scholar, as of August 2017)

Selected Publications

Dr. Saint-Geniez has published more than 30 peer-reviewed articles, 3 reviews, and 2 book chapters. 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.

Laboratory

Current Members of Dr. Saint-Geniez Laboratory

Postdoctoral Fellow
Mariana Ap. B. Rosales

Undergraduate Students
Quincy Charles
Sangeeta Satish

Alumni

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