Patricia A D'Amore, Ph.D., MBA

Harvard Medical School

Charles L. Schepens Professor of Ophthalmology
Professor of Pathology
Co-Director, AMD Center of ExcellenceVice Chair for Basic Research and Translational Research

Mass Eye and Ear 

Director, Howe Laboratory
Associate Chief for Ophthalmology Basic and Translational Research
Mass General Hospital Executive Committee on Research, Ophthalmology Representative

Schepens Eye Research Institute of Massachusetts Eye and Ear

Director of Research
Ankeny Scholar in Molecular Biology of the Retina
Senior Scientist

Research Summary

Center/Research Area Affiliations

Biography

At the forefront of angiogenesis research for more than three decades, Patricia D’Amore investigates the mechanisms of vascular growth and development. She is particularly interested in the role of polypeptide growth factors, such as VEGF and TGF-ß, and in investigating the contribution of cell-cell interactions in the cells of the vasculature.

Dr. D’Amore’s foremost transformative contributions include the identification of VEGF as the elusive “Factor X” that causes pathological blood vessel growth in blinding neovascular eye diseases. She also developed a widely used mouse model of oxygen-induced retinopathy that served as the cornerstone of many basic scientific and preclinical studies of vascular development and disease. Her laboratory’s description of the genomic organization and functional characterization of the mouse gene that encodes VEGF potentiated major advances in the understanding of the molecular and genetic mechanisms that underlie both developmental and pathological VEGF expression. Collectively, these studies helped form the scientific foundations of vascular-targeting therapies that are currently used to treat various cancers and intraocular vascular diseases, such as AMD and diabetic retinopathy. In recognition of this groundbreaking work, Dr. D’Amore was one of seven co-laureates of the 2014 Antonió Champalimaud Vision Award.

More recently, Dr. D’Amore’s studies have uncovered important physiological roles of vascular growth factors—yielding crucial insight into the safe use of antiangiogenic therapies. Ongoing investigations are elucidating the molecular regulation of inflammation at the cellular level, the role of the endothelial glycocalyx in the regulation of angiogenesis, and the contribution of inflammation to the pathogenesis of AMD.

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

Education

Ph.D., Boston University (1977)
M.B.A., Northeastern University (1987)
Program on Negotiation, Harvard Law School (2011)

Postgraduate Training

Johns Hopkins Wilmer Eye Institute, Department of Ophthalmology, (1978-1979)
Johns Hopkins University School of Medicine, Department of Physiological Chemistry (1978-1981)

Honors

2016: William Silen Lifetime Achievement in Mentoring Award, Harvard Medical School
2015: Proctor Medal, Association for Research and Vision Ophthalmology
2014: Laureate, António Champalimaud Vision Award
2014: Endre A. Balazs Prize, International Society for Eye Research
2013: American Medical Association Women Physicians Sector Mentorship Award
2013: Everett Mendelsohn Excellence in Mentoring Award, Harvard University
2012: 10th Annual Marc J. Mass Memorial Lecture, Dept. Molecular & Cellular Pathology, University of North Carolina, Chapel Hill, NC
2012: Rous-Whipple Award, American Society of Investigative Pathology
2011: Third Annual Judah Folkman, M.D. Lectureship, Longwood Area Vascular Biology Seminar Series, Harvard Medical School
2010: 5th Annual Jeffrey M. Isner, M.D. Endowed Memorial Lectureship
2009: Gold Fellow, Association for Research in Vision and Ophthalmology
2006: A. Clifford Barger Excellence in Mentoring Award, Harvard Medical School
2006: Senior Scientific Investigator Award, Research to Prevent Blindness
2006: Inaugural David Shepro Lecture, Boston University
2005: Excellence Award, The Schepens Eye Research Institute of Mass. Eye and Ear
2004: Elected Member of The Academy at Harvard Medical School
1998-2003: Jules and Doris Stein Research to Prevent Blindness Professorship
1994: Alcon Research Institute Award
1993: Cogan Award, Association for Research in Vision and Ophthalmology
1986-1991: American Heart Association Established Investigator Award
1979: Meyers Honor Award for Research in Ophthalmology
1977: Lamport Award, The Microcirculatory Society
1972: Alvin T. Fuller Fellow, American Cancer Society

Her Story

Dr. D’Amore earned her PhD in Biology from Boston University in 1977. She was a postdoctoral fellow in Biological Chemistry and Ophthalmology at Johns Hopkins Medical School and then became an Assistant Professor of Ophthalmology. In 1981, she moved to Boston Children’s Hospital as Assistant Professor and is currently a Research Associate in Surgery. In 1998, she became Charles L. Schepens Professor of Ophthalmology and Professor of Pathology at Harvard Medical School and a Senior Scientist at the Schepens Eye Research Institute of Mass. Eye and Ear.

She is currently the Director of Research at Schepens Eye Research Institute, the Director of the Howe Laboratory at Mass. Eye and Ear, and the Vice Chair of Basic and Translational Research for the Department of Ophthalmology. Her research focuses on vascular growth and development, with an emphasis on blood-vessel growth in the retina. She believes that in order to decipher how disease processes occur, you must first have a thorough understanding of the normal processes. Work conducted in her laboratory, and in collaboration with investigators at Mass Eye and Ear, formed the basis for the current use of anti-angiogenic therapies for diabetic retinopathy.

Q & A with Dr. D’Amore

You study the vasculature. Can you describe it?

The vasculature can be compared to a plumbing system, with the heart as the major pump and the blood vessels as the pipes that supply all parts of the body. The architecture of blood vessels is like a tree, with the central trunk called the aorta, and the smallest branches called capillaries. It is at the capillary level that oxygen and nutrients diffuse out of the blood to nourish the tissues.

The term angiogenesis is in the news a lot. What does angiogenesis mean?

Angiogenesis comes from the terms “angio,” meaning blood, and “genesis” meaning birth. So angiogenesis is the growth of new blood vessels, specifically the smallest blood vessels (capillaries).

Why is there so much interest in angiogenesis?

Angiogenesis has become a topic of interest because of its central role in tumor growth. All tissues, including tumors, require a vascular supply to deliver oxygen and nutrients, and to remove CO2 and toxins. In the early 1970s, Judah Folkman at Children’s Hospital in Boston hypothesized that tumor growth could be prevented by blocking the growth of blood vessels into tumors. More importantly, most blood vessels in the adult are not growing, so it should be possible to develop therapies that target only the blood vessels growing into the tumors. With this, the idea of anti-angiogenic therapy was born.

On the other hand, there are diseases that are characterized by insufficient blood flow. Coronary artery disease—in which the vessels that nourish the heart are blocked—is a very common example. In this case, the goal would be to stimulate the growth of new blood vessels that could circumvent the blocked arteries. Therapies aimed at growing new blood vessels are called pro-angiogenic.

How does anti-angiogenic therapy differ from the standard tumor treatments?

Conventional anti-cancer treatment has generally used chemotherapy. This type of treatment uses relatively non-specific agents that target growing cells. Though tumors cells would most certainly be killed by this treatment, it also destroys other dividing cells such as hair follicles (which is why patients lose their hair), the cells that line the stomach (which is the cause of the nausea), and the blood-forming cells of the bone marrow (which is why people can become anemic, or have reduced numbers of white cells). In contrast, the anti-angiogenic therapies should target only the growing blood vessels, and therefore, should have significantly fewer side effects.

Another very important difference between conventional chemotherapy and anti-angiogenic therapy is that patients often develop “resistance” to specific chemotherapies. Resistance develops when a subset of tumor cells acquires the ability to continue to grow in the presence of the chemotherapeutic agent. When this happens the tumor stops responding to the therapy and continues to grow; that is, the tumor becomes “resistant.” Different chemotherapies can be used, but eventually the tumor develops a resistance to each one and the physician runs out of treatment options. This resistance is avoided by targeting the blood vessels instead of the tumor cells.

What does angiogenesis have to do with eye disease?

New blood-vessel growth is a complication of a number of common eye diseases, including very common pathologies, such as diabetic retinopathy and the wet form of macular degeneration. In both of these cases, new blood vessels grow in places where they normally should not. Furthermore, these new blood vessels are very leaky, and as a result, fluid can accumulate and disrupt vision.

Do tumor angiogenesis and eye angiogenesis have anything in common?

They have quite a bit in common. Perhaps not surprisingly, nature is very economical and uses the same molecules and mechanisms in many settings. A protein called vascular endothelial growth factor (VEGF) has been shown to be involved in both tumor angiogenesis and the angiogenesis associated with diabetic retinopathy and macular degeneration.

Are there any anti-angiogenic therapies available now?

The first anti-angiogenic therapy for cancer, called Avastin (made by Genentech), was approved for the treatment of colorectal cancer (in combination with chemotherapy) by the FDA. This drug is an antibody that can bind to VEGF and thereby block its action. The clinical trials that preceded its approval showed that, when used in combination with chemotherapy, it led to a four-month increase in survival when compared to chemotherapy alone. Since that time, a number of trials have been conducted to assess its effectiveness against other kinds of cancer.

Encouraged by the promising results against cancer, and knowing that VEGF had been shown to play a role in angiogenesis in the eye, ophthalmologists began to treat their patients with wet macular degeneration with Avastin—first intravenously and later by injection into the eye. Today, several anti-angiogenic therapies, including Lucentis and Eylea, have been FDA-approved for neovascular eye diseases.

You mentioned pro-angiogenesis. Is there any on-going work to develop pro-angiogenic therapies?

Investigators are developing methods to deliver the angiogenic factor VEGF to tissues that need new blood vessels. This is being done for heart disease, as well as for conditions where patients have insufficient blood flow to their legs (also called peripheral vascular disease).

Projects

Research Interests

  • Mechanisms of vascular growth and development
  • Angiogenesis
  • VEGFR2
  • VEGF
  • Endomucin
  • Age-related macular degeneration
  • Inflammasomes

Endomucin as a Novel regulator of Angiogenesis

The studies aim to determine the contribution of endomucin, an endothelial-specific cell surface proteoglycan, to pathologic angiogenesis and to understanding the mechanism by which endomucin regulates VEGFR2 signaling. Clinical application: Novel target for blocking pathologic neovascularization

Endomucin as a Regulator of Vascular Inflammation

Cell surface endomucin normally blocks endothelial cell-leukocyte interactions. Under inflammatory conditions, endomucin is shed, facilitating these interactions. Dr. D’Amore is investigating the mechanisms by which endomucin blocks leukocyte adhesion as well the molecular basis of its shedding from the cell surface. Clinical application: Suppression of ocular inflammation

Repurposing Troglitazone to Protect Retinal Pigment Epithelium

Dr. D’Amore, in collaboration with Dr. Eric Ng, have demonstrated that troglitazone can protect RPE from damage/death due to oxidized LDL. They are investigating the mechanisms of this protection and developing novel analogs. Clinical application: Prevention or attenuation of dry AMD

Lipid Handling by RPE: Effects of Aging and MicroRNAs

Dr. D’Amore’s group is examining the effect of aging on the expression of genes central to the normal handling of lipids by RPE, including ABCA1, SRB1 and CD36, to name a few. They are also investigating the regulation of these genes by specific miRNAs. Clinical application: Pathogenesis of AMD

Molecular Bases of the Eye Disease

The goal of this project is to train the next generation of scientists who will address the problems of eye disease by identifying new means of diagnosis, prevention and treatment.

Patents

For a complete list of Dr. D’Amore’s patents, download her CV [PDF].

Bioerodible articles useful as implants and prostheses having predictable degradation rates
US Patent No. 4,886,870; European Patent No. 86,106,813.8

Oligosaccharide-containing inhibitors of endothelial cell growth and angiogenesis
USN 07/342065. Application No. CA 2053883

Endomucin as an anti-inflammatory agent
US Patent No. 20,170,095,529, 2017

Publications

H-index

85 (Google Scholar, as of August 2017)

Selected Publications

Dr. D’Amore has published more than 150 peer-reviewed articles and 4 books. Below is a list of selected publications. View her publications on PubMed, Google Scholar, or ORCID.

  1. Zahr A, Alcaide P, Yang J, Jones A, Gregory M, dela Paz NG, Patel-Hett S, Nevers T, Luscinskas FW, Saint-Geniez, M, Ksander B, *D’Amore, PA,  *Argueso P (co-corresponding authors). Endomucin prevents leukocyte–endothelial cell adhesion and has a critical role under resting and inflammatory conditions. Nat Commun.2016 Feb 2;7:10363
  2. Gnanaguru G, Choi AR, Amarnani D, D'Amore PA. Oxidized lipoprotein uptake through the CD36 receptor activates the NLRP3 inflammasome in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2016 Sep 1;57(11):4704-12.
  3. Tseng WA, Thein T, Kinnunen K, Lashkari K, Gregory MS, D’Amore PA, Ksander BR. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013 Jan 7; 54:110-120.
  4. Saint-Geniez M, Kurihara T, Sekiyama E, Maldonado AE, D’Amore PA. An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris. Proc Natl Acad Sci. USA. 2009 Nov 3; 106:18751-18756. Epub 2009 Oct 19.
  5. Ng YS, Rohan R, Sunday ME, Demello DE, D’Amore PA. Differential expression of VEGF isoforms in mouse during development and in the adult. Dev Dyn. 2001 Feb; 220:112-121.

Laboratory

Current Members of Dr. Patricia D’Amore’s Laboratory

Administrative Coordinator
Erin Porter

Laboratory Manager
Kahira Saez-Torres

Postdoctoral Fellows
Gopalan Gnanaguru, PhD
Michelle LeBlanc, PhD

Alumni

More than 60 trainees have worked in Dr. D’Amore’s laboratory. To view the complete list of alumni, download her CV [PDF].