We have been investigating the role of pro- and antiangiogenic factors for blood vessel formation - angiogenesis - during development and in pathological conditions. Using mouse genetics, we inactivated either proangiogenic factors or antiangiogenic factors in vivo and assessed the effects of such an induced imbalance between these factors. Tissue-specific inactivation of the major proangiogenic factor VEGF in epithelial tissues resulted in reduced blood vessel formation in adjacent tissues. For example, inactivation of VEGF expression specifically in the retinal pigment epithelium in the eye led to reduced formation of adjacent choroidal vessels, resulting in retinal degeneration.
In contrast, lack of the antiangiogenic endostatin increased induced angiogenesis in vivo. Using a laser-injury model for choroidal neovascularization, the most common cause of blindness in patients with age-related macular degeneration, we could demonstrate that mice lacking endostatin had a significantly increased angiogenic response to the laser injury, while endostatin administration rescued this phenotype.
Current experiments aim at determining the role of different cell populations in the control of angiogenesis during development and disease, and at understanding the molecular mechanisms that regulate blood vessel formation and growth. We use temporal cell-specific gene inactivation approaches in order to determine the cell-type specific mechanisms that are involved in the regulation of physiological angiogenesis, but also pathological angiogenesis, in particular tumor angiogenesis.
Extracellular matrix biology and epithelial-mesenchymal interactions in the skin
A large body of evidence shows that many epithelial functions are regulated through interactions with adjacent tissues. Epithelial-mesenchymal interactions are important for tissue homeostasis, but also for pathological conditions such as cancer. The basement membrane zone, separating epithelial or endothelial cells from adjacent tissues, has also many regulatory functions in addition to being a structural scaffold to which cells adhere. For example, the basement membrane component collagen XVIII is a structural component of basement membrane molecular networks, while its proteolytically derived fragment endostatin has complex additional functions (e.g. inhibition of endothelial cell migration and proliferation).
We are interested to identify molecular mechanisms that play important roles in the regulation of epithelial-mesenchymal interactions, particularly in the skin and in skin cancer.
Fully NIH (R01 grant) funded postdoc position immediately available at Massachusetts General Hospital/Harvard Medical School
Mechanisms of Pathological AngiogenesisCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital/Harvard Medical School, BostonLaboratory of Dr. Alexander G. Marneros.
Assistant Professor of Dermatology, Harvard Medical SchoolWe are using mouse models to investigate mechanisms of postnatal angiogenesis in several pathologic processes.
Conditional gene targeting strategies and in vivo analyses are used to precisely determine mechanisms of pathological blood vessel formation.
- Ph.D. with strong background in molecular biology; at least one first-author publication
- Experience in working with mice absolutely required
- Ability to work independently within a dynamic team
- Able to start position ASAP
Interested candidates should send the CV and references to Alexander G. Marneros, M.D., Ph.D.,
The MGH/Harvard Cutaneous Biology Research Center is a committed Equal Opportunity/Affirmative Action Employer. Minorities, women, handicapped and veterans are encouraged to apply.
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