Massachusetts General Hospital

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.
Required profile:
- 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.,
Email:  amarneros@partners.org

The MGH/Harvard Cutaneous Biology Research Center is a committed Equal Opportunity/Affirmative Action Employer. Minorities, women, handicapped and
veterans are encouraged to apply.

Publications

• He L and Marneros AG.  Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar.  Am J.Pathol. 2013 Apr. 18 doi:pii S2002-9440(13)2011-3 10.1016/j.apath.2013.02.032
• Marneros AG, Beck AE, Turner EH, McMillin MJ, Edwards MJ, Field M, de Macena Sobreira NL, Perez AB, Fortes JA, Lampe AK, Giovannucci Uzielli ML, Gordon CT, Plessis G, Le Merrer M, Amiel J, Reichenberger E, Shively KM, Cerrato F, Labow BI, Tabor HK, Smith JD, Shendure J, Nickerson DA, Bamshad MJ; University of Washington Center for Mendelian Genomics. Mutations in KCTD1 cause scalp-ear-nipple syndrome. Am J Hum Genet. 2013 Apr 4;92
  (4):621-6. 
• Makinodan E, Marneros AG. Protein kinase A activation inhibits oncogenic Sonic hedgehog signalling and suppresses basal cell carcinoma of the skin. Exp Dermatol. 2012;21(11):847-52.
• Marneros AG. Tumor angiogenesis in melanoma. Hematol Oncol Clin North Am, 2009;23(3):431-46.
• Marneros AG, Bickers DR. Non-melanoma skin cancer. In: Therapies in Dermatology, Springer (in press).
• Marneros AG, Grossman ME, Silvers DN, Husain S, Nuovo GJ, MacGregor-Cortelli B, Neylon E, Patterson M, O'Connor OA, Zain JM. Pralatrexate-induced tumor cell apoptosis in the epidermis of a patient with HTLV-1 adult T-cell lymphoma/leukemia causing skin erosions. Blood, 2009;113(25):6338-41.
• Marneros AG, Blanco F, Husain S, Silvers DN, Grossman ME. Classification of cutaneous intravascular breast cancer metastases based on immunolabeling of blood and lymph vessels. J Am Acad Derm, 2009;60(4):633-8.
• Marneros AG, She H, Zambarakji H, Hashimoto H, Connolly E, Kim I, Gragoudas E, Miller JW, Olsen BR. Endogenous endostatin inhibits choroidal neovascularization. FASEB J, 2007, 21(14):3809-3818.
• Marneros AG, Fan J, Yokoyama Y, Gerber HP, Ferrara N, Crouch, RK, Olsen BR. VEGF expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function. Am J Pathol, 2005;167: 1349-1357.
• Marneros AG, Olsen BR. Physiological role of collagen XVIII and endostatin. FASEB J., 2005; 19(7): 716-728.
• Marneros AG, Keene DR, Hansen U, Fukai N, Moulton K, Goletz PL, Moiseyev G, Pawlyk BS, Halfter W, Dong S, Shibata M, Li T, Crouch RK, Bruckner P, Olsen BR. Collagen XVIII and endostatin are essential for vision and retinal pigment epithelial function. EMBO J., 2004;23(1):89-99.
• Marneros AG, Krieg T. Keloids – clinical diagnosis, pathogenesis and treatment options. J Dtsch Dermatol Ges. 2004 Nov;2(11):905-13.
• Marneros AG, Norris JEC, Watanabe S, Reichenberger E, Olsen BR. Genome wide screens identify keloid susceptibility loci on chromosomes 2q23 and 7p11.
• J Invest. Dermatol, 2004;122(5):1126-1132.
• Marneros AG and Olsen BR. Age-dependent iris abnormalities in collagen XVIII/endostatin deficient mice with similarities to human pigment dispersion syndrome. Invest Ophthalmol Vis Sci. 2003;44(6):2367-72.
• Fukai N*, Eklund L*, Marneros AG*, Oh SP, Keene DR, Tamarkin L, Niemela M, Ilves M, Li E, Pihlajaniemi T, Olsen BR. Lack of collagen XVIII/endostatin results in eye abnormalities. EMBO J. 2002 Apr 2;21(7):1535-44. *equal contribution.
• Marneros AG, Norris JEC, Olsen BR, Reichenberger E. Clinical genetics of familial keloids. Archives of Dermatology. 2001;137(11):1429-34.
• Marneros AG, Olsen BR. The role of collagen-derived proteolytic fragments in angiogenesis. Matrix Biology, 2001; 20(5-6):337-345.

Alexander G. Marneros, M.D., Ph.D.

Phone: 617-643-7170
Fax: 617-726-2120
Email: amarneros@partners.org

Public Transportation Access: yes
Disabled Access: yes