Explore This Lab


Our laboratory is interested in mechanisms that affect wound healing, epithelial biology, inflammation, angiogenesis and fibrosis. Our work has a particular focus on how these processes affect age-related diseases, such as age-related macular degeneration or chronic kidney disease.

News from Our Laboratory

  1. June 17, 2020:  Identification of a critical role of AP-2b and KCTD1 for kidney development and renal fibrosis, now published in Developmental Cell.

    We show that the transcription factor AP-2b induces differentiation of distal tubule precursors into early stage distal convoluted tubules (DCTs), whereas its downstream target KCTD1 is required for their terminal differentiation into mature DCTs. KCTD1 loss causes immature DCTs, leading to a salt-losing tubulopathy followed by renal fibrosis via b-catenin hyperactivation. 

    “AP-2b/KCTD1 Control Distal Nephron Differentiation and Protect against Renal Fibrosis”, Developmental Cell (2020), https://doi.org/10.1016/j.devcel.2020.05.026

    Mass General press release

  2. Our Laboratory receives for second time competitive Age-related Macular Degeneration Research Award from the BrightFocus foundation.
  3. Our laboratory receives two new NIH R01 grants to study novel mechanisms in kidney development and renal fibrosis. 

Research Projects

Abnormal blood vessel growth is an important component in the pathogenesis of various common diseases. Pathological angiogenesis is stimulated by an inflammatory response that involves many different cell types, including proangiogenic macrophages. The Laboratory for Angiogenesis, Wound Healing and Inflammation at Massachusetts General Hospital focuses on the factors and cell types that promote pathologic angiogenesis in development, in the adult and during aging.

Abnormal Angiogenesis During Aging: Age-Related Macular Degeneration

Abnormal blood vessel growth is an important component in the pathogenesis of various common diseases. Pathological angiogenesis is stimulated by an inflammatory response that involves many different cell types, including proangiogenic macrophages. We are studying the pathomechanisms that promote pathologic angiogenesis in development, in the adult and during aging.

Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in the elderly. Non-exudative (dry) AMD manifests with degeneration of the retinal pigment epithelium (RPE) and sub-RPE deposit formation with progressive age. Neovascular (wet) AMD manifests with pathologic neovascularization from the choroid into the retina. Often both forms co-occur, suggesting a common pathomechanism. We have recently shown in a new mouse model of AMD that increased VEGF-A is sufficient to cause both forms of AMD, providing evidence for a unifying pathomechanism in advanced AMD. In this model, proangiogenic macrophages stimulate retinal glia cells to promote choroidal neovascularization. Furthermore, we could show that the NLRP3 inflammasome promotes VEGF-A-induced AMD pathologies and targeting inflammasome components inhibits these pathologies. This project focuses on elucidating the mechanisms that regulate molecular pathways and cellular interactions during AMD pathogenesis, with the aim of identifying novel therapeutic approaches for patients with AMD.

Role of Macrophages in Angiogenesis and the Wound Healing Response

Multiple cell types interact in a highly coordinated fashion in response to injury to promote wound healing. Abnormalities in this complex process can result in exuberant wound angiogenesis or scarring. We use in vivo models of wound healing to determine the spatiotemporal contributions of various cell types in this process. In a laser-injury model of choroidal neovascularization, we could show that macrophages become alternatively activated (M2-type) and promote wound angiogenesis, in part by stimulating retinal glia cells to express proangiogenic growth factors. Specific ablation of macrophages inhibits the early wound healing response to injury and blocks wound angiogenesis. Our current research investigates which signaling pathways drive polarization of macrophages to the proangiogenic M2-type in vivo and how this polarization can be inhibited. Overall, the project aims to define the contributions of individual inflammatory cell populations to wound healing and neovascularization.

Regulation of Skin Formation During Development: Causes of Congenital Wounds

chart: autosomal dominant aplasia
Autosomal dominant aplasia cutis congenita is caused by a mutation in the ribosomal biogenesis GTPase BMS1. The mutation results in a maturation defect of the small ribosomal subunit and a p21‐mediated nucleolar stress response that leads to a reduced cell proliferation rate (PLoS Genet. 2013; 9(6):e1003573).

Wound healing and wound angiogenesis occur in response to injury. However, congenital wounds are observed in various genetic syndromes as a manifestation of a skin morphogenesis defect during embryonic development. Identifying the genetic basis for these conditions and syndromes promises to identify novel genes and pathways that are critical for proper skin formation and whose impairment results in wounds. A prototypical congenital skin disease that manifests with a wound present at birth is aplasia cutis congenita (ACC). Using a combination of genome-wide linkage analysis and exome sequencing, we recently identified the causative mutation for ACC. We found that the ribosomal GTPase BMS1 is mutated in ACC, which results in a maturation defect of the small ribosomal subunit and leads to a nucleolar stress response with a p21-mediated G1/S phase transition delay and a reduced cell proliferation rate. Global proteomic and transcriptional analyses revealed a central role of p21 activation for the ACC phenotype.

Our laboratory investigates how a mutation in a ubiquitous ribosomal protein leads to localized skin defects without affecting other organ systems. We seek to obtain a comprehensive understanding of the disease mechanisms of congenital wound healing disorders.

Epithelial Differentiation Mechanisms in the Kidney: Role for Chronic Kidney Disease, Renal Fibrosis and Cyst Formation

Our studies on epidermal morphogenesis in the skin have led us to assess molecular mechanisms that control epithelial differentiation in other epithelial tissues, particularly the kidney. We identified novel regulators of the epithelial differentiation process of the nephron, which have previously not been considered to affect kidney function. Using mouse genetics approaches we are aiming to define the molecular mechanisms that control epithelial differentiation in the kidney during development and in the adult. We also aim to determine how epithelial defects in the kidney may contribute to renal fibrosis and cyst formation. 

Research Positions

A position for a highly dedicated and qualified postdoctoral research fellow is currently available.

Our laboratory utilizes diverse experimental techniques and has long-standing expertise in mouse genetics, molecular biology, and imaging techniques.  We are embedded with a highly interactive  excellent research environment  at Massachusetts General Hospital and Harvard Medical School.

Our research projects involve epithelial biology, wound healing, angiogenesis and inflammation. This allows exposure to diverse but overlapping areas of research. Much of our work has clinical and translational relevance.


1. PhD with at least one significant first author publication (at least accepted for publication)

2. Expertise in molecular biology techniques

3. Working well within a team, excellent work ethic and being well organized.

Alexander Marneros, MD/PhD
Associate Professor, Harvard Medical School
Massachusetts General Hospital



Slides from the Marneros Lab

Lab Members


Lizhi (Justin) He, PhD: Postdoctoral research fellow
Joseph Lamontagner: research technician
Alia Zeid:  research technician
Sheryl Zhang: research technician
Andrea Alvarado: student
Jakob Malsy: student


Selected Publications

Marneros AG. AP-2b/KCTD1 Control Distal Nephron Differentiation and Protect against Renal Fibrosis, Developmental Cell. 2020, https://doi.org/10.1016/j.devcel.2020.05.026

Marneros AG. Effects of chronically increased VEGF-A on the aging heart. Am J Pathol. 2018 Mar;32(3):1550-1565. doi: 10.1096/fj.201700761RR.

Strittmatter K, Pomeroy H, Marneros AG. Targeting PDGFRβ+ scaffold formation inhibits choroidal neovascularization. Am J Pathol. 2016, 186(7):1890-9.

Marneros AG. Increased VEGF-A promotes multiple distinct aging diseases of the eye through shared pathomechanisms. EMBO Mol Med. 2016, 8(3): 208-231. PMID: 26912740.

Marneros, AG. Genetics of aplasia cutis reveal novel regulators of skin morphogenesis. J Invest Dermatol. 2015, 135(3):666-672. PMID: 25355129.

Ablonczy Z, Dahrouj M, Marneros AG.Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF-A levels. FASEB J. 2014, May;28(5):2369-79. doi: 10.1096/fj.13-248021.

He L, Marneros AG. Doxycycline inhibits polarization of macrophages to the proangiogenic M2-type and subsequent neovascularization. J Biol Chem. 2014, Mar 21;289(12):8019-28. doi: 10.1074/jbc.M113.535765.

He L, Marioutina M, Dunaieff J, Marneros AG. Age- and gene dosage-dependent Cre-mediated abnormalities in the retinal pigment epithelium. Am J Pathol. 2014, Jun;184(6):1660-7. doi: 10.1016/j.ajpath.2014.02.007.

Marneros AG. NLRP3 Inflammasome Blockade Inhibits VEGF-A-Induced Age-Related Macular Degeneration. Cell Reports. 2013, 4(5): 945-958. Cover article.

He L, Marneros AG. Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar. Am J.Pathol. 2013 182(6):2407-17 Cover article.

Marneros AG. BMS1 is mutated in Aplasia Cutis Congenita. Plos Genetics. 2013, 9(6):e1003573.

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, 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, 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, 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, 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.

Full publication list for Marneros AG[au]