Esteban Carlos Dell'Angelica

Laboratory Address:
Gonda 6554
Los Angeles, CA 90095

Office Address:
Gonda 6554A
Los Angeles, CA 90095

Professor, Human Genetics
Member, Genetics & Genomics GPB Home Area, Human Genetics
Research Interests
The overarching goal of my research is to understand the molecular pathogenesis of monogenic disorders such as Hermansky-Pudlak syndrome (HPS). HPS comprises a group of autosomal-recessive diseases characterized by albinism and prolonged bleeding due to deficiencies in two specialized intracellular organelles: melanosomes (the site of synthesis and storage of melanin pigments) and platelet dense granules (the storage compartment for some of the molecules involved in platelet aggregation). Both melanosomes and platelet dense granules are referred to as ‘lysosome-related’ organelles. All of the genes known to be mutated in different forms of HPS encode subunits of four heteromeric, biochemically stable protein complexes: Adaptor Protein (AP)-3, and Biogenesis of Lysosome-related Organelles Complex (BLOC)-1 through -3. Using a variety of experimental approaches, including biochemical and cell biological assays as well as mouse and fly genetics, we are characterizing the biological function of these protein complexes.

Esteban C. Dell'Angelica got his Ph.D. degree at the University of Buenos Aires (Argentina) for his isolation and biochemical characterization of a hitherto unknown calcium-binding protein from neutrophils. During his postdoctoral training in the laboratory of Juan S. Bonifacino, Ph.D., at the National Institutes of Health (Bethesda, Maryland), he identified and characterized several components of the molecular machinery for protein trafficking within the so-called ‘late secretory’ and ‘endocytic’ intracellular pathways, and he described the first example of human disease due to mutations in a known component of such molecular machinery (Hermansky-Pudlak syndrome type 2). As a junior faculty at UCLA, he identified and characterized three multi-subunit protein complexes, named BLOC-1 through -3, which are required for the biogenesis of lysosome-related organelles such as melanosomes and platelet dense granules. For a complete list of publications, please see:'Angelica%5Bauthor%5D

Rodriguez-Fernandez IA, Dell'Angelica EC. Identification of Atg2 and ArfGAP1 as Candidate Genetic Modifiers of the Eye Pigmentation Phenotype of Adaptor Protein-3 (AP-3) Mutants in Drosophila melanogaster. PLoS One. 2015; 10: e0143026.
Bultema JJ, Boyle JA, Malenke PB, Martin FE, Dell'Angelica EC, Cheney RE, Di Pietro SM. Myosin Vc interacts with Rab32 and Rab38 proteins and works in the biogenesis and secretion of melanosomes. The Journal of Biological Chemistry. 2014; 289: 33513-33528.
Arboleda VA, Lee H, Parnaik R, Fleming A, Banerjee A, Ferraz-de-Souza B, Delot EC, Rodriguez-Fernandez IA, Braslavsky D, Bergada I, Dell'Angelica EC, Nelson SF, Martinez-Agosto JA, Achermann JC, Vilain E. Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nature Genetics. 2012; 44: 788-792.
Ghiani CA, Dell'Angelica EC. Dysbindin-containing complexes and their proposed functions in brain: from zero to (too) many in a decade. ASN Neuro. 2011; 3: e00058.
Hoyle DJ, Rodriguez-Fernandez IA, Dell'Angelica EC. Functional interactions between OCA2 and the protein complexes BLOC-1, BLOC-2 and AP-3 inferred from epistatic analyses of mouse coat pigmentation. Pigment Cell & Melanoma Research. 2011; 24: 275-281.
Cheli VT, Daniels RW, Godoy R, Hoyle DJ, Kandachar V, Starcevic M, Martinez-Agosto JA, Poole S, Diantonio A, Lloyd VK, Chang HC, Krantz DE, Dell'Angelica EC. Genetic modifiers of abnormal organelle biogenesis in a Drosophila model of BLOC-1 deficiency. Human Molecular Genetics. 2010; 19: 861-878.
Cheli VT, Dell'Angelica EC. Early origin of genes encoding subunits of biogenesis of lysosome-related organelles complex (BLOC)-1, -2 and -3. Traffic. 2010; 11: 579-586.
Ghiani CA, Starcevic M, Rodriguez-Fernandez IA, Nazarian R, Cheli VT, Chan LN, Malvar JS, de Vellis J, Sabatti C, Dell'Angelica EC. The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth. Molecular Psychiatry. 2010; 15: 204?215.
Rodriguez-Fernandez IA, Dell'Angelica EC. A data-mining approach to rank candidate protein-binding partners--The case of biogenesis of lysosome-related organelles complex-1 (BLOC-1). Journal of Inherited Metabolic Disorders. 2009; 32: 190-203.
Dell'Angelica EC. AP-3-dependent trafficking and disease: the first decade. Current Opinion in Cell Biology. 2009; 21: 552-559.
Nazarian R, Huizing M, Helip-Wooley A, Starcevic M, Gahl WA, Dell'Angelica EC. An immunoblotting assay to facilitate the molecular diagnosis of Hermansky-Pudlak syndrome. Molecular Genetics and Metabolism. 2008; 93: 134-144.
Falcon-Perez JM, Dell'Angelica EC. Zinc transporter 2 (SLC30A2) can suppress the vesicular zinc defect of adaptor protein 3-depleted fibroblasts by promoting zinc accumulation in lysosomes. Experimental Cell Research. 2007; 313: 1473-1483.
Falcon-Perez JM, Romero-Calderon R, Brooks ES, Krantz DE, Dell'Angelica EC. The Drosophila pigmentation gene pink (p) encodes a homologue of human Hermansky-Pudlak syndrome 5 (HPS5). Traffic. 2007; 15: 154-168.
Di Pietro SM, Falcon-Perez JM, Tenza D, Setty SRG, Marks MS, Raposo G, Dell'Angelica EC. BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Molecular Biology of the Cell. 2006; 17: 4027-4038.
Nazarian R, Starcevic M, Spencer MJ, Dell'Angelica EC. Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) as a dystrobrevin-binding protein. Biochemical Journal. 2006; 395: 587-598.
Falcon-Perez JM, Nazarian R, Sabatti C, Dell'Angelica EC. Distribution and dynamics of Lamp1-containing endocytic organelles in fibroblasts deficient in biogenesis of lysosome-related organelles complex-3 (BLOC-3). The Journal of Cell Science. 2005; 118: 5243-5255.
Starcevic M, Dell'Angelica EC. Identification of snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1). The Journal of Biological Chemistry. 2004; 279: 28393-28401.
Di Pietro SM, Falcon-Perez JM, Dell'Angelica EC. Characterization of BLOC-2, a complex containing the Hermansky-Pudlak syndrome proteins HPS3, HPS5 and HPS6. Traffic. 2004; 5: 276-283.
Nazarian R, Falcon-Perez JM, Dell'Angelica EC. Biogenesis of lysosome-related organelles complex 3 (BLOC-3): A complex containing the Hermansky-Pudlak syndrome (HPS) proteins HPS1 and HPS4. Proceedings of the National Academy of Sciences USA. 2003; 100: 8770-8775.
Falcon-Perez JM, Starcevic M, Gautam R, Dell'Angelica EC. BLOC-1, a novel complex containing the pallidin and muted proteins involved in the biogenesis of melanosomes and platelet dense granules. The Journal of Biological Chemistry. 2002; 277: 28191-28199.