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695 Charles E. Young Dr. South
Los Angeles, CA 90095
695 Charles E. Young Drive South
Los Angeles, CA 90095
Division of Medical Genetics
Department of Pediatrics
David Geffen School of Medicine at UCLA
10833 LeConte Avenue, CHS 32-231
Los Angeles, CA 90095
|Assistant Professor, Pediatrics, Pediatric Genetics, Medical Genetics Clinic, Human Genetics|
|Member, CTSI, Cell & Developmental Biology GPB Home Area, Genetics & Genomics GPB Home Area, JCCC Signal Transduction and Therapeutics Program Area|
Our research program focuses on the molecular regulation of stem cell progenitors. The major areas of investigation are:
1. In vivo regulation of niche-stem cell interactions
2. Adult tissue reprogramming and regeneration
3. Genetic models of cancer predisposition syndromes
In vivo regulation of niche-stem cell interactions
As one of the first somatic stem cells isolated, HSC transplantation has become a therapeutic intervention for many pediatric diseases, including leukemias. A major challenge has been isolating HSC and expanding them in culture due to the requirement of signals from a niche for their maintenance. Limitations in our understanding of the molecular basis of these niche-stem cell interactions have constrained our ability to expand these cells ex vivo and reduce the need for bone marrow donation.
We have previously described the presence of a hematopoietic niche within the Drosophila larva. Our goal is to define the niche-derived signals required for maintenance of stemness versus cell differentiation in a population of blood stem-like precursors as a framework for understanding the biology of vertebrate hematopoietic stem cell niche function. In particular we focus on how a stem cell niche is established and its identity maintained. Through in vivo genetic screens and in vitro assays of cultured blood cell precursors, we seek to identify novel pathways which regulate the formation of niche cells and which maintain their identity as signaling cells required for the maintenance of hematopoietic progenitors in the Drosophila lymph gland.
In addition, we utilize lineage tracing and label retention techniques to identify novel stem cell niches in which to model human disease.
Adult tissue reprogramming and regeneration
We seek to understand the process of tissue regeneration as a model for the reprogramming of adult tissues. We hypothesize that by reactivating developmental programs characteristic of tissue-specific stem-like progenitors, through epigenetic and transcriptional manipulations, we can promote regeneration and tissue repair.
Genetic models of cancer predisposition syndromes
We are interested in understanding the common signal transduction pathways across cancer predisposition genetic syndromes and their associated malignancies: neuroblastoma, sarcomas, and myeloproliferative disorders. To this end we utilize several approaches:
1. We use Drosophila melanogaster as a model organism in which to model the cellular and genetic mechanisms that lead to oncogenesis and the role of stem cell niches in cancer predisposition.
2. We pursue translational developmental biology by performing small molecule compound screens in vivo (Drosophila larval screens) and in vitro (stem cell cultures) to identify therapies for these pediatric cancers and genetic syndromes.
3. We utilize whole genome sequencing approaches to identify genes that cause overgrowth as well as macrocephaly-autism syndromes.
Julian A. Martinez-Agosto is a medical geneticist and developmental biologist who has served on the UCLA School of Medicine faculty since he joined the Department of Human Genetics in 2007. Dr. Martinez earned his B.S. in Biology and Spanish Literature at Yale University and pursued his medical training at Yale School of Medicine. He went on to train as a Pediatrician at Mattel Children's Hospital UCLA. Dr. Martinez-Agosto was Chief Resident of the UCLA Intercampus Medical Genetics Program, where he trained as and currently is a board certified Medical Geneticist. He was a postdoctoral fellow in the laboratory of Utpal Banerjee at UCLA, where he worked on blood cell development in Drosophila. Dr. Martinez is a recipient of the Pediatric Department Outstanding Research Award, as well as the David W. Smith Pediatric Trainee Research Award of the Western Society for Pediatric Research, among other honors. Dr. Martinez-Agosto is a member of the Division of Medical Genetics, where he has maintained a clinical interest in genetic syndromes that lead to overgrowth, vascular malformations, and cancer predisposition. His laboratory research focuses on novel growth regulatory pathways in progenitor and stem cell maintenance and the study of human growth disorders with cancer predisposition.
Martinez-Agosto Julian A, Mikkola Hanna K A, Hartenstein Volker, Banerjee Utpal The hematopoietic stem cell and its niche: a comparative view. Genes & development. 2007; 21(23): 3044-60.
Quintero-Rivera Fabiola, Sharifi-Hannauer Pantea, Martinez-Agosto Julian A Autistic and psychiatric findings associated with the 3q29 microdeletion syndrome: case report and review. American journal of medical genetics. Part A. 2010; 152A(10): 2459-67.
Martinez Agosto Julian A, McCabe Edward R B Conserved family of glycerol kinase loci in Drosophila melanogaster. Molecular genetics and metabolism. 2006; 88(4): 334-45.
Mandal Lolitika, Martinez-Agosto Julian A, Evans Cory J, Hartenstein Volker, Banerjee Utpal A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors. Nature. 2007; 446(7133): 320-4.
Cheli VerÃ³nica T, Daniels Richard W, Godoy Ruth, Hoyle Diego J, Kandachar Vasundhara, Starcevic Marta, Martinez-Agosto Julian A, Poole Stephen, DiAntonio Aaron, Lloyd Vett K, Chang Henry C, Krantz David E, Dell'Angelica Esteban C Genetic modifiers of abnormal organelle biogenesis in a Drosophila model of BLOC-1 deficiency. Human molecular genetics. 2010; 19(5): 861-78.
Mondal Bama Charan, Mukherjee Tina, Mandal Lolitika, Evans Cory J, Sinenko Sergey A, Martinez-Agosto Julian A, Banerjee Utpal Interaction between Differentiating Cell- and Niche-Derived Signals in Hematopoietic Progenitor Maintenance. Cell. 2011; 147(7): 1589-600.
Sinenko Sergey A, Mandal Lolitika, Martinez-Agosto Julian A, Banerjee Utpal Dual role of wingless signaling in stem-like hematopoietic precursor maintenance in Drosophila. Developmental cell. 2009; 16(5): 756-63.
Chang Vivian Y, Quintero-Rivera Fabiola, Baldwin Erin E, Woo Kathy, Martinez-Agosto Julian A, Fu Cecilia, Gomperts Brigitte N B-acute lymphoblastic leukemia and cystinuria in a patient with duplication 22q11.21 detected by chromosomal microarray analysis. Pediatric blood & cancer. 2011; 56(3): 470-3.
Bui Yen K, Renella Pierangelo, Martinez-Agosto Julian A, Verity Anthony, Madikians Andranik, Alejos Juan C Danon disease with typical early-onset cardiomyopathy in a male: focus on a novel LAMP-2 mutation. Pediatric transplantation. 2008; 12(2): 246-50.
Quintero-Rivera Fabiola, Martinez-Agosto Julian A Bilateral exophthalmos: Report of a case and review of a fibroblast growth factor receptor 2 mutation associated with non-penetrant Crouzon syndrome. Journal of paediatrics and child health. 2010; 46(11): 693-5.
Tieu Kevin S, Tieu Ryan S, Martinez-Agosto Julian A, Sehl Mary E Stem cell niche dynamics: from homeostasis to carcinogenesis. Stem cells international. 2012; 2012(7): 367567.
Lu Ake Tzu-Hui, Dai Xiaoxian, Martinez-Agosto Julian A, Cantor Rita M Support for calcium channel gene defects in autism spectrum disorders. Molecular autism. 2012; 3(1): 18.
Dragojlovic-Munther Michelle, Martinez-Agosto Julian A Multifaceted roles of PTEN and TSC orchestrate growth and differentiation of Drosophila blood progenitors. Development (Cambridge, England). 2012; 139(20): 3752-63.
Dragojlovic-Munther Michelle, Martinez-Agosto Julian A Extracellular matrix-modulated Heartless signaling in Drosophila blood progenitors regulates their differentiation via a Ras/ETS/FOG pathway and target of rapamycin function. Developmental biology. 2013; .
Klein Steven, Stroberg Albert, Ghahremani Shahnaz, Martinez-Agosto Julian A Phenotypic progression of skeletal anomalies in CLOVES syndrome. American journal of medical genetics. Part A. 2012; 158A(7): 1690-5.
Chang Vivian Y, Federman Noah, Martinez-Agosto Julian, Tatishchev Sergei F, Nelson Stanley F Whole exome sequencing of pediatric gastric adenocarcinoma reveals an atypical presentation of Li-Fraumeni syndrome. Pediatric blood & cancer. 2013; 60(4): 570-4.
Arboleda Valerie A, Lee Hane, Parnaik Rahul, Fleming Alice, Banerjee Abhik, Ferraz-de-Souza Bruno, DÃ©lot EmmanuÃ¨le C, Rodriguez-Fernandez Imilce A, Braslavsky Debora, BergadÃ¡ Ignacio, Dell'Angelica Esteban C, Nelson Stanley F, Martinez-Agosto Julian A, Achermann John C, Vilain Eric Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nature genetics. 2012; 44(7): 788-92.
Klein Steven, Sharifi-Hannauer Pantea, Martinez-Agosto Julian A Macrocephaly as a clinical indicator of genetic subtypes in autism. Autism research : official journal of the International Society for Autism Research. 2013; 6(1): 51-6.
Quintero-Rivera Fabiola, Martinez-Agosto Julian A Hemifacial microsomia in cat-eye syndrome: 22q11.1-q11.21 as candidate loci for facial symmetry. American journal of medical genetics. Part A. 2013; 161A(8): 1985-91.