Ana Paula Azambuja

@cornell.edu

Researcher Department of Molecular Biology and Genetics
Cornell University

Ana Paula Azambuja


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https://researchid.co/anaazambuja
22

Scopus Publications

769

Scholar Citations

13

Scholar h-index

15

Scholar i10-index

Scopus Publications

  • Spatial patterning of the epigenome during vertebrate gastrulation
    Ana Paula Azambuja, Megan Rothstein, Tatiane Y. Kanno, Marcos Simoes-Costa
    Nature Communications, 2026
    A central question in developmental biology is how embryonic cells acquire and store positional information during pattern formation. In vertebrates, this process begins with the localized activation of signaling systems that mediate axial specification. How these spatial cues are recorded within the regulatory landscape of cells has remained unclear. Here, we report that the chromatin landscape of embryonic cells is spatially patterned during gastrulation. Using spatially resolved genomic analysis in avian embryos, we observed that the epigenome becomes organized in gradients of accessibility and activity along the embryonic axes. These chromatin gradients are established within the loci of developmental genes at the onset of gastrulation and can be used to infer the position of cells in the embryo. Our results show that axial specification involves the spatial organization of the epigenome, linking patterns of chromatin activity to the emergence of the embryonic body plan. Embryonic patterning requires generation of positional information that defines where cells reside within the embryo. Here, Azambuja, Rothstein and colleagues report that the epigenome is spatially patterned during early development, showing that chromatin organization reflects the embryo’s emerging body plan.
  • A modular enhancer mediates SCRT2 repression of ISLET1 in the spinal cord
    Vitória S. Botezelli, Tatiane Y. Kanno, Ee Shan Liau, Carolina P. Goes, Shirley de La Cruz Anticona, Ana Paula Azambuja, Marcos Simoes-Costa, C.Y. Irene Yan
    Developmental Biology, 2025
  • TGF-β signaling controls neural crest developmental plasticity via SMAD2/3
    Megan Rothstein, Ana Paula Azambuja, Tatiane Y. Kanno, Catriona Breen, Marcos Simoes-Costa
    Developmental Cell, 2025
  • Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis
    Derek Dang, Akash Deogharkar, John McKolay, Kyle S. Smith, Pooja Panwalkar, Simon Hoffman, Wentao Tian, Sunjong Ji, Ana P. Azambuja, Siva Kumar Natarajan, Joanna Lum, Jill Bayliss, Katie Manzeck, Stefan R. Sweha, Erin Hamanishi, Matthew Pun, Diya Patel, Sagar Rau, Olamide Animasahun, Abhinav Achreja, Martin P. Ogrodzinski, Jutta Diessl, Jennifer Cotter, Debra Hawes, Fusheng Yang, Robert Doherty, Andrea T. Franson, Allison R. Hanaford, Charles G. Eberhart, Eric H. Raabe, Brent A. Orr, Robert J. Wechsler-Reya, Brandon Chen, Costas A. Lyssiotis, Yatrik M. Shah, Sophia Y. Lunt, Ruma Banerjee, Alexander R. Judkins, John R. Prensner, Carl Koschmann, Sebastian M. Waszak, Deepak Nagrath, Marcos Simoes-Costa, Paul A. Northcott, Sriram Venneti
    Cancer Cell, 2025
  • ASCL1 promotes Scrt2 expression in the neural tube
    Carolina Purcell Goes, Vitória Samartin Botezelli, Shirley Mirna De La Cruz, Mário Costa Cruz, Ana Paula Azambuja, Marcos Simoes-Costa, Chao Yun Irene Yan
    Frontiers in Cell and Developmental Biology, 2024
    ASCL1 is a transcription factor that directs neural progenitors towards lineage differentiation. Although many of the molecular mechanisms underlying its action have been described, several of its targets remain unidentified. We identified in the chick genome a putative enhancer (cE1) upstream of the transcription factor Scratch2 (Scrt2) locus with a predicted heterodimerization motif for ASCL1 and POU3F2. In this study, we investigated the role of ASCL1 and this enhancer in regulating the expression of the Scrt2 in the embryonic spinal cord. We confirmed that cE1 region interacted with the Scrt2 promoter. cE1 was sufficient to mediate ASCL1-driven expression in the neural tube through the heterodimerization sites. Moreover, Scrt2 expression was inhibited when we removed cE1 from the genome. These findings strongly indicate that ASCL1 regulates Scrt2 transcription in the neural tube through cE1.
  • Pluripotency factors are repurposed to shape the epigenomic landscape of neural crest cells
    Austin S. Hovland, Debadrita Bhattacharya, Ana Paula Azambuja, Dimitrius Pramio, Jacqueline Copeland, Megan Rothstein, Marcos Simoes-Costa
    Developmental Cell, 2022
  • The connectome of neural crest enhancers reveals regulatory features of signaling systems
    Ana Paula Azambuja, Marcos Simoes-Costa
    Developmental Cell, 2021
    Cell fate commitment is controlled by cis-regulatory elements often located in remote regions of the genome. To examine the role of long-range DNA interactions in early development, we generated a high-resolution contact map of active enhancers in avian neural crest cells. This analysis uncovered a diverse repertoire of enhancers that are part of the gene regulatory network underlying specification. We found that neural crest identity is largely regulated by cis-regulatory elements that propagate signaling inputs to network components. These genomic sensors display a combination of optimal and suboptimal TCF/LEF-binding sites, which allow cells to respond to Wnt signaling in a position-dependent manner. We propose that, rather than acting as upstream activators, signaling systems feed into regulatory circuits in a hub-and-spoke architecture. These results shed light on the tridimensional organization of the neural crest genome and define how signaling systems provide progenitors with spatial cues that transform their molecular identity.
  • A regulatory sub-circuit downstream of Wnt signaling controls developmental transitions in neural crest formation
    Ana Paula Azambuja, Marcos Simoes-Costa
    Plos Genetics, 2021
    The process of cell fate commitment involves sequential changes in the gene expression profiles of embryonic progenitors. This is exemplified in the development of the neural crest, a migratory stem cell population derived from the ectoderm of vertebrate embryos. During neural crest formation, cells transition through distinct transcriptional states in a stepwise manner. The mechanisms underpinning these shifts in cell identity are still poorly understood. Here we employ enhancer analysis to identify a genetic sub-circuit that controls developmental transitions in the nascent neural crest. This sub-circuit links Wnt target genes in an incoherent feedforward loop that controls the sequential activation of genes in the neural crest lineage. By examining the cis-regulatory apparatus of Wnt effector gene AXUD1, we found that multipotency factor SP5 directly promotes neural plate border identity, while inhibiting premature expression of specification genes. Our results highlight the importance of repressive interactions in the neural crest gene regulatory network and illustrate how genes activated by the same upstream signal become temporally segregated during progressive fate restriction.
  • Metabolic Reprogramming Promotes Neural Crest Migration via Yap/Tead Signaling
    Debadrita Bhattacharya, Ana Paula Azambuja, Marcos Simoes-Costa
    Developmental Cell, 2020
    The Warburg effect is one of the metabolic hallmarks of cancer cells, characterized by enhanced glycolysis even under aerobic conditions. This physiological adaptation is associated with metastasis , but we still have a superficial understanding of how it affects cellular processes during embryonic development. Here we report that the neural crest, a migratory stem cell population in vertebrate embryos, undergoes an extensive metabolic remodeling to engage in aerobic glycolysis prior to delamination. This increase in glycolytic flux promotes Yap/Tead signaling, which activates the expression of a set of transcription factors to drive epithelial-to-mesenchymal transition. Our results demonstrate how shifts in carbon metabolism can trigger the gene regulatory circuits that control complex cell behaviors. These findings support the hypothesis that the Warburg effect is a precisely regulated developmental mechanism that is anomalously reactivated during tumorigenesis and metastasis.
  • Identifying protein-DNA and protein-protein interactions in avian embryos
    Ana Paula Azambuja, Marcos Simoes-Costa
    Methods in Molecular Biology, 2019
    The chick embryo is a powerful model for experimental embryology due to its accessibility, sturdiness, and ease of manipulation. Here we describe protocols for analysis of protein-DNA and protein-protein interactions in tissues and cells isolated from the developing chick. These assays are aimed at the identification of interactions between transcription factors and regulatory elements in the genome, and, in combination with functional assays, can be used for the delineation of gene regulatory circuits.
  • Control of neural crest multipotency by wnt signaling and the Lin28/let-7 axis
    Debadrita Bhattacharya, Megan Rothstein, Ana Paula Azambuja, Marcos Simoes-Costa
    Elife, 2018
  • Development of the Coronary System: Perspectives for Cell Therapy From Precursor Differentiation
    Alexander R. Moise, Ângela M.S. Costa, Murilo Carvalho, Ana P. Azambuja, José Xavier-Neto, Hozana A. Castillo
    Endothelium and Cardiovascular Diseases Vascular Biology and Clinical Syndromes, 2018
  • Cohort profile: The Baependi Heart Study - A family-based, highly admixed cohort study in a rural Brazilian town
    Kieren J Egan, Malcolm von Schantz, André B Negrão, Hadassa C Santos, Andréa R V R Horimoto, Nubia E Duarte, Guilherme C Gonçalves, Júlia M P Soler, Mariza de Andrade, Geraldo Lorenzi-Filho, Homero Vallada, Tâmara P Taporoski, Mario Pedrazzoli, Ana P Azambuja, Camila M de Oliveira, Rafael O Alvim, José E Krieger, Alexandre C Pereira
    BMJ Open, 2016
  • A population-based study of the stratum corneum moisture
    Thiago Pires, Ana Paula Azambuja, Andrea Horimoto, Mary Veroneze, Rafael Alvim, Jose Eduardo Krieger, Alexandre Pereira
    Clinical Cosmetic and Investigational Dermatology, 2016
  • Repulsive Guidance Molecules a, b and c Are Skeletal Muscle Proteins, and Repulsive Guidance Molecule a Promotes Cellular Hypertrophy and Is Necessary for Myotube Fusion Aline Fagundes Martins1
    Aline Fagundes Martins, José Xavier Neto, Ana Azambuja, Maria Lorena Sereno, Antonio Figueira, Paulo Henrique Campos-Junior, Millor Fernandes Rosário, Cristiane Bittencourt Barroso Toledo, Gerluza Aparecida Borges Silva, Gregory Thomas Kitten, Luiz Lehmann Coutinho, Susanne Dietrich, Erika Cristina Jorge
    Cells Tissues Organs, 2015
  • Relationship between anthropometric and hemodynamic indexes in school children
    Ana Paula De Oliveira Azambuja, Edna Regina Netto-Oliveira, Amauri Aparecido Bássoli de Oliveira, Maximiliano Dos Anjos Azambuja, Wilson Rinaldi
    Acta Scientiarum Health Sciences, 2014
  • Prevalence of overweight/obesity and economical status of schoolchildren
    Ana Paula de O. Azambuja, Edna Regina Netto-Oliveira, Amauri Aparecido B. de Oliveira, Maximiliano dos Anjos Azambuja, Wilson Rinaldi
    Revista Paulista De Pediatria, 2013
  • Evolutionary Origins of Hearts
    José Xavier-Neto, Brad Davidson, Marcos Sawada Simoes-Costa, Rodrigo Abe Castro, Hozana Andrade Castillo, Allysson Coelho Sampaio, Ana Paula Azambuja
    Heart Development and Regeneration, 2010
  • Retinoic acid and VEGF delay smooth muscle relative to endothelial differentiation to coordinate inner and outer coronary vessel wall morphogenesis
    Ana P. Azambuja, Victor Portillo-Sánchez, Mariliza V. Rodrigues, Samantha V. Omae, Deborah Schechtman, Bryan E. Strauss, Eugenia Costanzi-Strauss, José E. Krieger, José M. Perez-Pomares, José Xavier-Neto
    Circulation Research, 2010
  • Insights into the organization of dorsal spinal cord pathways from an evolutionarily conserved raldh2 intronic enhancer
    H. A. Castillo, R. M. Cravo, A. P. Azambuja, M. S. Simoes-Costa, S. Sura-Trueba, J. Gonzalez, E. Slonimsky, K. Almeida, J. G. Abreu, M. A. A. de Almeida, T. P. Sobreira, S. H. P. de Oliveira, P. S. L. de Oliveira, I. A. Signore, A. Colombo, M. L. Concha, T. S. Spengler, M. Bronner-Fraser, M. Nobrega, N. Rosenthal, J. Xavier-Neto
    Development, 2010
  • The search for non-chordate retinoic acid signaling: Lessons from chordates
    Marcos S. Simões-costa, Ana Paula Azambuja, José Xavier-Neto
    Journal of Experimental Zoology Part B Molecular and Developmental Evolution, 2008
  • Cardiovascular development: Towards biomedical applicability - Parallel avenues in the evolution of hearts and pumping organs
    J. Xavier-Neto, R. A. Castro, A. C. Sampaio, A. P. Azambuja, H. A. Castillo, R. M. Cravo, M. S. Simões-Costa
    Cellular and Molecular Life Sciences, 2007

RECENT SCHOLAR PUBLICATIONS

  • ALK-specific TCR-T cells showed potent and specific activity in ALK-positive anaplastic large cell lymphoma
    S Piane, C Mecca, NT Pun, A Azambuja, L Alessandri, PB Nguyen, ...
    Cancer Research 86 (7_Supplement), 5615-5615 , 2026
    2026
  • First-in-class anaplastic lymphoma kinase (ALK)-specific TCR-T cells induce potent and selective antitumor immunity across ALK-driven human cancers
    C Mecca, S Piane, NT Pun, A Azambuja, L Alessandrí, R Blasco, ...
    Cancer Research 86 (7_Supplement), 5619-5619 , 2026
    2026
  • Spatial patterning of the epigenome during vertebrate gastrulation
    AP Azambuja, M Rothstein, TY Kanno, M Simoes-Costa
    Nature Communications , 2025
    2025
    Citations: 1
  • Development of ALK-directed TCR-T cells with potent and specific anti-tumor activity against ALK-positive anaplastic large cell lymphoma
    S Piane, C Mecca, NT Pun, A Azambuja, L Alessandri, PBC Nguyen, ...
    Blood 146, 5909 , 2025
    2025
    Citations: 1
  • A modular enhancer mediates SCRT2 repression of ISLET1 in the spinal cord
    VS Botezelli, TY Kanno, ES Liau, CP Goes, SLC Anticona, AP Azambuja, ...
    Developmental Biology , 2025
    2025
  • MDB-24. Integrated metabolic and epigenetic therapies for Group-3 Medulloblastomas
    D Dang, A Deogharkar, J McKolay, K Smith, P Panwalkar, S Hoffman, S Ji, ...
    Neuro-Oncology Pediatrics 1 (Supplement_1), wuaf001. 223 , 2025
    2025
  • TGF-β signaling controls neural crest developmental plasticity via SMAD2/3
    M Rothstein, AP Azambuja, TY Kanno, C Breen, M Simoes-Costa
    Developmental Cell 60 (12), 1686-1701. e7 , 2025
    2025
    Citations: 11
  • Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis
    D Dang, A Deogharkar, J McKolay, KS Smith, P Panwalkar, S Hoffman, ...
    Cancer Cell 43 (6), 1159-1174. e8 , 2025
    2025
    Citations: 19
  • 438 Development of ALK TCR-T therapy against ALK-positive human cancers
    C Mecca, S Piane, A Azambuja, L Alessandrí, E Bergaggio, ...
    Journal for ImmunoTherapy of Cancer 12 (Suppl 2) , 2024
    2024
  • ASCL1 promotes Scrt2 expression in the neural tube
    CP Goes, VS Botezelli, SM De La Cruz, MC Cruz, AP Azambuja, ...
    Frontiers in Cell and Developmental Biology 12, 1324584 , 2024
    2024
    Citations: 3
  • Discovery of ALK-specific TCR clonotypes for the development of TCR-T cell therapies against ALK-positive cancers
    C Mecca, A Azambuja, L Alessandri, E Bergaggio, S Piane, ...
    Cancer Research 84 (6_Supplement), 21-21 , 2024
    2024
    Citations: 1
  • Pluripotency factors are repurposed to shape the epigenomic landscape of neural crest cells
    AS Hovland, D Bhattacharya, AP Azambuja, D Pramio, J Copeland, ...
    Developmental cell 57 (19), 2257-2272. e5 , 2022
    2022
    Citations: 61
  • The connectome of neural crest enhancers reveals regulatory features of signaling systems
    AP Azambuja, M Simoes-Costa
    Developmental Cell 56 (9), 1268-1282. e6 , 2021
    2021
    Citations: 32
  • A regulatory sub-circuit downstream of Wnt signaling controls developmental transitions in neural crest formation
    AP Azambuja, M Simoes-Costa
    PLoS Genetics 17 (1), e1009296 , 2021
    2021
    Citations: 24
  • Metabolic reprogramming promotes neural crest migration via Yap/Tead signaling
    D Bhattacharya, AP Azambuja, M Simoes-Costa
    Developmental cell 53 (2), 199-211. e6 , 2020
    2020
    Citations: 180
  • Identifying protein-DNA and protein-protein interactions in avian embryos
    AP Azambuja, M Simoes-Costa
    Vertebrate Embryogenesis: Embryological, Cellular, and Genetic Methods, 99-110 , 2019
    2019
    Citations: 1
  • Control of neural crest multipotency by Wnt signaling and the Lin28/ let-7 axis
    D Bhattacharya, M Rothstein, AP Azambuja, M Simoes-Costa
    Elife 7, e40556 , 2018
    2018
    Citations: 69
  • Development of the Coronary System: Perspectives for Cell Therapy From Precursor Differentiation
    AR Moise, ÂMS Costa, M Carvalho, AP Azambuja, J Xavier-Neto, ...
    Endothelium and Cardiovascular Diseases, 11-22 , 2018
    2018
    Citations: 1
  • Cohort profile: the Baependi Heart Study—a family-based, highly admixed cohort study in a rural Brazilian town
    KJ Egan, M Von Schantz, AB Negrão, HC Santos, ARVR Horimoto, ...
    BMJ open 6 (10), e011598 , 2016
    2016
    Citations: 62
  • A population-based study of the stratum corneum moisture
    T de Farias Pires, AP Azambuja, ARVR Horimoto, MS Nakamura, ...
    Clinical, Cosmetic and Investigational Dermatology, 79-87 , 2016
    2016
    Citations: 30

MOST CITED SCHOLAR PUBLICATIONS

  • Metabolic reprogramming promotes neural crest migration via Yap/Tead signaling
    D Bhattacharya, AP Azambuja, M Simoes-Costa
    Developmental cell 53 (2), 199-211. e6 , 2020
    2020
    Citations: 180
  • Control of neural crest multipotency by Wnt signaling and the Lin28/ let-7 axis
    D Bhattacharya, M Rothstein, AP Azambuja, M Simoes-Costa
    Elife 7, e40556 , 2018
    2018
    Citations: 69
  • The search for non‐chordate retinoic acid signaling: lessons from chordates
    MS Simões‐costa, AP Azambuja, J Xavier‐Neto
    Journal of Experimental Zoology Part B: Molecular and Developmental … , 2008
    2008
    Citations: 69
  • Retinoic acid and VEGF delay smooth muscle relative to endothelial differentiation to coordinate inner and outer coronary vessel wall morphogenesis
    AP Azambuja, V Portillo-Sánchez, MV Rodrigues, SV Omae, ...
    Circulation research 107 (2), 204-216 , 2010
    2010
    Citations: 63
  • Cohort profile: the Baependi Heart Study—a family-based, highly admixed cohort study in a rural Brazilian town
    KJ Egan, M Von Schantz, AB Negrão, HC Santos, ARVR Horimoto, ...
    BMJ open 6 (10), e011598 , 2016
    2016
    Citations: 62
  • Pluripotency factors are repurposed to shape the epigenomic landscape of neural crest cells
    AS Hovland, D Bhattacharya, AP Azambuja, D Pramio, J Copeland, ...
    Developmental cell 57 (19), 2257-2272. e5 , 2022
    2022
    Citations: 61
  • Cardiovascular development: towards biomedical applicability: parallel avenues in the evolution of hearts and pumping organs
    J Xavier-Neto, RA Castro, AC Sampaio, AP Azambuja, HA Castillo, ...
    Cellular and molecular life sciences 64 (6), 719-734 , 2007
    2007
    Citations: 58
  • Insights into the organization of dorsal spinal cord pathways from an evolutionarily conserved raldh2 intronic enhancer
    HA Castillo, RM Cravo, AP Azambuja, MS Simões-Costa, S Sura-Trueba, ...
    Development 137 (3), 507-518 , 2010
    2010
    Citations: 33
  • The connectome of neural crest enhancers reveals regulatory features of signaling systems
    AP Azambuja, M Simoes-Costa
    Developmental Cell 56 (9), 1268-1282. e6 , 2021
    2021
    Citations: 32
  • A population-based study of the stratum corneum moisture
    T de Farias Pires, AP Azambuja, ARVR Horimoto, MS Nakamura, ...
    Clinical, Cosmetic and Investigational Dermatology, 79-87 , 2016
    2016
    Citations: 30
  • Evolutionary origins of hearts
    J Xavier-Neto, B Davidson, MS Simoes-Costa, RA Castro, HA Castillo, ...
    Heart development and regeneration, 3-45 , 2010
    2010
    Citations: 26
  • A regulatory sub-circuit downstream of Wnt signaling controls developmental transitions in neural crest formation
    AP Azambuja, M Simoes-Costa
    PLoS Genetics 17 (1), e1009296 , 2021
    2021
    Citations: 24
  • Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis
    D Dang, A Deogharkar, J McKolay, KS Smith, P Panwalkar, S Hoffman, ...
    Cancer Cell 43 (6), 1159-1174. e8 , 2025
    2025
    Citations: 19
  • TGF-β signaling controls neural crest developmental plasticity via SMAD2/3
    M Rothstein, AP Azambuja, TY Kanno, C Breen, M Simoes-Costa
    Developmental Cell 60 (12), 1686-1701. e7 , 2025
    2025
    Citations: 11
  • Repulsive guidance molecules a, b and c are skeletal muscle proteins, and repulsive guidance molecule a promotes cellular hypertrophy and is necessary for myotube fusion
    AF Martins, J Xavier Neto, A Azambuja, ML Sereno, A Figueira, ...
    Cells Tissues Organs 200 (5), 326-338 , 2015
    2015
    Citations: 11
  • Evolutionary origins of hearts. Heart development and regeneration
    J Xavier-Neto, B Davidson, MS Simoes-Costa, RA Castro, HA Castillo, ...
    Academic Press, Elsevier, Amsterdam , 2010
    2010
    Citations: 9
  • ASCL1 promotes Scrt2 expression in the neural tube
    CP Goes, VS Botezelli, SM De La Cruz, MC Cruz, AP Azambuja, ...
    Frontiers in Cell and Developmental Biology 12, 1324584 , 2024
    2024
    Citations: 3
  • Embriogenia cardiovascular
    AC SAMPAIO, AP AZAMBUJA, J XAVIER NETO, MSS COSTA, ...
    Roca , 2013
    2013
    Citations: 3
  • Spatial patterning of the epigenome during vertebrate gastrulation
    AP Azambuja, M Rothstein, TY Kanno, M Simoes-Costa
    Nature Communications , 2025
    2025
    Citations: 1
  • Development of ALK-directed TCR-T cells with potent and specific anti-tumor activity against ALK-positive anaplastic large cell lymphoma
    S Piane, C Mecca, NT Pun, A Azambuja, L Alessandri, PBC Nguyen, ...
    Blood 146, 5909 , 2025
    2025
    Citations: 1