Philadelphia University + Thomas Jefferson University
Sidney Kimmel Medical College
Department of Medicine

Ramirez, Maria I

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Maria I. Ramirez, PhD

Maria I. Ramirez, PhD

Contact Dr. Ramirez

1020 Locust Street
Jefferson Alumni Hall, Suite 368K
Philadelphia, PA 19107

(215)955-5506
(215)503-5731 fax

Education
Post-doctoral, Parker B. Francis Scholar, 1998-2001
Post-doctoral, Boston University School of Medicine, 1994-1998
Post-doctoral, University of Massachusetts Medical Center, 1992-1994
PhD Chemistry, University of Buenos Aires, Argentina 1985
BA/MS Chemistry, University of Buenos Aires, Argentina 1979

University Appointment
Associate Professor of Medicine

Professional Societies
American Thoracic Society
Society for Developmental Biology

Research and Clinical Interests

We are currently studying novel genetic and epigenetic mechanisms of gene regulation that drive the differentiation of distinct epithelial cell lineages during lung development, and the potential alteration of these mechanisms in lung disease. During embryo development, these mechanisms control the precise spatial and temporal patterns of gene expression that are critical for organogenesis of a functional lung ready for the first breath at birth. In adults, patterns of gene expression also have to be maintained to preserve a healthy lung. Understanding these basic mechanisms in development will in the long term provide the basis to find improvements of fetal lung maturation and to understand altered cell phenotypes in lung disease.

We particularly focus on the regulation of lung epithelial genes by tissue specific transcription factors, non-coding RNAs and chromatin modifications. Although most chromatin modifying protein complexes are ubiquitously expressed, they modify the chromatin within a cell in a timely and gene specific manner. How these complexes acquire specificity to bind to specific regulatory regions in the chromatin is becoming to be elucidated. Recent studies suggest that non-coding RNAs, which comprise more than 90% of the mammalian transcriptome, may provide specificity to chromatin modifying complexes by recruiting them to specific loci to induce or maintain key cellular states such as pluripotency or particular cell lineages. Our goal is to elucidate how these complexes acquire their specificity in lung gene regulation by interacting with long non-coding RNAs (lncRNAs) and the role of this process in lung lineage specification and differentiation.


The functions of most of the lncRNAs identified in the lung are uncharacterized.  Intriguingly, a large number of lncRNAs originate by divergent transcription at promoters of genes encoding transcription factors and developmental genes. Transcription factors that are critical for endoderm and lung epithelial cell differentiation in humans and mice have indeed divergent lncRNA transcripts. We hypothesize that these divergent lncRNAs have essential roles in lung development by regulating epithelial cell differentiation. To study their functions, we are using a unique in vitro system of human induced pluripotent stem cells (iPSCs) that recapitulates the early stages of human or mouse endoderm and lung development. This system allows producing a high number of human cells representing definitive endoderm, lung epithelial progenitors and more mature lung epithelial cells for functional and molecular studies that usually require a high number of cells.

Publications

Most Recent Peer-Reviewed Publications

  1. Epithelial cell-derived secreted and transmembrane 1a signals to activated neutrophils during pneumococcal pneumonia
  2. PKA and CDK5 can phosphorylate specific serines on the intracellular domain of podoplanin (PDPN) to inhibit cell motility
  3. Transcription factor and microRNA interactions in lung cells: An inhibitory link between NK2 homeobox 1, miR-200c and the developmental and oncogenic factors Nfib and Myb
  4. Emergence of a stage-dependent human liver disease signature with directed differentiation of alpha-1 antitrypsin-deficient iPS cells
  5. Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis
  6. Serines in the intracellular tail of podoplanin (PDPN) regulate cell motility
  7. The transcription factors grainyhead-like 2 and NK2-homeobox 1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation
  8. Type I alveolar epithelial cells mount innate immune responses during pneumococcal pneumonia
  9. Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells
  10. Genome-wide analyses of Nkx2-1 binding to transcriptional target genes uncover novel regulatory patterns conserved in lung development and tumors
  11. Epigenetic mechanisms modulate thyroid transcription factor 1-mediated transcription of the surfactant protein B gene
  12. Increased PEA3/E1AF and decreased Net/Elk-3, both ETS proteins, characterize human NSCLC progression and regulate caveolin-1 transcription in Calu-1 and NCI-H23 NSCLC cell lines
  13. Strategic plan for pediatric respiratory diseases research: An NHLBI working group report
  14. Strategic plan for pediatric respiratory diseases research: An NHLBI working group report
  15. Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice
  16. Characterization of the mid-foregut transcriptome identifies genes regulated during lung bud induction
  17. ERM is expressed by alveolar epithelial cells in adult mouse lung and regulates caveolin-1 transcription in mouse lung epithelial cell lines
  18. Angiotensin converting enzyme 2 is primarily epithelial and is developmental regulated in the mouse lung
  19. Key developmental regulators change during hyperoxia-induced injury and recovery in adult mouse lung
  20. Alterations in gene expression in T1α null lung: A model of deficient alveolar sac development