Ramiro Iglesias-Bartolome, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 37, Room 2050
- Bethesda, MD 20892
- 240-760-7472
- ramiro.iglesias-bartolome@nih.gov
RESEARCH SUMMARY
Our laboratory studies the signal and transcriptional networks regulating epithelial proliferation and differentiation, primarily using skin as a model system. The skin epidermis is functionally divided into compartments maintained by stem and transit-amplifying progenitor cells. Environmental assaults and genomic abnormalities can result in the imbalance of the homeostatic functions of epithelial cells, leading to uncontrolled cell proliferation or elimination of tissue-regenerative cells by death, differentiation, or senescence. Understanding the pathways regulating these cell fates can provide essential insights into cancer initiation and a host of pathologies involving progressive loss of tissue-specific regenerating cells.
Areas of Expertise
Ramiro Iglesias-Bartolome, Ph.D.
Research
Tissue development and homeostasis depend on the activity of specific stem cell populations. In particular, the epidermis of the skin and oral mucosa is highly dependent on resident self-renewing stem cells due to its continuous need to replace cells lost by desquamation or repair wounds. This makes the epidermis a unique system to study stem cell biology. The proper balance between self-renewal and differentiation in epithelial stem cells is largely achieved by a milieu of micro-environmental signals controlling stem cell fate decisions and cellular responses. Deregulation of this delicate balance is central to the development of numerous pathologies, including aging-related disorders, decreased tissue regeneration, and cancer.
Using a combination of in vitro cell culture systems and animal models, we elucidate the signaling mechanisms that control and drive epithelial stem cell self-renewal and differentiation. Our focus at this moment is on G-protein-coupled receptors (GPCRs) and their signaling partners. GPCRs are the largest family of cell-surface molecules involved in signal transduction, playing central roles in numerous physiological processes and pathological conditions along with their associated G proteins. Since GPCRs are the direct or indirect target of more than 25% of therapeutic drugs on the market, they represent a unique potential target for the pharmacological intervention of stem cell activity.
Most GPCRs relay their signal by coupling to heterotrimeric Gα, β, and γ subunits. Gα proteins are classified into four different families: Gαs, Gαi/o, Gαq/11 and Gα12/13. We have recently demonstrated that among Gα proteins, Gαs plays a central role in coordinating self-renewal and differentiation in epithelial stem cells. In mice, conditional epidermal deletion of the gene coding for Gαs protein or inactivation of its signaling partner protein kinase A (PKA) is sufficient to cause an aberrant expansion of the stem cell compartment, resulting in basal cell carcinoma (BCC) formation. These findings reveal that Gαs-PKA function as part of a tumor-suppressive axis, limiting the proliferation of epithelial stem cells and maintaining hair follicle and skin homeostasis. Furthermore, they indicate that GPCRs may be involved in differentiation and tumorigenicity within the epidermal stem cell compartment.
Our major goal is to identify particular GPCRs and their linked signaling partners that function as master regulators of epithelial stem cells during skin development and tissue homeostasis and their connection to malignant transformation and cancer. Our approaches include a variety of animal models and primary cell culture systems, synthetic biology methods, gene expression profiling by RNA sequencing, high-throughput screenings, microscopy, and biochemical assays.
Publications
- Bibliography Link
- View Dr. Iglesias-Bartolome's Complete Bibliography at NCBI.
Activation of G-Protein Coupled Receptor–Gαi Signaling Increases Keratinocyte Proliferation and Reduces Differentiation, Leading to Epidermal Hyperplasia
Transcriptional signature primes human oral mucosa for rapid wound healing
Biography
Ramiro Iglesias-Bartolome, Ph.D.
Ramiro Iglesias-Bartolome obtained his degree in Biology at the National University of Cordoba, Argentina. He then joined the laboratory of Dr. Jose L. Daniotti at the same University, where he obtained his Ph.D in 2008. In 2009 he joined NIDCR at the NIH for his post-doctoral training in the group of Dr. J. Silvio Gutkind. In 2015 he joined the Developmental Skin Biology Section, NIAMS-NIH, as a research fellow in the group of Dr. Maria I. Morasso. In 2016 he joined the Laboratory of Cellular and Molecular Biology, NCI, as a Stadtman Tenure-Track Investigator.
Job Vacancies
We have no open positions in our group at this time, please check back later.
To see all available positions at CCR, take a look at our Careers page. You can also subscribe to receive CCR's latest job and training opportunities in your inbox.
Team
News
Learn more about CCR research advances, new discoveries and more
on our news section.