Ramiro Iglesias-Bartolome, Ph.D.

Ramiro Iglesias-Bartolome, Ph.D.
Investigator
NIH Earl Stadtman Investigator
Our lab research focuses on elucidating the signaling mechanisms that control and drive tissue specific stem cell self-renewal and differentiation and their connections to tumor initiation and growth. In particular, our goal is to identify particular G-protein-coupled receptors (GPCRs) and their linked signaling partners that function as master regulators of epithelial stem cells during skin development, tissue homeostasis and malignant transformation.
Areas of Expertise
1. epithelial stem cells 2. signaling 3. GPCRs 4. mTOR 5. squamous and basal cell carcinoma 6. skin

Contact Info

Ramiro Iglesias-Bartolome, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 37, Room 2050
Bethesda, MD 20892
Ph: 240-760-7472
ramiro.iglesias-bartolome@nih.gov
Tissue development and homeostasis depends 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 to 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 their cellular responses. Deregulation of this delicate balance is central to the development of numerous pathologies, including aging-related disorders, decreased tissue regeneration and cancer.

By using a combination of in vitro cell culture systems and animal models we are elucidating these 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  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 the Gαs protein (Gnas) or inactivation of its signaling partner protein kinase A (PKA) are alone sufficient to cause an aberrant expansion of the stem cell compartment, resulting in the rapid formation of basal cell carcinoma (BCC). 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.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Developmental Biology, Molecular Biology and Biochemistry, Stem Cell Biology

Selected Key Publications

  1. Ramiro Iglesias-Bartolome, Akihiko Uchiyama, Alfredo A Molinolo, Loreto Abusleme, Stephen R Brooks, Juan Luis Callejas-Valera, Dean Edwards, Colleen Doci, Marie-Liesse Asselin-Labat, Mark W Onaitis, Niki M Moutsopoulos, J Silvio Gutkind, Maria I Morasso
    Science Translational Medicine. Vol. 10, Issue 451,: 2018. [ Journal Article ]
  2. Iglesias-Bartolome R, Torres D, Marone R, Xiaodong F, Martin D, Chen M, Weinstein LS, Taylor SS, Molinolo AA, and Gutkind JS
    Nat Cell Biol. 17(6): 793-803, 2015. [ Journal Article ]
  3. Iglesias-Bartolome R, Callejas-Valera JL, Gutkind JS
    Curr Opin Cell Biol.. 25(2): 162-169, 2013. [ Journal Article ]
  4. Iglesias-Bartolome R, Patel V, Cotrim A, Leelahavanichkul K, Molinolo AA, Mitchell JB, Gutkind JS
    Cell Stem Cell. 11(3): 401-414, 2012. [ Journal Article ]
  5. Iglesias-Bartolome R, Gutkind JS
    Oncotarget. 3(10): 1061-1063, 2012. [ Journal Article ]
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.
Name Position
Natalia Fernanda Salinas Parra B.S. Postbaccalaureate Fellow
James Hoy Ph.D. Postdoctoral Fellow (CRTA)
Maria Del Pilar Pedro Ph.D. Postdoctoral Fellow (Visiting)
Yao Yuan B.S. Special Volunteer (Graduate Student)