Contact Information
Assistant Professor of Cell and NeurobiologyE-mail: gregor.adams@keck.usc.edu
Office Phone: 323-442-1833
Lab Phone: 323-442-7833
Fax: 323-442-7899
Office Location: 1450 Biggy St- NRT 4507
Lab Location: 1450 Biggy St- NRT 4510
CV: Adams CV.pdf
Education
1995-1999 PhD in Biomedical Sciences Imperial College School of Medicine (St. Mary's Campus), London, U.K. Thesis Title: "The Development of a Haemopoietic Stem Cell Gene Therapy for HIV-1 Infection." 1991-1995 Upper Second Class BSc (Hons) in Molecular Biology University of Edinburgh, Edinburgh, U.K.Recent Publications
Adams, G.B., Martin, R.P., Alley, I.R., Chabner, K.T., Cohen, K. S., Calvi, L.M., Kronenberg, H.M., and Scadden, D.T. (2007). Therapeutic targeting of a stem cell niche. Nat. Biotechnol. 25:238-243. Adams, G.B., Chabner, K.T., Alley, I.R., Olson, D.P., Szczepiorkowski, Z.M., Poznansky, M.C., Kos, C.H., Pollak, M.R., Brown, E.M. and Scadden, D.T. (2006). Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439:599-603. Adams, G.B. and Scadden D.T. (2006). The hematopoietic stem cell in its place. Nat. Immunol. 7:333-337. Johnson, J., Bagley, J., Skaznik-Wikiel, M., Lee, H.-J., Adams, G.B., Niikura, Y., Tschudy, K.S., Tilly, J.C., Cortes, M.L., Forkert, R., Spitzer, T., Iacomini, J., Scadden, D.T. and Tilly, J.L. (2005). Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 122:303-315.
Research Description
In the stem cell niche, neighboring subsets of cells and extracellular substrates house stem cells and provide specialized functions to modulate stem cell self renewal and progeny production in vivo. Therefore, understanding the microenvironmental niche and the intracellular signals that allow for expansion of the stem cells during development or disease settings will assist in the development of hematopoietic stem cell (HSC) based therapies. Currently my research is focused on three important aspects of HSC-niche biology.
Research Projects
1. Identifying the Components of the HSC Niche
Previously we examined the role of the osteoblasts in the bone marrow microenvironment in vivo. Using mice genetically altered with osteoblast specific, activated parathyroid hormone/parathyroid hormone related peptide receptor, we demonstrated that stimulated osteoblastic cells were increased in number, produced high levels of the Notch ligand, Jagged1, and supported an increase in the number of HSCs with evidence of Notch1 activation in stem cells in vivo. However, cells of the osteoblastic lineage are probably only one of the key components of the HSC niche. Currently our research is aimed at examining other components of the HSC niche, as well as identifying the exact location of the HSC niche in vivo. By localizing and identifying the stem cells in the niche, we hope to be able to identify other instructive cues from the microenvironment in terms of the cellular interactions, growth factors or matrix molecules that influence the stem cells.
2. HSC Lodgment at the Endosteal Niche
During both mammalian ontogeny and stem cell transplantation, HSCs in the peripheral circulation will ultimately home to and engraft in the correct microenvironmental niche in the bone marrow. However, the exact mechanism by which the stem cells recognize and lodge in the bone marrow niche is not known. We examined mice engineered to be deficient in the calcium sensing receptor (CaR-/-) and demonstrated primitive cells in the circulation and spleen, but impaired bone marrow localization of HSCs. CaR-/- fetal liver HSCs were normal in number and function, but were defective in establishing effective engraftment, specifically in the bone marrow endosteal niche. These studies demonstrated that an increased concentration of the bone mineral calcium may dictate the specific engraftment of HSCs in the bone marrow endosteal niche. We are continuing to examine this model system as a means to identify the specific mediators of stem cell retention in the niche.
3. HSC Migration to the Niche
While the microenvironment that surrounds stem cells defines the niche, the mechanisms by which the stem cells home to the bone marrow environment is a critical component of understanding basic HSC biology. Previous work by other groups, however, has demonstrated that the mechanisms by which the stem cells migrate to the bone marrow is unclear. Preliminary studies by us suggest that the stem cells may migrate to the bone marrow using previously unrecognized G-protein signaling pathways. Currently our research is focused on the role of this signaling pathway in HSC homing and bone marrow hematopoiesis.Lab Staff
- Dilani Rosa, Lab Manager/Research Technician III
- Xiaoying Zhou, Post-doctoral Research Fellow
- Alan Tseng, Research Technician II
- Narges Rashidi, Graduate Student
- Tigue Tozer, Research Lab Technician
Awarded Grants
Ongoing Research Support
1R21HL084507-01A1 Adams (PI) 06/01/07 - 05/31/09 NIH/NHLBI
Investigating human stem cell - niche interactions.The major goals of this project are to examine the interactions between human hematopoietic stem cells and the bone marrow microenvironment in a murine model of human hematopoiesis. Role: PI
5 U54 HL081030-02 Kronenberg (PI) 09/01/05 - 08/31/10
NIH/NHLBI
Specialized Center for Cell Based Therapy: Stem cell therapy targeting the microenvironment
This project will provide rationale for continued development of a novel, niche-based approach to cell therapies for multiple disease entities. It will create infrastructure needed to rapidly move such therapies from mouse models to pre-clinical assessment to human clinical trial.
Role: Project 3 Leader (Applying stem cell, stem cell niche interactions to clinical use)
Completed Research Support
ASH Fellow Scholar Award Adams (PI) 07/01/02 - 06/30/04 American Society of Hematology Bone Marrow Regulation of Hematopoiesis via the Calcium Sensing Receptor This project will focused on how CaR (calcium sensing receptor) alters two fundamental processes of hematopoiesis: stem cell localization and differentiation in order to provide information for stem cell transplantation. Role: PI
Zelos Therapeutics, Inc Adams (PI) 10/31/04 - 06/30/05
Zelos Therapeutics, Inc
Preclinical evaluation of Ostabolin-CTM
This proposal provided the pre-clinical data to propose a trial of the use of Ostabolin-CTM in the clinical setting.
Role: PI