Dr. Ross A. Tubo
Distinguished Alumni Seminar Series
September 25th, 2008

Ross Tubo, Ph.D.
Vice-President, Stem Cell and Chemokine Biology
Genzyme Corporation

49 New York Avenue
Framingham, MA 01701
508-872-9080 FAX

The research in my laboratory is focused on mobilization of bone marrow derived stem cells and the cellular mechanisms involved in cellular recruitment, migration to sites of injury and/or inflammation, and return to homeostasis following repair.

Hematopoietic (HSC) and mesenchymal (MSC) stem cells represent two distinct type of stem cell within the bone marrow. The HSC is the cell responsible for the reconstitution of immune and hematologic systems following bone marrow transplantation. HSC are maintained within the bone marrow by MSC which form a nurturing niche. MSC produce cytokines and chemokines in response to local and systemic signals, causing migration into and out of the niche.

MSC are also present in other tissues and can be activated by tissue injury to produce the chemokine, Stromal Derived Factor-1 (SDF-1, aka CXCL12). Hematopoietic-derived inflammatory cells expressing the receptor for SDF-1 (CXCR4) can migrate to these activated sites. We are in the process of studying the control mechanisms involved in the dynamic migration of repair cells following tissue injury and return to homeostasis.

Mobilization of HSC

HSC can be mobilized from the bone marrow niche using an antagonist of CXCR4, known as plerixafor. Plerixafor was recently approved by the FDA for mobilization of HSC for autologous transplant. We are in the process of studying other methods for mobilizing HSC from bone marrow.

Stem Cell and Chemokine Biology

Mesenchymal Stem Cells have been shown to “activate” in response to local tissue injury and hypoxia, producing chemokine and cytokine signals, resulting in inflammatory and repair cell recruitment. We are in the process of studying the role of CXCR4 antagonists in acute and chronic settings.

We are also studying the mechanisms by which MSC modulate the immune response in tissue injury and inflammation. We have be able to observe interesting patterns of chemokine and chemokine receptor expression.

SDF-1 / CXCR4 has been shown to play a role in…
• Normal HSC trafficking
• Hematologic and solid tumor cancer and metastasis
• Recruitment of cells to sites of tissue injury
        – Tissue injury, hypoxia, inflammation, and repair
        – Tissue Fibrosis
• Autoimmune Diseases, including but not limited to…
        – Diabetes
        – Multiple sclerosis
        – Rheumatoid arthritis
        – Thyroid autoimmunity