1. Project 3: Environmental PPARγ Agonist-Mediated Toxicity in the Developing Immune System Jennifer Schlezinger Environmental Health Boston University Superfund Research Program

2. Kawai M et al. 2010. Am J Physiol Endocrinol Metab PPARγ Is a Key Transcription Factor in Bone PPAR  RXR HSC WBCs RBCs

3. Takada et al. 2009. Nat. Rev. Rheumatol. Rzonca et al. 2004. Endocrinology Aging also is associated with a reduced capacity to generate B cells! Osteoporosis: Obesity of the bone.

4. Long Term Goal: Determine molecular mechanisms by which Superfund chemicals (individually and as mixtures) impair ongoing development in the immune system. Current Objective: Determine the role of PPARγ (and other nuclear receptors) in phthalate- and organotin- induced alterations in bone marrow physiology. Hypothesis: Environmental PPAR/RXR ligands suppress B lymphopoiesis by two mechanisms: 1)directly, by inducing apoptosis in early B cells 2)indirectly, by altering the bone marrow microenvironment that supports lymphopoiesis, resulting in aging-like suppression of immune responses. Specific Aims: 1.Determine the relationship between PPAR and RXR activation and the functional consequences for MSC differentiation. In vitro. 2.Determine the mechanisms by which environmental PPAR/RXR agonists damage B lymphopoiesis, both directly and indirectly. In vitro. 3.Determine mechanisms by which in vivo exposure to PPAR/RXR agonists negatively affects bone physiology, lymphopoiesis and immune responses. In vivo.

5. In press: Pillai H, Fang M, Beglov D, Kozakov D, Vajda S, Stapleton H, Webster T, Schlezinger J. 2014. The flame retardant Firemaster 550 contains PPARγ ligands that induce adipogenesis and suppress osteogenesis. Environ. Health Perspect. *Inter- and intra-SRP collaboration. *Core collaboration. *Trainee. Aim 1 Bragdon B, Burns R, Baker AH, Belkina AC, Morgan EF, Denis GV, Gerstenfeld LC and Schlezinger JJ. 2014. Intrinsic sex-linked variations in osteogenic and adipogenic differentiation potential of bone marrow multipotent stromal cells. J. Cell. Physiol. *Trainee. Aim 1 Project 3: Publications

6. What’s happening this summer? 1. Finishing 16 months of making fat mice… Imaging VhTBT

8. What’s happening this summer? 3. Training – Lariah Extending adipogenesis/ osteogenesis studies to parabens. Working with Nrf2 and Wnt signaling.