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Associate Professor, Endocrinology

Education and Employment:

1994 PhD  Medical Biochemistry, Medical School, University of the Witwatersrand, Johannesburg, South Africa

1994-1997  Postdoctoral Fellow, Section on Genomic Structure and Function.  Laboratory of Molecular and Cellular Biology, NIDDK, National Institues of Helath, Bethesda, MD

1998-1999  National Research Service Award Postdoctoral Fellow.  Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO

2000-2002  Research Instructor in Medicine.  Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO

2003-present.  Assistant Professor of Medicine.  Associate Director of the Bone Laboratory.  Division of Endocrinology and Metabolism, Emory University School of Medicine.

2009-present. Research Biologist.  Department of Veterans Affairs, Atlanta VA Medical Center 

The integrity of the skeleton is maintained by the periodic removal of old bone and its replacement with new bone. This bone renewal process is referred to as “remodeling” and is regulated by osteoclasts, cells that break down bone, and by osteoblasts cells that build new bone.  In bone diseases leading to osteoporosis, remodeling becomes unbalanced and the rate of bone breakdown exceeds the rate of new bone formation leading to a progressive loss of bone mass. The formation of osteoclasts, the cells responsible for breaking down bone, is regulated principally by two critical factors, the cytokine Receptor activator of NF-kappaB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG). While RANKL stimulates osteoclast formation, OPG inhibits it. Consequently osteoclast formation (and the rate of bone breakdown) is regulated principally by the amount of RANKL in the bone marrow relative to the concentration of OPG. Any decrease in OPG, will lead to a relative increase in the concentration of RANKL thus favoring bone loss. 

My laboratory has 3 main research focuses:

1) The immuno-skeletal interface.  In recent years the tight integration between skeletal and immune systems has begun to be appreciated. Almost a decade ago we discovered anti-osteoclastogenic activities in B cell conditioned media. Following the identification of OPG, as a key regulator of osteoclastogenesis, and with the recent development of B cell KO mice, we have been able to ratify a potent suppressive effect of B cells on bone resorption in mice, as a consequence of OPG production. In fact our data suggest that B cells are the dominant source of OPG in the bone microenvironment and that T cell to B cell interactions, associated with normal immunological processes, regulate B cell OPG production and hence bone homeostasis. We are currently investigating how immune-dysfunction associated with a myriad of disease processes and the immunosuppressive agents utilized to manage inflammatory and immunologically-related diseases, may impact skeletal remodeling in animal models. 

2) Nanotechnology: Nanotechnology is a multidisciplinary field involving the development of engineered macromolecules at the nanometer size (typically 1-100 nm). Recent advances in nanotechnology have raised exciting possibilities for the application of nanomaterials to biomedical imaging and the targeted delivery of drugs. Silica based nanoparticles appear to have good biocompatibility as they are generally thought to be non-toxic in vivo, and consequently are good candidates for use in biomedical applications. We have recently identified a novel silica-based nanoparticle formulation that has potent stimulatory effects on the formation of osteoblasts, and concomitant inhibitory effects on the formation of osteoclasts. These nanoparticles represent a potentially powerful dual anticatabolic and proanabolic agent for the treatment of numerous skeletal diseases such as osteoporosis. 

3) Modulation of NF-kappaB as an anabolic strategy for maximizing peak bone mass: The NF-kappaB signal transduction pathway is well established to be critical for osteoclast formation and activity and suppression of NF-kappaB activation is established to prevent osteoclastogenesis and bone resorption in vitro and in vivo. 

We recently reported that NF-kappaB is also a potent inhibitor of in vitro osteoblast differentiation and that pharmacological suppression of NF-kappaB activation potently induces osteoblast differentiation and mineralization in vitro. Our recent studies suggest that multiple pharmacological agents and food supplements associated with anabolic actions in vivo, may achieve their activities through suppression of NF-kappaB.

Link to Publications: http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=PureSearch&db=pubmed&term=%28Weitzmann%20MN%5BAuthor%20Name%5D%29