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Research Interests

The Insogna research program has three components: translational, clinical, and analytical clinical research.

Translational Research

Translational research in the Insogna lab is largely wet bench work, centered on cellular and molecular mechanisms of bone remodeling. The lab has had a long-standing interest in the role of cytokines in mediating both the anabolic and catabolic actions of PTH in bone. This work includes studies on the role of Colony Stimulating Factor 1 in mediating PTH-induced resorption. Exploring the effect in bone of the major CSF1 isoforms and clarifying the intracellular mediators of CSF1’s effects on mature osteoclasts are two examples of ongoing projects related to this growth factor. Another area of investigative interest is the role of dietary protein in regulating mineral homeostasis and the mechanisms by which amino acids regulate paracellular calcium transport and iron metabolism.

Two new areas or research in the lab are dysregulated osteoclastogenesis in myeloma and the role of the hypothalamus in regulating bone metabolism.

Karl Insogna directs the Yale Core Center for Musculoskeletal Disorders, a P30 Core Center funded by NIAMS, which supports the development and analysis of animal models of musculoskeletal disorders.

Clinical Research

The Insogna group’s clinical research interests include rare syndromes of high and low bone density and the inherited syndromes of osteoporosis and hypercalciuria. In 2002 the Insogna lab, together with the Richard P. Lifton lab, described a patient with high bone density who proved to have a gain-of-function mutation in LRP5. This led to an explosion of interest in Wnt signaling in bone, which remains an area of clinical interest. Another major focus has been studying the pathogenesis of X-linked hypophosphatemic rickets and developing new treatments for this disorder.

Analytical Clinical Research

The Insogna group manages an analytical clinical laboratory that provides regional and whole-body densitometric analyses by DXA and measurements of PTH, vitamin D metabolites, bone turnover markers and a panel of bone-active cytokines such as RANKL/RANK, OPG, CSF1, IGF1, IL-6, IL-1 and TNF-α.