Lanske Laboratory

The Lanske Lab researches the endocrine regulation of mineral ion homeostasis and skeletogenesis. In vivo research requires the use of a wide variety of animal models and molecular biology techniques to answer complex questions.  In the Lanske Lab several knockout mice were generated and are currently being used, often in combination with each other and with mice from collaborating groups.  The use of transgenic mouse lines harboring the CRE-LoxP system to alter gene expression in specific tissues at specific ages is part of the in vivo investigations.  New innovative animal models are being established, such as retroviral mouse lines to study the interaction of genes in specific tissues.  In addition to mice, in vitro analyses using various cell lines and primary cell and organ cultures are being performed in the lab. For specific questions, chick embryos are used to study developmental aspects of the genes as well. 

A key focus of the Lanske Lab has been, and continues to be, FGF-23, a circulating phosphaturic factor produced in osteoblasts, osteocytes, cementoblasts, and odontoblasts. FGF-23 inhibits renal phosphate reabsorption and vitamin D synthesis, thus playing a key role in phosphate homeostasis.  Mutations in FGF-23 and genes that regulate its expression and activation have been linked to several disease processes, including autosomal dominant hypophosphatemic rickets (ADHR), oncogenic osteomalacia (OOM) and X-linked hypophosphatemia (XLH), autosomal recessive hypophosphatemia with hyperphosphaturia (ARHR). Research in the Lanske Lab has provided important data regarding FGF-23, its relationship to other mineral homeostasis regulators such as PTH (parathyroid hormone), Klotho and vitamin D and how it functions in these disease processes.  FGF-23 was also found to affect bone mineralization independent of its role in systemic phosphate homeostasis, adding significant new data regarding FGF-23’s physiological properties.  The work in the lab continues to explore the complex interactions of FGF-23, PTH, vitamin D and other molecules using a new innovative mouse model for which Dr. Lanske received one of the few Challenge Grants from the National Institutes of Health. 

More recently the Lanske Lab has expanded its research to investigate the role of Klotho during chronic kidney disease (CKD). Special emphasis is given to explore the possible role and source of Klotho in the development of metabolic bone disease (MBD - renal osteodystrophy). Furthermore, sophisticated in vivo techniques are being applied to identify the responsible genes and/or signaling pathways involved in the development of parathyroid gland hyperplasia during various diseases.

The Lanske Lab is also investigating how Indian hedgehog (Ihh), PTH-related protein (PTHrP) and other factors regulate the growth and maintenance of skeleton. These processes are controlled by a complex network of genes, and unraveling this network is critical to understanding and developing clinical responses for developmental defects, disease processes and skeletal regeneration. The work on Ihh has revealed crucial information on the roles of this and other key genes in the core regulatory mechanism of the development and maintenance of the growth plate and subsequently endochondral bone formation.  Recent experiments have identified additional factors in this regulatory network which are now being included in the investigations.

Laboratory Personnel

Visiting assistant professor
Komaba Hirotaka,  MD PhD

Collaborator BIDMC
Junichi Hanai, MD

Postdoctoral research fellows
Tadatoshi Sato, PhD
Katsuhiko Amano, DDS, PhD
Noriko Ide, MD, PhD
Jovana Kaludjerovic, PhD
Rui Ye

Research associate
Michael Densmore, MA

Graduate student
Yi Fan, DMD
Elmisalati Waeil H, MMSc

Research assistant
Hao Wang