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Cellular & Molecular Biology

Eben Alsberg, PhD, Associate Professor

Research Interests:

Biomimetic tissue engineering; innovative biomaterials and drug delivery vehicles for functional tissue regeneration and cancer therapy; control of stem cell differentiation; mechanotransduction and the influence of mechanics on cell and tissue function; cell-cell interactions.

Dr. Alsberg’s laboratory focuses on engineering functional biologic replacements to repair damaged or diseased tissues in the body. We use the complex signals that are implicated in tissue morphogenesis, repair, and homeostasis as a template for the development of innovative biomaterials for tissue regeneration.

Through the precise temporal and spatial presentation of soluble bioactive factors, mechanical forces, and biomaterial physical and biochemical properties, we aspire to create microenvironments that regulate cell gene expression and new tissue formation.

Some areas of active investigation include controlling stem cell differentiation, delivering bioactive factors sequentially, developing spatially patterned constructs, understanding cell-cell interactions, and determining mechanical influences on cell function.

Email: eben.alsberg@case.edu

Edward M. Greenfield, PhD, Professor and Director of Research

Research Interests:

The underlying principle of Dr. Greenfield’s research is to study the cellular and molecular mechanisms that regulate clinically important aspects of bone biology. The long-term goal is to understand these processes in sufficient detail to help develop novel diagnostics and therapeutics. With this goal in mind, Dr. Greenfield have three active areas of research:

  1. Osseointegration and aseptic loosening of orthopaedic implants. These studies focus on determining whether bacteria impair osseointegration and whether bacteria contribute to aseptic loosening. Dr. Greenfield also conducts studies to develop counter-measures for impaired osseointegration.
  2. The balance between the catabolic and anabolic effects of parathyroid hormone. These studies focus on the regulation by Protein Kinase Inhibitor gamma of intracellular signaling pathways induced by parathyroid hormone.
  3. Tumorigenesis and metastasis in osteosarcoma. These studies focus on the roles of tyrosine kinases and miRNAs.

Shunichi Murakami, MD, PhD, Assistant Professor

Research Interests:

Molecular genetics of bone and cartilage. Signaling pathways that regulate chondrocyte and osteoblast differentiation.

Dr. Murakami’s laboratory focuses on the role of fibroblast growth factor (FGF) and mitogen-activated protein kinase (MAPK) signaling in mesenchymal cells. During embryonic development, FGFR2 is expressed in the perichondrium and periosteum in the long bones, mesenchymal cells in the cranial sutures, and osteoblasts.

Activating mutations in FGFR2 cause skeletal syndromes characterized by craniosynostosis. These include Apert and Crouzon syndromes. In contrast, FGFR3 is expressed in proliferating and prehypertrophic chondrocytes in the growth plates.

Activating mutations in FGFR3 cause the most common forms of human dwarfism, achondroplasia and thanatophoric dysplasias, indicating FGFR3 is a negative regulator of bone growth. We hypothesize that the MAPK pathway plays an important role in FGFR2 and FGFR3 signaling during skeletal development.

Dr. Murakami uses genetically engineered mice to identify the role of MAPK and FGFR in skeletal development. His recent genetic experiments strongly suggested that Fgfr3 signaling inhibits bone growth by inhibiting hypertrophic chondrocyte differentiation through the MAPK pathway.

Recent experiments also indicated that Fgfr3 and the MAPK pathway control the timing of growth plate closure. Dr. Murakami’s current research focuses on the mechanisms whereby Fgfr3 and the MAPK pathway control chondrocyte differentiation and closure of the growth plates.

Email: shun@case.edu

Guang Zhou, PhD, Assistant Professor

Research Interests:

Transcriptional control of bone and cartilage formation.

Dr. Zhou’s laboratory focuses on studying how transcription factors interact with each other to determine cell fate and regulate cell function during skeletogenesis and bone metastasis.

Utilizing molecular, biochemical and genetic approaches, Dr. Zhou has shown that chondrogenic transcription factor SOX9 is a strong inhibitor for osteogenic transcription factor RUNX2 during bone formation. His laboratory is currently studying the role of SOX9 during chondrocyte hypertrophy using transgenic mice models.

Other projects include studying the roles of transcription co-factor Ctbp and tumor suppressor gene Rb in chondrocyte and osteoblast differentiation using transgenic and knockout mice models. His work will provide a better understanding of how tissue-specific and ubiquitous transcription factors interact with each other to control bone and cartilage formation.Eventually it could lead to the development of therapeutic and diagnostic methods for bone diseases.

Email: guang.zhou@case.edu