BBS Faculty Member - Andrew Lassar

Andrew Lassar

Department of Biological Chemistry and Molecular Pharmacology

Harvard Medical School
Bldg. C, Room 303
240 Longwood Ave.
Boston, MA 02115
Tel: 617-432-3831
Fax: 617-738-0516
Visit my lab page here.

Current work in my lab focuses on the signals and transcription factors that maintain skeletal muscle stem cells, the transcriptional regulatory pathways that regulate chondrocyte formation and maturation, and identification of target proteins to block progression of osteoarthritis.

Skeletal muscle formation and regeneration:
Pax3 and Pax7 are closely related transcription factors that are essential for both skeletal muscle generation in the embryo and the production of skeletal muscle stem cells, termed satellite cells, in the adult. In the context of skeletal muscle stem cells, Pax3 and Pax7 activate the expression of the MyoD family, which are key transcriptional regulators of skeletal muscle development. We are studying the signaling pathways that control the activity of these Pax proteins to induce myogenesis. In addition, we are studying the down-stream transcriptional targets of these proteins (in addition to the MyoD family) to understand how these transcription factors control the genesis of skeletal muscle stem cells.

Chondrogenesis: Most of the bony tissue in vertebrates is initially molded upon a cartilage template which undergoes a stereotypic maturation process where immature chondrocytes undergo maturation, hypertrophy and apopotosis and are replacement by bone tissue; a process termed endochondral ossification. In contrast articular chondrocytes remain immature and do not normally undergo endochondral ossification. We are studying how the initial cartilage template is induced and are trying to elucidate how chondrocytes “decide” whether to undergo maturation, which leads to endochondral ossification, or remain immature, as in the articular cartilage of our joints. The induction of chondrogenesis in the embryo is regionally controlled by the combination of Shh, Wnt, FGF, and BMP signals. We are studying how these signaling molecules regulate the expression of the prochondogenic transcription factor Sox9 by controlling the epigenetic landscape of this locus, how cell shape and the polymerization state of the actin cytoskeleton controls chondrocyte induction and Sox9 gene expression, and the transcriptional circuits that regulate the process of cartilage maturation, endochondral ossification, and maintenance of articular cartilage. In addition, we are both identifying new transcription factors that control chondrocyte maturation and studying how the activity of these transcription factors are regulated by signaling molecules, such as Parathyroid Hormone related Peptide (PTHrP) that regulate chondrocyte maturation during development. Finally, we are trying to determine whether a stem cell population exists for articular cartilage and are trying to elucidate the parameters that control the proliferation and maintenance of articular cartilage.

Identification of targets to block osteoarthritis: A hallmark of both human osteoarthritis and mouse models of this disease, is the induction of signaling pathways that activate the expression of the metalloproteinase, MMP13, in articular chondrocytes themselves. Recent findings in my lab indicate that FoxA transcription factors are both necessary and sufficient for robust expression of MMP13 and other chondrocyte hypertrophy-related genes such as collagen X, VEGF and alkaline phosphatase during cartilage development. Current work focuses on the role of both FoxA factors and chromatin modifying proteins in the progression of osteoarthritis.

Last Update: 8/22/2013


For a complete listing of publications click here.



© 2013 by the President and Fellows of Harvard College