Andrew Lassar

Department of Biological Chemistry and Molecular Pharmacology
Harvard Medical School
Bldg. C, Room 303
240 Longwood Avenue
Tel: (617) 432-3831
Fax: (617) 738-0516
Email: andrew_lassar@hms.harvard.edu
Web Page: The Lassar Lab Page
4 postdoctoral fellows

The various projects in my lab seek to elucidate the molecular circuitry that regulates mesodermal cell fate determination during vertebrate development and recruitment of stem cells in the adult.

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 and the transcriptional co-factors that control the activity of these Pax proteins. 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. Lastly, we are studying the signals that regulate satellite cell generation and expansion during skeletal muscle regeneration and growth.

Chondrogenesis: Most of the bony tissue in vertebrates is initially molded upon a cartilage template which undergoes a stereotypic maturation process and replacement by bone tissue; a process termed endochondral ossification. We are studying how the initial cartilage template is induced and modeled. We have found that Hedgehog signaling induces a competence in paraxial mesodermal precursor cells (termed somites) for subsequent BMP signals to activate chondrogenesis, and that this chondrogenic competence is mediated by the induction of both Sox9 and Nkx3.2, two pro-chondrogenic transcription factors. We are studying how Sox9 and Nkx3.2 regulate the induction of chondrogenesis, how cell shape and the polymerization state of the actin cytoskeleton control chondrocyte differentiation, and how Sox9 and Nkx3.2 work with Runx family transcription factors and various signaling molecules to regulate the process of cartilage maturation, endochondral ossification, and maintenance of articular cartilage. In addition, we are studying how the activity of these transcription factors that play a crucial role in chondrocyte maturation are regulated by signaling molecules, such as Parathyroid Hormone related Peptide (PTHrP) that regulate chondrocyte maturation during development. Future work will focus on evaluating whether the activity of these transcription factors is altered in experimental models of osteoarthritis. 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.

References:

Tzahor E, Kempf H, Mootoosamy RC, Poon AC, Abzhanov A, Tabin CJ, Dietrich S, and Lassar AB. (2003). Antagonists of Wnt and BMP signaling promote the formation of vertebrate head muscle. Genes Dev. Dec 15;17(24):3087-3099.
Tamara Holowacz, Li Zeng, Andrew B. Lassar (2006). Asymmetric localization of Numb in the chick somite and the influence of myogenic signals. Developmental Dynamics. 633-45.
Sylvain Provot, Hervé Kempf, L. Charles Murtaugh, Ung-il Chung, Dae-Won Kim, Jay Chyung, Henry M. Kronenberg and Andrew B. Lassar (2006). Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation. Development. 133, 651-662.
Hervé Kempf, Andreia Ionescu, Aaron M. Udager, and Andrew B. Lassar (2007). Prochondrogenic signals induce a competence for Runx2 to activate hypertrophic chondrocyte gene expression. Developmental Dynamics. In press