BBS Faculty Member - Yingzi Yang

Yingzi Yang

Department of Developmental Biology


Harvard School of Dental Medicine
REB 512A
188 Longwood Avenue
Boston, MA 02115
Tel: 617-432-8304
Fax: 617-432-3246
Email: yingzi_yang@hsdm.harvard.edu
Visit my lab page here.



My laboratory uses genetic, molecular and cellular approaches to investigate critical roles of cell signaling in embryonic morphogenesis and adult physiology. Because of the essential and pivotal roles played by cell signaling, the focus of my lab is to understand the functions and the underlying molecular mechanisms of Wnt, Hedgehog (Hh) and Hippo (Hpo) signaling, which are key regulators in both embryonic morphogenesis and adult physiology. We take the developing limb and skeleton as our primary experimental systems and have successfully bridged discoveries of fundamental mechanisms with disease characterization and treatment.

We have generated genetic and biochemical tools that have allowed my group to tackle a series of fundamental questions in skeletal and limb development: cell fate determination of chondrocytes versus osteoblasts; induction of the synovial joint; and regulation of sequential chondrocyte proliferation and hypertrophy in the cartilage growth plates. We found that these processes are critically regulated by Wnt/
b-catenin signaling. We also demonstrated the unique functional mechanisms of Wnt5a in regulating planar cell polarity (PCP), which are major findings in non-canonical Wnt signaling. Our work and others’ have revealed that Wnt/b-catenin and Hedgehog signaling abnormalities have a major impact in common skeletal diseases such as osteoporosis and osteoarthritis and now Wnt/b-catenin signaling is a major field of skeletal biology and disease.

In more recent years, benefited from the solid foundations we have built, our research has been extended into several new territories, in particular, translational research of bone diseases. We identified the previously unappreciated significant role of Hh signaling in regulating adult bone mass during aging and found that upregulated Hh signaling in adult chondrocytes may be a risk factor for osteoarthritis. One of our recent major findings is the identification of G
as signaling as a centrally important regulator of Wnt/b-catenin and Hh signaling, breakdown of which causes illustrative human genetic diseases. We have made another more significant finding about the functional mechanisms of the PCP pathway, a fundamentally important and evolutionarily conserved Wnt signaling pathway in providing directional information during morphogenetic and other biological processes. This work has opened a new door to decipher the role and signaling mechanisms of the Wnt/PCP pathway. Because a critical outcome of growth and patterning is organ size control during development and regeneration, we have also tested whether the Hippo signaling pathway plays an evolutionarily conserved role in organ size control and have found that it regulates liver size, tumor formation, stem cell expansion and immune response in mammals.

Our current efforts are divided into four major projects:

1. Understand the role of signaling pathways in cell fate determination. We are investigating the molecular and cellular mechanisms whereby the Gs and Hedgehog signaling pathways regulate fate choices of differentiating mesenchymal progenitor/stem cells under both physiological and pathological conditions.

2. Understand the function of directional information in development and disease. We are investigating the regulatory mechanisms whereby Wnt signaling controls planar cell polarity (PCP) in various aspects of embryonic morphogenesis, skeletal development and homeostasis.

3. Understand the molecular and cellular mechanism underlying mechanotransduction in the skeletal system. The musculoskeletal system generates and is also highly regulated by mechanic forces. We are investigating the roles of the Wnt and Hippo signaling pathways in mediating the effects of mechanotransduction in both development, physiology and regeneration of the skeleton.

4. Understand the molecular and cellular mechanism underlying liver tumor formation caused by chronic liver damage and metabolic abnormalities.



Last Update: 6/28/2017



Publications

Song H, Hu J, Chen W, Elliott G, Andre P, Gao B, and Yang Y (2010). Planar cell polarity breaks the bilateral symmetry by controlling ciliary positioning. Nature 466(7304):378-82.

Gao B, Song H, Elliott G, Garrett L, Bishop K., English M, Andre P, Sood R, Minami Y, Economides AN, and
Yang Y (2011). Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2. Dev Cell 20(2):163-76.

Regard JB, Malhotra D, Gvozdenovic-Jeremic J, Josey M, Chen M, Weinstein LS, Lu J, Shore EM Kaplan FS,
Yang Y (2013). Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification. Nat Med 19(11):1505-12.

Kim W, Khan S, Gvozdenovic-Jeremic J, Kim Y, Dahlman J, Kim H, Park O, Ishitani T, Jho E, Gao B,
Yang Y. Hippo signaling interactions with Wnt/b-catenin  and Notch signaling  repress liver tumorigenesis. J Clin Invest. (2017) 127(1):137-152.



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