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College of Veterinary Medicine

Jianzhong Yu

Yu

Assistant Professor

PhD, Martin-Luther-University Halle-Wittenberg, Germany
Postdoc, Florida State University
           Johns Hopkins University School of Medicine

207 Coles Hall
Phone: (785)532-4507
Email: Jianzhongyu@ksu.edu
Google Scholar: https://scholar.google.com/citations?user=_fVs16oAAAAJ&hl=en

Research Interests

The work in my lab focuses on the basic research of cancer biology, with the aim of understanding the molecular mechanisms of organ size control and tumorigenesis. Currently, there are two research directions in my lab. The first research direction focuses on the molecular mechanisms underlying upstream regulation of the Hippo signaling pathway. The research second direction focuses on how tissue growth is regulated in response to nutrient stress.

1) Molecular mechanisms underlying upstream regulation of the Hippo signaling pathway. The Hippo signaling pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. While the regulation of the core Hippo pathway is well studied, the upstream regulation of this pathway is less defined. Recent studies have identified several proteins implicated as upstream regulators of the Hippo pathway. A unique feature of these upstream regulators is that their overgrowth phenotypes are relatively mild compared to those of the core components. In addition, distinct phenotypes were observed for these regulators. The mild and distinct phenotypes of the identified upstream regulators indicate that the Hippo signaling pathway is regulated by diverse upstream signals. Despite these advances, an outstanding question in the field is how the divergent upstream signals are coordinated to activate the core Hippo pathway. My previous work identified Kibra-Expanded-Merlin (KEM) protein complex as a key regulatory machinery upstream of the Hippo pathway. My lab recently identified a novel upstream regulator of the Hippo pathway that plays a role in cytoskeleton remodeling. Having these upstream regulators as entry points, my lab will continue to identify additional regulators/signals that function upstream of the Hippo signaling pathway. This goal will serve as a foundation for the investigation of the molecular mechanisms underlying upstream regulation of the Hippo signaling pathway.

2)Novel regulation of tissue growth in response to nutrient stress. Nutrient restriction (NR) without malnutrition is the most robust environmental intervention that is known to slow a number of diseases (including cancer) in a variety of species. Indeed, NR has been shown to delay the incidence and suppress the growth of various types of tumors. The protective effects of NR on tumor incidence and growth were first reported in the early 1900s and have since been observed in numerous epidemiological studies and laboratory rodent and non-human models. To date, the anti-tumorigenic effects of NR have been well established and its potential implications in both cancer prevention and treatment have been suggested. Despite these advances, our understanding of the molecular mechanisms underlying the anti-tumorigenic effects of NR remain fragmented. My lab recently identified Headcase (Hdc) and Unkempt (Unk) as two NR-specific tumor suppressors. By elucidating how Hdc and Unk activities are regulated by nutrient stress and further, how this regulation determines the sensitive of cells to NR and subsequent NR resistance effects, our work will provide new insights into the molecular mechanisms underlying NR resistance response during animal development, and to have a transformative impact on understanding the development of NR resistance related human diseases.

Awards and Grants

2020-2025               R01 research grant, NIH/NIGMS
2018-2020               Developmental Research Project Award, Kansas INBRE
2017, 2018, 2019    Innovative Research Awards, Johnson Cancer Research Center, KSU
2017, 2018              Success for Young Investigators Awards, KSU
2016-2017               Equipment Award, Johnson Cancer Research Center, KSU
2011-2013               Young Investigator Award, The Children’s Tumor Foundation (CTF)

Selected Publications:

  1. Naren Li, Qinfang Liu, Yulan Xiong*, Jianzhong Yu* (2019). Headcase and Unkempt regulate tissue growth and cell cycle progression in response to nutrient restriction. Cell Reports(in press; *corresponding author).
  2. Yu J, Pan D (2018). Validating upstream regulators of Yorkie activity in Hippo signaling through scalloped-based genetic epistasis. Development 145(4): dev157545.
  3. Ge M, Hong Liu H, Zhang Y, Li N, Zhao S, Zhao W, Zhen Y, Yu J, He H, Shao R (2017). The anti-hepatic fibrosis effects of dihydrotanshinone I are mediated by disrupting the yes-associated protein and transcriptional enhancer factor D2 complexand stimulating autophagy. British Journal of Pharmacology 174(10):1147-1160.
  4. Chan P, Han X, Zheng B, DeRan M, Yu J, Jarugumilli GK, Deng H, Pan D, Luo X, Wu X (2016). Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway. Nat Chem Biol. 12(4):282-9 
  5. Liu B, Zheng Y, Yin F, Yu J, Silverman N, Pan D (2016). Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila. Cell 164(3):406-19.
  6. Deng H, Wang W, Yu J, Zheng Y, Qing Y, Pan D (2015). Spectrin regulates Hippo signaling by modulating cortical actomyosin activity. Elife 31: 4. doi: 10.7554/eLife.06567.
  7. Yin F, Yu J, Zheng Y, Chen Q, Zhang N, Pan D (2013). Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell 154(6):1342-55.
  8. Ni L, Li S, Yu J, Min J, Brautigam CA, Tomchick DR, Pan D, Luo X (2013). Structural basis for autoactivation of human Mst2 kinase and its regulation by RASSF5. Structure 21(10):1757-68.
  9. Koontz LM, Liu-Chittenden Y, Yin F, Zheng Y, Yu J, Huang B, Chen Q, Wu S, Pan D (2013). The Hippo effector Yorkie controls normal tissue growth by antagonizing scalloped-mediated default repression. Developmental Cell 25(4):388-401.
  10. Ling C, Zheng Y, Yin F, Yu J, Huang J, Hong Y, Wu S, Pan D (2010). The apical transmembrane protein Crumbs functions as a tumor suppressor that regulates Hippo signaling by binding to Expanded. Proc. Natl. Acad. Sci. USA, 107(23):10532-7
  11. Tian W, Yu J, Tomchick D, Pan D, Luo X(2010). Structural and Functional Analysis of the YAP-binding Domain of Human TEAD2.  Proc. Natl. Acad. Sci. USA, 107(16):7293-8
  12. Yu J, Zheng Y, Dong J, Klusza S, Deng WM, Pan D (2010). Kibra functions as a tumor suppressor protein that regulates hippo signaling in conjunction with Merlin and expanded. Developmental Cell 18(2):288-99.
  13. Alarcón C, Zaromytidou AI, Xi Q, Gao S, Yu J, Fujisawa S, Barlas A, Miller AN, Manova-Todorova K, Macias MJ, Sapkota G, Pan D, Massagué J (2009).  Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell 139(4):757-69.
  14. Yu J, Poulton J, Huang YC, Deng WM (2008). The Hippo Pathway Promotes Notch Signaling in Regulation of Cell Differentiation, Proliferation, and Oocyte Polarity. PLoS ONE. 3(3): e1761.

Motivated undergraduate students, graduate students and postdoc candidates are welcome to contact Dr. Yu for open positions.