Yang Hu, MD, PhD
Assistant Professor, Shriners Hospitals Pediatric Research Center
Telephone: 215-926-9358 (Internal: 7-9358)
Department of Anatomy and Cell Biology
Shriners Hospitals Pediatric Research Center
Department of Neuroscience
We are interested in axon regeneration and neuroprotection in central nervous system (CNS) after neural injury. Injuries of CNS axons often result in permanent loss of vital functions, such as loss of vision in multiple sclerosis and glaucoma and paralysis in spinal cord injury. This occurs because the axons in the adult mammalian CNS do not regenerate and injury-induced neural cell death. The ultimate goal of my laboratory is to develop efficient therapeutic strategies to achieve neural repair and functional recovery based on the fully understanding of the molecular mechanisms of neurodegeneration and CNS axon regeneration failure.
Previously we showed that the activation of the mTOR pathway by genetically deleting PTEN, can promote axon regeneration in adult retinal ganglion cells (RGCs) using optic nerve injury mouse model. The dramatic down-regulation of mTOR activity in mature neurons after axotomy may partly explain why regeneration is so poor in adult CNS. Our current focus is to extend these initial findings by exploring the mechanistic involvement of the PTEN/mTOR pathway in axon regeneration and functional consequences of regenerating optic nerve fibers after injury.
In addition to stimulate axon regeneration, another key aspect for neural repair is to promote neuronal survival. Our studies indicate that axon injury-induced ER stress plays a critical role in neurodegeneration. We are investigating the mechanisms of ER stress activation and exploring therapeutic means to manipulate signal transduction pathways downstream of ER stress to promote neuronal survival and functional recovery using glaucoma mouse model.
Hu Y, Park KK, Yang L, Wei X, Yang Q, Thielen P, Lee AH, Cartoni R, Glimcher LH, Chen DF and He Z. Differential Effects of Unfolded Protein Response Pathways on Axon Injury-Induced Death of Retinal Ganglion Cells. Neuron. 2012 Volume 73, Issue 3, 9 February 2012, Pages 445-452 (co-corresponding author) Preview, Francesco Roselli, Pico Caroni Life-or-Death Decisions upon Axonal Damage Neuron, Volume 73, Issue 3, 9 February 2012, Pages 405-407
Park KK, Liu K, Hu Y, Kanter JL, He Z. PTEN/mTOR and axon regeneration. Exp Neurol. 2010 Jan 14. (Review).
Park, KK.*, Liu, K.*, Hu, Y.*, Smith, PD.*, Wang, C., Cai, B., Kramvis, I., Sahin, M. and He, Z. Promoting Axon Regeneration in the Adult CNS by Modulating the PTEN/mTOR Pathway. Science 2008 Nov 7;322(5903):963-6. (co-first author)
Hu, Y.1, Park-Min, KH.1, Yarilina, A. and Ivashkiv, LB. Regulation of STAT Pathways and IRF1 During Human Dendritic Cell Maturation by TNFα and PGE2. Journal of Leukocyte Biology 2008 Nov;84(5):1353-60. (co-first author)
Hu, Y, Hu, X, Boumsell, L, Ivashkiv, LB. IFN-gamma and STAT1 arrest monocyte migration and modulate RAC/CDC42 pathways. Journal of Immunology 2008 Jun 15;180(12):8057-65.
Tassiulas I, Park-Min KH, Hu Y, Kellerman L, Mevorach D, Ivashkiv LB. Apoptotic cells inhibit LPS-induced cytokine and chemokine production and IFN responses in macrophages. Hum Immunol. 2007 Mar; 68(3):156-64.
Ge, Z., Hu, Y., Heng, BC, Yang, Z., Ouyang, H., Lee, EH and Cao T. Osteoarthritis and Therapy. Arthritis & Rheumatism 2006 Jun 15;55(3):493-500 (Review).
Hu, Y. and Ivashkiv LB. Costimulation of Chemokine Receptor Signaling by MMP-9 Mediates Enhanced Migration of IFNα-DCs. Journal of Immunology 2006 May 15; 176 (10): 6022-603.
Sharif MN, Tassiulas I, Hu Y., Mecklenbrauker I, Tarakhovsky A, Ivashkiv LB IFN-alpha priming results in a gain of proinflammatory function by IL-10: Implications for systemic lupus erythematosus pathogenesis. Journal of Immunology 2004 May 15; 172(10): 6476-6481.
Hu, Y., Chuang, JZ., Xu, K., McGraw, TG, Sung, CH. SARA, a FYVE domain protein, affects Rab5-mediated endocytosis. Journal of Cell Science 2002 DEC 15, 115 (24): 4755-4763.