Fenghua Hu
Assistant Professor
Fenghua Hu

Phone

607-255-0667

Address

Department of Molecular Biology & Genetics
345 Weill Hall
Cornell University
Ithaca, NY 14853

Email

Web Sites

Department Profile
Lab Website

Background

Fenghua Hu is an Assistant Professor in the Department of Molecular Biology and Genetics and is a member of the Weill Institute for Cell and Molecular Biology (Weill Institute). She received her B.S. in Biochemistry from Peking University in China in 1997 and her Ph.D. from Baylor College of Medicine in 2002. She received her postdoctoral training at Yale University and joined Cornell as a faculty member in 2008.

Research Description

My lab is interested in the molecular mechanisms of Frontotemporal Lobar Degeneration with ubiquitin and TDP-43 positive inclusions (FTLD-U), a very common early onset dementia disease often associated with Amyotrophic Lateral Sclerosis (ALS). Mutations in Progranulin (PGRN), resulting in PGRN haplo-insufficiency, are one of the main causes of FTLD-TDP. A transmembrane protein of unknown function, TMEM106B, is a risk factor for FTLD-TDP with PGRN mutations. More recently, mutations in C9orf72, a gene of unknown function, were found to the main cause of mixed ALS/FTLD phenotypes. We are trying to understand the cellular functions of PGRN, TMEM106B and C9orf72 as well as other genes implicated in FTLD/ALS. We hope our studies will not only shed light on the molecular and cellular mechanisms of FTLD but also on the regulation of normal cellular functions by these FTLD proteins, such as regulation of autophagy-lysosome functions by PGRN, TMEM106B and C9orf72.

Selected Publications

Sullivan PM, Zhou X, Robins AM, Paushter DH, Kim D, Smolka MB, Hu F. The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway. Acta Neuropathologica Communications. 2016 May 18:4(51).

Zhou X, Sun L, Oliveira F, Qi X, Brown WJ, Smolka M, Sun Y, Hu F. Prosaposin facilitates sortilin independent lysosomal targeting of progranulin. J Cell Biol. 2015 Sep 14;210(6):991-1002.

Hsu F, Hu F, Mao Y. Spatiotemporal control of phosphatidylinositol 4-phosphate by Sac2 regulates endocytic recycling. J Cell Biol. 2015 Apr 13;209(1):97-110.

Brady OA, Zhou X, Hu F. Regulated intramembrane proteolysis of the frontotemporal lobar degeneration (FTLD) risk factor,TMEM106B, by Signal Peptide Peptidase-like 2a (SPPL2a). J Biol Chem. 2014 Jul 11;289(28):19670-19680.

Busch JI, Martinez-Lage M, Ashbridge E, Grossman M, Van Deerlin VM, Hu F, Lee VM, Trojanowski JQ, Chen-Plotkin AS. Expression of TMEM106B, the frontotemporal lobar degeneration-associated protein, in normal and diseased human brain. Acta Neuropathol Commun. 2013 Jul 11;1(1):36

Brady OA, Zheng, and Hu F. The Frontotemporal Lobe degeneration risk factor, TMEM106B, regulates lysosomal morphology and function. Hum Mol Genet. 2013 Feb 15;22(4):685-95.

Zheng Y, Brady OA, Meng PS, Mao Y, Hu F. C-terminus of Progranulin interacts with the beta-propeller region of Sortilin to regulate Progranulin trafficking. PLoS One 2011 Jun 15; 6(6): e21023.

Brady OA, Meng PS, Zheng Y, Mao Y, Hu F.Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1. Journal of Neurochemistry 2011 Jan; 116(2): 248-59.

Hu F, Padukkavidana T, Vætger CB, Brady OA, Zheng Y, Mackenzie IR, Feldman HH, Nykjaer A, Strittmatter SM. Sortilin-Mediated Endocytosis Determines Levels of the Frontotemporal Dementia Protein, Progranulin. Neuron 2010 Nov 18;68(4): 654-67.

Hu F and Strittmatter SM. The N-Terminal Domain of Nogo-A Inhibits Cell Adhesion and Axonal Outgrowth by an Integrin-Specific Mechanism. J Neurosci. 2008 Jan 30;28(5):1262-9.

Laurén J, Hu F, Chin J, Liao J, Airaksinen MS and Strittmatter SM. Complex ligand-receptor interactions of myelin inhibitors of axon growth with Nogo-66 receptor family members. J Biol Chem. 2007 Feb 23;282(8):5715-25.

Miao RQ, Gao Y, Harrison KD, Prendergast J, Acevedo LM, Yu J, Hu F, Strittmatter SM and Sessa WC. Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells. Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10997-1002.

Hu F, Liu B, Budel S, Chin J, Liao J, Fournier A and Strittmatter SM. Nogo-A interacts with the Nogo-66 receptor through multiple sites to create an isoform-selective subnanomolar agonist. J Neurosci. 2005 Jun 1;25(22):5298-304.

Hu F and Strittmatter SM. Regulating axon growth within the postnatal central nervous system. Semin Perinatol. 2004 Dec;28(6):371-8.

Hu F and Elledge SJ. Bub2 is a cell cycle regulated phospho-protein controlled by multiple checkpoints. Cell Cycle. 2002 Sep-Oct;1(5):351-5.

Hu F, Y. Wang, D. Liu, Y.Li, J. Qin and Elledge SJ. Regulation of Bfa1 by Cdc5 and cell cycle checkpoints. Cell 2001 Nov 30;107:655-665.