The Hu Lab
The Hu lab is interested in studying signaling pathways and mechanisms involved in neuro-degeneration.
We are interested in dissecting the disease mechanism of Frontal temporal lobe degeneration (FTLD) due to mutations in the progranulin gene. Progranulin encodes a secreted growth factor that has been implicated in wound healing and cell proliferation. But its function in the nervous system is still unclear. In FTLD patients with progranulin mutation, a DNA and RNA binding protein called TDP-43 was found to accumulate in the cytoplasm in ubiquitinated, phosphorylated and cleaved forms. We are interested in studying pathways that control progranulin trafficking and progranulin signaling. We have shown progranulin is delivered into lysosomes by sortilin. We are interested in further exploring potential functions of progranulin in lysosomes and how that’s related to neurodegeneration.
Recent studies also identified TMEM106B as a new risk factor for FTLD with progranulin mutations. Our preliminary studies have shown TMEM106B might affect lysosomal function. We are in the process of dissecting TMEM106B functions in the lysosomes and in the disease progression of FTLD with progranulin mutations.
Finally we are also investigating mechanisms involved in regulating TDP-43 aggregation and clearance using mammalian cell culture and zebrafish models.
|Postdoctoral positions are currently available. We are seeking candidates who have a strong background in biochemistry, molecular biology, cell biology, or mouse genetics with interests in neurodegeneration.
- May 2016: Our manuscript on ALS/FTLD associated protein C9orf72 is accepted for publication!
- September 2015: Our paper titled “Prosaposin facilitates sortilin independent lysosomal targeting of progranulin” is published in the Journal of Cell Biology and highlighted. Good job, Xiaolai and Lirong!
- May 2015: Welcome to DVM/Ph.D. Student, Daniel Paushter!
- September 2014: Xiaolai is awarded the Weill Institute Postdoctoral Fellowship. Congratulations!
- August 28, 2014: Peter Sullivan passed his A-exam. Congratulations!
- May 2014: Our paper on TMEM106B cleavage by SPPL2a is accepted for publication.
- Dec. 2013: Congratulations to Dr. Adam Brady for completing his PhD! Adam will take a postdoc position at NIH. Good Luck, Adam!
- April 2013: Welcome new postdoc Xiaolai Zhou, and visiting scientist Lirong Sun to the Lab!
- Dec. 2012: Fenghua is awarded research grant from MDA foundation to study TDP-43 aggregation.
- Oct. 2012: Our paper titled “The Frontotemporal Lobe degeneration risk factor, TMEM106B, regulates lysosomal morphology and function” is accepted for publication in Human Molecular Genetics.
- Sept. 2011: Fenghua is awarded AFTD 2011 Pilot Grant (http://www.theaftd.org/wp-content/uploads/2011/09/2011-Pilot-Grant-Release.pdf).
- Aug. 2011: Fenghua is granted New Investigator Award from the Alzheimer’s Association.
- June 2011: Our paper titled “C-terminus of Progranulin interacts with the beta-propeller region of Sortilin to regulate Progranulin trafficking” is published in PLoS One.
- Nov. 2010: Our paper titled “Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1” is accepted by Journal of Neurochemistry on Nov. 1st, 2010. The online version is out on Nov. 9th. Good job, Adam!
- Sept. 2010: Our joint publication with Dr. Strittmatter’s group on regulation of progranulin trafficking by sortilin is accepted by Neuron on September 7th, 2010. It will appear on the Nov. 18th issue of Neuron.
- Aug. 2010: Adam passed his A-exam on August 23rd, 2010. Congratulations, Adam!
- June 2010: Fenghua is awarded “The Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer’s Disease”.