Wenhui Hu
Wenhui Hu, MD, MS, PhD
Associate Professor of Neuroscience

Temple University
USA

Education

2001-2002 Postdoc Neurosurgery/Neuroimmunology (John R. Bethea) Miami Project to Cure Paralysis, University of Miami, Miami, FL
1999-2000 Associate Postdoc Molecular Biology/ Immunology (Hongbing Shu) National Jewish Medical and Research Center, University of Colorado, Denver, CO
1996 Ph.D. Molecular Neurobiology (Minfeng Jen) Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
1988 M.S. Traumatic Surgery (Yingbing Liu) Third Military Medical University, Chongqing, China
1979 M.D. Medicine North Sichuan Medical College, Sichuan, China

 

Biography

His postdoctoral training identifieda novel function of the apoptosis-inducing proteins FADD, Casper and Caspase-8 to activate NFB signaling. Then he discovered several novel proteins (NIBP, TNAP, etc.) that modulate NFkB signaling and one new mitochondrial protein NIMP that may regulate neural regeneration. At his early stage of faculty, Dr. Hudemonstrated that RGS4 is a novel NFB target gene that is also modulated by MAPKs and PI3K/GSK3β pathways. He identified a new function of NFkB signaling to initiate early differentiation of neural stem cells. His current research focuses the novel role and mechanism of NIBP/TRAPPC9 in neurogenesis and neuronal polarization. He has very active and productive collaboration with national and international scientists. His collaboration with Dr. Marenda at Drexel University identified a novel function of TCF4 to restrict neurite branching of postmitotic neurons. In the past 2-3 years, his collaboration with Dr. Kamel Khalili at Temple University demonstrated that Cas9/gRNA-mediated genome editing can effectively and specifically eradicate latently-infected HIV proviruses. This finding induced a huge global media responseand was ranked top 100 discovery in 2014 by “Discover” magazine. This year, Dr. Hu also reported for the first time that the dCas9-SAM technology can induce specific and robust suicide death of HIV latent cells. Dr. Hu currently is Associate Professor of Neuroscience and Neurovirology at Temple University Lewis Katz School of Medicine.He teaches Molecular and Cellular Neuroscience, and Translational Science of Nervous System Disease. His research is currently funded by three active NIH-R01 grants, focusing on neurodevelopmental disorders, gastrointestinal neuromuscular regulation and HIV/AIDS cure.  Dr. Hu has published more than 70 papers and holds 4 patents. Specific area of his expertise includes molecular cloning, RNA interference, Cas9-mediated genome editing, virus-mediated gene therapy, brain and enteric neural stem cell culture, conditional knockout or knockin mouse models, neural behavior test, cell-based functional assays, confocal imaging, and HIV eradication/reactivation.

Research Interest

  • Gene transcription and mRNA stability (NIBP, TCF4 and RGS4)
  • Signal transduction (NFB, trans-Golgi networkand G protein signaling)
  • Neural Plasticity
  • Neuro immunity
  • Embryonic and adult neurogenesis
  • Neuronal polarization
  • Spinal cord injury and neuroregeneration
  • Mental retardation
  • Autism
  • Schizophrenia
  • Pitt-Hopkins syndrome
  • Neurodegenerative diseases
  • HIV latent reservoir and Neuro AIDS

Professional Activities:

2013 Associate Professor Department of Neuroscience Temple University, Philadelphia, PA
2008-2013 Assistant Professor Department of Neuroscience Temple University, Philadelphia, PA
2007 Visiting Associate and Full Professor West China Hospital Sichuan University, Chengdu, China
2004-2008 Assistant Professor Department of Physiology Virginia Commonwealth University, Richmond, VA
2002-2004 Senior Scientist Miami Project to Cure Paralysis University of Miami, Miami, FL
1996-1999 Associate Professor Research Institute of Surgery and Daping Hospital The Third Military Medical University, Chongqing, China
1988-1993 Research Associate Research Institute of Surgery and Daping Hospital The Third Military Medical University, Chongqing, China
1982-1985 Medical Residency Internal Medicine, 520 Hospital National Committee for Science and Technology, Sichuan, China

 

Publications

  1. D’Rozario M, Zhang T, Waddell EA, Zhang YG, Sahin C, Sharoni M, Hu T, Naya M, Kutty K, Lieb F, Hu WH*, and Marenda DR. Type I bHLH proteins Daughterless and TCF4 restrict neurite branching and synapse formation by repressing Neurexin in postmitotic neurons. Cell Reports, 2016, in print.
  2. Feng D, Shen D, Liu F, Ohtake Y, Zhou A, Wang H, Zhang Y, Kearns A, Peng X, Zhu F, Hayat U, Li M, He Y, Xu M, Zhao C, Cheng M, Zhang L, Wang H, Yang X, Ju C, Bryda EC, Gordon J, Khalili K, Hu WH, Li S, Qin X and Gao B. Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration. J Clinical Investigation 2016, in print.
  3. Yin CR, Zhang T, Li F, Yang F, Putatunda R, Young WB, Khalili K, Hu WH*, and Zhang YG. Functional screening of guide RNAs targeting the regulatory and structural HIV-1 viral genome for a cure of AIDS. AIDS, 2016, in print
  4. Kaminski R, Chen Y, Fischer T, Tedaldi E, Napoli A, Zhang Y, Karn J, Hu WH*, Khalili K. Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing. Scientific Reports, 2016 Mar 4;6:22555.
  5. Zhang YG, Li F, Wang H, Yin CY, Huang J, Mahavadi S, Murthy KS, Hu WH*. Immune/Inflammatory Response and Hypocontractility of Rabbit Colonic Smooth Muscle After TNBS-Induced Colitis. Dig Dis Sci. 2016 Feb 15. [Epub ahead of print]
  6. Zhang YG, Yin CR, Zhang T, Li F, Yang WS, Kaminski R, Fagan P, Putatunda R, Young WB, Khalili K, and Hu WH*. CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoir. Scientific Reports, 2015 Nov 5; 5:16277.
  7. Zhu Y, Lin Y, Liu A, Shui M, Li R, Liu X, Hu WH, Wang Y. Structure-guided creation of AcAP5-derived and platelet targeted factor Xa inhibitors. Biochem Pharmacol. 2015 Jun 15;95(4):253-62. doi: 10.1016/j.bcp.2015.04.004. Epub 2015 Apr 15.
  8. McCaffrey J, Sibert J, Zhang B, Zhang Y, Hu WH, Riethman H, Xiao M. CRISPR-CAS9 D10A nickase target-specific fluorescent labeling of double strand DNA for whole genome mapping and structural variation analysis. Nucleic Acids Res. 2015 Oct 19. pii: gkv878. [Epub ahead of print]
  9. White MK, Hu WH, Khalili K. The CRISPR/Cas9 genome editing methodology as a weapon against human viruses. Discov Med. 2015 Apr;19(105):255-62.
  10. Wollebo HS, Bellizzi A, Kaminski R, Hu WH, White MK, Khalili K. CRISPR/Cas9 System as an Agent for Eliminating Polyomavirus JC Infection. PLoS One. 2015 Sep 11;10(9):e0136046. doi: 10.1371/journal.pone.0136046. eCollection 2015.
  11. Khalili K, Gordon J, Kaminski R, Cosentino L, Hu WH*. Genome editing strategies: potential tools for eradicating HIV-1/AIDS. J Neurovirol. 2015 Feb 26. [Epub ahead of print]
  12. Zhang YG, Liu S, Wang H, Yang WS, Li F, Yang F, Yu DH, Ramsey FV, Tuszyski GP, Hu WH*. Elevated NIBP/TRAPPC9 mediates tumorigenesis of cancer cells through NFκB signaling. OncoTarget 2015, 2015 Jan 31. [Epub ahead of print] PMID: 25704885
  13. Hu WH*, Kaminski R, Yang F, Zhang YG, Cosentino L, Li F, Luo B,  Alvarez-Carbonell D, Garcia Y, Karn J, Mo XM, and Khalili K. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. PNAS 2014; 111(31):11461-6. Huge global media response with the Altmetric score 325.80: http://www.altmetric.com/details.php?domain=www.pnas.org&citation_id=2526844. Ranked 2014 discovery at #86 among 100 top stories by “Discover” magazine. http://news.temple.edu/news/2015-01-08/temple-aids-discovery-among-top-100-science-stories-2014
  14. Rajagopal S, Nalli AD, Kumar DP, Bhattacharya S, Hu WH, Mahavadi S, Grider JR, Murthy KS. Cytokine-Induced S-Nitrosylation of Soluble Guanylyl Cyclase and Expression of Phosphodiesterase 1A Contribute to Dysfunction of Longitudinal Smooth Muscle Relaxation. J Pharmacol Exp Ther. 2014 Sep 9. pii: jpet.114.218156
  15. Zhang YG, Bitner D, Pontes A, Li F, Liu S, Wang H, Yang F, Adhikari S, Gordon J, Srinivasan S, Hu WH*. Expression and function of NIK- and IKK2-binding protein (NIBP) in mouse enteric nervous system. Neurogastroenterology Motility 2014; 26(1):77-97.
  16. Mahavadi S, Nalli AD, Kumar DP, Hu WH, Kuemmerle JF, Grider JR, Murthy KS. Cytokine-induced iNOS and ERK1/2 inhibit AC5/6 activity and stimulate PDE4D5 activity in intestinal longitudinal smooth muscle. Am J Physiol Cell Physiol. 2014 Jun 18. pii: ajpcell.00123.2014
  17. Zhu Y, Bu Q, Liu X, Hu WH, Wang Y. Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats. PLoS One. 2014 Mar 26;9(3):e93334.
  18. Zhang, Y. and Hu WH*. Mouse Enteric Neuronal Cell Culture. Neuronal Cell Culture. S. Amini and M. K. White (Ed), ISBN: 978-1-62703-639-9, Humana Press, 2013. DOI: 10.1007/978-1-62703-640-5_6. Method in Molecular Biology 2013; 1078: 55-63
  19. Hu WH and Luo JJ. Research Advances in Pick’s Disease: A New Biomarker Candidate.  J Neurol Neurophysiol 2013; 4:1. http://dx.doi.org/10.4172/2155-9562.1000e112 (Editorial)
  20. Pontes A, Zhang Y and Hu WH*. Novel functions of GABA signaling in adult neurogenesis. Front Biol 2013; DOI 10.1007/s11515-013-1270-2 (Review)
  21. Zhang Y and Hu WH*. NFκB signaling directs neuronal fate decision. In: Wislet-Gendebien S (ed): Trends in Cell Signaling Pathways in Neuronal Fate Decision. InTech 2012, ISBN 980-953-307-601-5
  22. Zhang Y and Hu WH*. NFB signaling regulates embryonic and adult neurogenesis. Front Biol 2012; DOI 10.1007/s11515-012-1233-z
  23. Zhang Y, Liu J, Yao S, Li F, Xin L, Lai M, Bracchi-Ricard V, Xu H, Yen W, Meng W, Liu S, Yang L, Karmally S, Zhu H, Gordon J, Khalili K, Srinivasan S, Bethea JR, Mo X, Hu WH*. Nuclear factor kappa B signaling initiates early differentiation of neural stem cells. Stem Cells 2012;30:510-524. (IF:7.871)(cited by 1)
  24. Zhang Y, Li F, Liu S, Wang H, Mahavadi S, Murthy KS, Khalili K, Hu WH*. MEKK1-MKK4-JNK-AP1 Pathway Negatively Regulates Rgs4 Expression in Colonic Smooth Muscle Cells. PLoS One 2012;7:e35646. (IF:4.411)
  25. Sun D, Gugliotta M, Rolfe A, Reid W, McQuiston AR, Hu WH, Young H. Sustained survival and maturation of adult neural stem/progenitor cells after transplantation into the injured brain. J Neurotrauma 2011;28:961-972. (IF:3.426)
  26. Li F, Murthy KS, Khalili K, Hu WH*. Cloning and characterization of rabbit Rgs4 promoter in gut smooth muscle. Gene 2010;451:45-53. (IF:2.266) (cited by 3)
  27. Li F, Hu DY, Liu S, Mahavadi S, Yen W, Murthy KS, Khalili K, Hu WH*. RNA-binding protein HuR regulates RGS4 mRNA stability in rabbit colonic smooth muscle cells. Am J Physiol Cell Physiol 2010;299:C1418-1429. (IF:3.817) (cited by 3)
  28. Kuang X, Hu WH, Yan M, Wong PK. Phenylbutyric acid suppresses protein accumulation-mediated ER stress in retrovirus-infected astrocytes and delays onset of paralysis in infected mice. Neurochem Int 2010;57:738-748. (IF:3.601) (cited by 2)
  29. Hu WH*, Li F, Mahavadi S, Murthy KS. Upregulation of RGS4 expression by IL-1beta in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3beta pathway. Am J Physiol Cell Physiol 2009;296:C1310-1320. (IF:3.817) (cited by 11)
  30. Hu WH*, Li F, Mahavadi S, Murthy KS. Interleukin-1beta up-regulates RGS4 through the canonical IKK2/IkappaBalpha/NF-kappaB pathway in rabbit colonic smooth muscle. Biochem J 2008;412:35-43. (IF:5.016) (cited by 15)
  31. Bracchi-Ricard V, Brambilla R, Levenson J, Hu WH, Bramwell A, Sweatt JD, Green EJ, Bethea JR. Astroglial nuclear factor-kappaB regulates learning and memory and synaptic plasticity in female mice. J Neurochem 2008;104:611-623. (IF:4.337) (cited by 19)
  32. Zhou H, Jarujaron S, Gurley EC, Chen L, Ding H, Studer E, Pandak WM, Jr., Hu WH, Zou T, Wang JY, Hylemon PB. HIV protease inhibitors increase TNF-alpha and IL-6 expression in macrophages: involvement of the RNA-binding protein HuR. Atherosclerosis 2007;195:e134-143. (IF:4.086) (cited by 21)
  33. Song Y, Wilkins P, Hu WH, Murthy KS, Chen J, Lee Z, Oyesanya R, Wu J, Barbour SE, Fang X. Inhibition of calcium-independent phospholipase A2 suppresses proliferation and tumorigenicity of ovarian carcinoma cells. Biochem J 2007;406:427-436. (IF:5.016) (cited by 33)
  34. Hu WH*, Mahavadi S, Li F, Murthy KS. Upregulation of RGS4 and downregulation of CPI-17 mediate inhibition of colonic muscle contraction by interleukin-1beta. Am J Physiol Cell Physiol 2007;293:C1991-2000. (IF:3.817) (cited by 13)
  35. Yan D, Li F, Hall ML, Sage C, Hu WH, Giallourakis C, Upadhyay G, Ouyang XM, Du LL, Bethea JR, Chen ZY, Yajnik V, Liu XZ. An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C). J Mol Biol 2006;357:755-764. (IF:4.008) (cited by 16)
  36. Huang J, Mahavadi S, Sriwai W, Hu WH, Murthy KS. Gi-coupled receptors mediate phosphorylation of CPI-17 and MLC20 via preferential activation of the PI3K/ILK pathway. Biochem J 2006;396:193-200. (IF:5.016) (cited by 46)
  37. Hu WH, Mahavadi S, Huang J, Li F, Murthy KS. Characterization of S1P1 and S1P2 receptor function in smooth muscle by receptor silencing and receptor protection. Am J Physiol Gastrointest Liver Physiol 2006;291:G605-610. (IF:3.522) (cited by 21)
  38. Hu WH, Huang J, Mahavadi S, Li F, Murthy KS. Lentiviral siRNA silencing of sphingosine-1-phosphate receptors S1P1 and S1P2 in smooth muscle. Biochem Biophys Res Commun 2006;343:1038-1044. (IF:2.595) (cited by 17)
  39. Hu WH*, Pendergast JS, Mo XM, Brambilla R, Bracchi-Ricard V, Li F, Walters WM, Blits B, He L, Schaal SM, Bethea JR. NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation. J Biol Chem 2005;280:29233-29241. (IF:5.328) (cited by 39)
  40. Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ, Bethea JR. Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 2005;202:145-156. (IF:14.776) (cited by 126)
  41. Hu WH*, Mo XM, Walters WM, Brambilla R, Bethea JR. TNAP, a novel repressor of NF-kappaB-inducing kinase, suppresses NF-kappaB activation. J Biol Chem 2004;279:35975-35983. (IF:5.328) (cited by 29)
  42. Hu WH*, Walters WM, Xia XM, Karmally SA, Bethea JR. Neuronal glutamate transporter EAAT4 is expressed in astrocytes. Glia 2003;44:13-25. (IF:5.186) (cited by 34)
  43. Hu WH*, Hausmann ON, Yan MS, Walters WM, Wong PK, Bethea JR. Identification and characterization of a novel Nogo-interacting mitochondrial protein (NIMP). J Neurochem 2002;81:36-45. (IF:4.337) (cited by 35)
  44. Hausmann ON, Hu WH, Keren-Raifman T, Witherow DS, Wang Q, Levay K, Frydel B, Z Slepak V, R Bethea JR. Spinal cord injury induces expression of RGS7 in microglia/macrophages in rats. Eur J Neurosci 2002; 15(4):602-612. (IF:3.658) (cited by 11)
  45. Qiang WA, Sun L, Hu WH, Zuo P, Ren MF and Liu JS. Effects of high dose of dynorphin on NMDA receptor and NOS activities in spinal cord of rats. Acta Academiae Medicinae Sinicae 2000; 22(2):134-138.
  46. Hu WH, Liu N, Li F, Qiang WA, LiaoWH and Ren MF.  Effects of kappa-opioid receptor on dynorphin-induced spinal cord injury. Chin J Traumatol 2000; 16(5): 286-288. 
  47. Hu WH, Qiang WA, Li F, Liu N, Wang GQ, Wang HY, Wan XS, Liao WH, Liu JS, Jen MF. Constitutive and inducible nitric oxide synthases after dynorphin-induced spinal cord injury. J Chem Neuroanat 2000;17:183-197. IF:2.121) (cited by 17)
  48. Hu WH, Johnson H, Shu HB. Activation of NF-kappaB by FADD, Casper, and caspase-8. J Biol Chem 2000;275:10838-10844. (IF:5.328) (cited by 231)
  49. Zeng C, Zhu Z, Hu WH, Liu G, Zhu S, Zhou Y, Shi W. Value of sublingual isosorbide dinitrate before isoproterenol tilt test for diagnosis of neurally mediated syncope. Am J Cardiol 1999;83:1059-1063. (IF:3.681) (cited by 26)
  50. Shu HB, Hu WH, Johnson H. TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. J Leukoc Biol 1999;65:680-683. (IF:4.626) (cited by 336)
  51. Hu WH*, Li F, Qiang WA, Liu N, Wang GQ, Xiao J, Liu JS, Liao WH, Jen MF. Dual role for nitric oxide in dynorphin spinal neurotoxicity. J Neurotrauma 1999;16:85-98. (IF:3.426) (cited by 24)
  52. Hu WH, Johnson H, Shu HB. Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-kappaB and JNK activation and apoptosis through distinct pathways. J Biol Chem 1999;274:30603-30610. (IF:5.328) (cited by 211)
  53. Hu WH*, Yang HF, Li F, Qiang WA, Sun XJ, Liu N, Wan XST, Liu JS and Ren MF. Increases of inducible nitric oxide synthase activity and mRNA expression in rat spinal cord after dynorphin neurotoxicity. Chin J Pathophysiol 1999; 15(3):217-221.
  54. Li F, Hu WH, Liu N, Qiang WA, Sun XJ,  Wan XST, Liu JS and Jen MF. Role of neuronal nitric oxide synthase in dynorphin spinal neurotoxicity and analgesia in rats. Nat. Med. J. Chin 1999; 79(3):217-220
  55. Hu WH, Zhang CH, Yang HF, Zheng YF, Liu N, Sun XJ and Jen MF. Dualistic effect of dynorphin on high potassium-induced increase of intracellular free calcium concentration in cultured rat spinal neurons. Chin J Pharmacol Toxicol 1998; 12(1):32-35
  56. Hu WH, Zhang CH, Yang HF, Zheng YF, Liu N, Sun XJ, Jen J, Jen MF. Mechanism of the dynorphin-induced dualistic effect on free intracellular Ca2+ concentration in cultured rat spinal neurons. Eur J Pharmacol 1998;342:325-332. (IF:2.737) (cited by 17)
  57. Hu WH, Liu N, Sun XJ, Jen J, Yang HF and Jen MF. L-NAME aggravates dynorphin-induced spinal cord injury in rats. Chin J Neurosci 1997; 4(3):115-119
  58. Li FC, Zuo PP, Hu WH, Liu N, Jen MF. Glutamate involvement in rats with spinal cord injury induced by dynorphin A(1-17). Chin J. Rehabil. Theory and Practice 1997; 3:6-9.
  59. Hu WH. [Effects of dynorphin A1-17 on the activities, immunoreactivities and mRNA expression of cNOS and iNOS in rat spinal cord and their mechanisms]. Sheng Li Ke Xue Jin Zhan 1997;28:45-48.
  60. Hu WH, Lee FC, Wan XS, Chen YT, Jen MF. Dynorphin neurotoxicity induced nitric oxide synthase expression in ventral horn cells of rat spinal cord. Neurosci Lett 1996;203:13-16. (IF:2.055) (cited by 18)
  61. Hu WH, Sun XJ, Wan XST, Liu JS and Jen MF. Intrathecal administration of NOS inhibitor L-NAME produced algesia, analgesia and paralysis in rat. Chin Pharmacol Bull 1996; 12(4):309-313
  62. Li F, Hu WH, Liao WH and Jen MF. Nitric oxide mediates NMDA neurotoxicity in rat primary spinal culture. Chin J Neurosci 1995; P245
  63. Hu WH, Yang HW, Wang YJ and Liao WH. Segmental distribution of electrocytes and water in spinal cord after ischemia-reperfusion injury in conscious rabbits. Acta Academiae Medicinae Militaris Tertiae  1995; 17(4):315-317
  64. Li FC, Sun XJ, Hu WH and Jen MF. Intrathecal coadministration of kappa opioid receptor agonists and NMDA receptor antagonist induced synergetic analgesia in rat. Acta Pharmaceutia Sinica 1994; 29(12):881-886
  65. Hu WH, Yang HW and Liao WH. The effects of neurotransmitter and non-neurotransmitter amino acids in secondary injury after spinal cord ischemia in awake rabbits. Acta Academiae Medicinae Militaris Tertiae  1994; 16(3):170-4
  66. Hu WH, Yang HW, Wang YJ and Liao WH. The effect of ion changes and edema formation during secondary injury following spinal cord ischemia in awaken rabbit. Chin J Pathophysiol 1994;10(6):659
  67. Hu WH, Yang HW, Lu XB and Liao WH.  Neurobehavioral outcome of spinal cord delayed postischemic injury in awaken rabbits. Chin J Pathophysiol 1993; 9(4):483
  68. Yang HW, Hu WH, Ding ZM and Liu YB. Changes of spinal cord blood flow after ventral spinal cord injury in rats. Chinese J Neurosurg 1991; 7(2):87
  69. Hu WH, Liu YB, Yang CQ, et al. Measurement of blood flows to gray and white matter of segmental spinal cord with radioactive biomicrosphere technique.  Chin J Neurosurg 1990