Qun Lu, Ph.D.
Five-Year Achievement for Excellence in Research/Creative Activity Award 2009
NIH Director’s Transformative Research Award 2021
office: Brody 7N-72A
M.S., Emory University
Ph.D., Emory University
Postdoctoral Fellow, Harvard Medical School; Postdoctoral Fellow, Brigham and Women’s Hospital
The overall goal of our research is to understand how cellular functions are modulated by signaling molecules under physiological conditions and in complex human diseases. The current focus is on small G-protein signaling, with the emphasis on several classes of Ras superfamily proteins. We employ a combination of chemical biology, computer modeling, biochemistry, pharmacology, cellular imaging, and mouse genetics approaches to investigate the deregulation of Rho family small GTPases in Alzheimer’s disease and amyotrophic lateral sclerosis. We also explore regulation of Rho GTPase signaling in the anti-cancer drug induced neurodegeneration and regeneration. These investigations are leveraged upon our pioneering discovery of multifunctional pharmacological tools that modulate protein-protein interactions in the small GTPase signaling pathways in neurological disorders and cancer.
Additional information on our research scopes can be found at https://commonfund.nih.gov/TRA/recipients and from NIH press release at https://www.nih.gov/news-events/news-releases/nih-supports-106-grants-featuring-high-risk-high-reward-research.
Guiler, W., A. Koehler, C. Boykin, and Q. Lu. 2021. Pharmacological modulators of small GTPases of Rho family in neurodegenerative diseases. Front. Cell Neurosci. 15: 661612. PMID: 34054432.
Lee, S.J., M.D. Zdradzinski, P.K. Sahoo, A.N. Kar, P. Patel, R. Kawaguchi, B.J. Aguilar, K.D. Lantz, C.R. McCain, G. Coppola, Q. Lu, and J.L. Twiss. 2021. Selective axonal translation of the mRNA isoform encoding prenylated Cdc42 supports axon growth. J. Cell Sci. 134(7). PMID: 33674450.
Li, M., J. Nopparat, B.J. Aguilar, Y.H. Chen, J. Zhang, J. Du, X. Ai, Y. Luo, Y. Jiang, C. Boykin, and Q. Lu. 2020. Intratumor δ-catenin heterogeneity driven by genomic rearrangement dictates growth factor dependent prostate cancer progression. Oncogene. 39(22): 4358-4374. PMID: 32313227.
Xing, T., L.J. Benderman, S. Sabu, J. Parker, J. Yang, Q. Lu, L. Ding, and Y.H. Chen. 2020. Tight junction protein claudin-7 Is essential for intestinal epithelial stem cell self-renewal and differentiation. Cell Mol. Gastroenterol. Hepatol. 9(4):641-659. PMID: 31874254.
Zhu, Y., G.A. Howard, K. Pittman, C. Boykin, L.E. Herring, E.M. Wilkerson, K. Verbanac, and Q. Lu. 2019. Therapeutic effect of Y-27632 on tumorigenesis and cisplatin-induced peripheral sensory loss through RhoA-NF-κB. Mol. Cancer Res. 17(9): 1910-1919. PMID: 31189689.
Aguilar, B.J., Y. Zhao, H. Zhou, S. Huo, Y.H. Chen, and Q. Lu. 2019. Inhibition of Cdc42-intersectin interaction by small molecule ZCL367 impedes cancer cell cycle progression, proliferation, migration, and tumor growth. Cancer Biol. Ther. 20(6): 740-749. PMID: 30849276.
Kim, D.H., Q. Lu, and Y.H. Chen. 2019. Claudin-7 modulates cell-matrix adhesion that controls cell migration, invasion and attachment of human HCC827 lung cancer cells. Oncol. Lett. 17(3): 2890-2896. PMID: 30854065.
Do, K., B.T. Laing, T. Landry, W. Bunner, N. Mersaud, T. Matsubara, P. Li, Y. Yuan, Q. Lu, and H. Huang. 2018. The effects of exercise on hypothalamic neurodegeneration of Alzheimer’s disease mouse model. PLoS One. 13(1): e0190205. PMID: 29293568.
Kim, D.H., T. Xing , Z. Yang, R. Dudek, Q. Lu, and Y.H. Chen. 2017. Epithelial mesenchymal transition in embryonic development, tissue repair and cancer: a comprehensive overview. J. Clin. Med. 7(1). PMID: 29271928.
Aguilar B.J., Y. Zhu, and Q. Lu. 2017. Rho GTPases as therapeutic targets in alzheimers disease. Alzheimers Res. Ther. 9(1):97. PMID: 29246246.
Aguilar B.J., H. Zhou, and Q. Lu. 2017. Cdc42 signaling pathway inhibition as a therapeutic target in ras-related cancers. Curr. Med. Chem. 24 (32):3485-3507. PMID: 28571533.
Lu Q., B.J. Aguilar, M. Li, Y. Jiang, and Y.H. Chen. 2016. Genetic alterations of δ-catenin/NPRAP/Neurojungin (CTNND2): functional implications in complex human diseases. Hum. Genet. 135(10):1107-1116. PMID: 27380241.
Friesland A., Z. Weng, M. Duenas, S.M. Massa, F.M. Longo, and Q. Lu. 2014. Amelioration of cisplatin-induced experimental peripheral neuropathy by a small molecule targeting p75 NTR. Neurotoxicology. 45:81-90. PMID: 25277379.
Friesland A., Y. Zhao, Y.-H. Chen, L. Wang, H. Zhou, and Q. Lu. 2013. Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility. Proc. Natl. Acad. Sci. U S A. 110:1261-1266.
Zhang G., L. Ding, R. Renegar, X. Wang, Q. Lu, S. Huo, and H.-Y. Chen. 2011. Hydroxycamptothecin-loaded Fe3O4 nanoparticles induce human lung cancer cell apoptosis through caspase-8 pathway activation and disrupt tight junctions. Cancer Sci. 102:1216-1222.
Lu Z., L. Ding, H. Hong, J. Hoggard, Q. Lu, and Y.-H. Chen. 2011. Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathway. Exp. Cell Res. 317:1935-1946.
Boykin C., G. Zhang, Y.-H. Chen, R.W. Zhang, X.E. Fan, W.M. Yang, and Q. Lu. 2011. Cucurbitacin IIa: a novel class of anti-cancer drug inducing non-reversible actin aggregation and inhibiting surviving independent of JAK2/STAT3 phosphorylation. Br. J. Cancer 104:781-789.
Lu J., J. Zhang, K. Kim, T. Case, R. Matusik, M. Caudy, M. Wolfe, Y.-H. Chen, J. Nopparat, and Q. Lu. 2010. Human homolog of Drosophila Hairy and enhancer of split 1, Hes1, negatively regulates delta-catenin (CTNND2) expression in cooperation with E2F1 in prostate cancer. Molec. Cancer 9:304.
James S.E., M. Dunham, M. Carrion-Jones, A. Murashov A, and Q. Lu. 2010. Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin. Neurotoxicology 31: 188-194.
Lu Q. 2010. δ-Catenin dysregulation in cancer: interactions with E-cadherin and beyond. J. Pathol. 222:119-123.
Bareiss S.K., K. Kim, and Q. Lu. 2010. δ-Catenin/NPRAP: a new member of the glycogen synthase kinase-3β signaling complex that promotes β-catenin turnover in neurons. J. Neurosci. Res. 88:2350-2363.
Zhang J., Y.-H. Chen, and Q. Lu. 2010. Pro-oncogenic and anti-oncogenic pathways: opportunities and challenges of cancer therapy. Future Oncol. 6: 587-603.
Lu Q., C. Boykin, D. Kai, M.P. Frosch, S. Jones, M. Wolfe, and G.W. Lanford.2010. Alzheimer disease-linked presenilin mutation (PS1M146L) induces filamin expression and γ-secretase independent redistribution. J. Alzheimer Dis. 22: 235-245.
Yang I., O. Chang, Q. Lu, and K. Kim. 2010. δ-Catenin affects the localization and stability of p120-catenin by competitively interacting with E-cadherin. Mol. Cells 29: 1-10.
Dunham M.W., S.E. James, T.E. Lever, Q. Lu, and M.J. Carrion-Jones. 2009. Methodology to obtain a sensory component of the sciatic nerve in mice. Am. J. Phys. Med. Rehab. 88:542-546.
Oh M., H. Kim, I. Yang, S. Bareiss, H. Ki, Q. Lu, J. No, I. Kwon, and K. Kim. 2009. GSK-3 phosphorylates δ-catenin and negatively regulates its stability via ubiquitination/proteosome-mediated proteolysis. J. Biol. Chem. 284: 28579-28589.
Wang T., Y.-H. Chen, H. Hong, S. Bareiss, B. Jeansonne, and Q. Lu. 2009. Increased nucleotide polymorphic changes in the 5′-untranslated region of δ-catenin (CTNND2) gene in prostate cancer. Oncogene 28: 555-564.
Zeng Y., A. Abdallah, J.P. Lu, T. Wang, Y.-H. Chen, D.M. Terrian, K. Kim, and Q. Lu. 2009. δ-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles. Molec. Cancer. 8:19.
Baulac S., H. Lu, J. Strahle, T. Yang, M.S. Goldberg, J. Shen, M.G. Schlossmacher, C.A. Lemere, Q. Lu, and W. Xia. 2009. Increased DJ-1 expression under oxidative stress and in Alzheimer’s disease brains. Molec. Neurodegen. 4:12.
Lu Q., J. Zhang, R. Allison, H. Gay, W.X. Yang, N. Bhowmick, G. Frelix, S. Shappell, and Y.-H. Chen. 2009. Identification of extracellular δ-catenin accumulation for prostate cancer detection. The Prostate 69:411-418.
Lu Q., F.M. Longo, H.C. Zhou, S.M. Massa, and Y.-H. Chen. 2009. Signaling through Rho GTPase pathway as viable drug target. Curr. Med. Chem. 16:1355-1365.
Yang T., J. Knowles, Q. Lu, J. Rajadas, G. Fuller, Q. Wang, K. Andreasson, L. Moore, T. Chang, S.M. Massa, and F.M. Longo. 2008. Small molecule, non-peptide p75NTR ligands inhibit Aβ-induced neurodegeneration. PLoS ONE 3: e3604.
James S.E., H. Burden, R. Burgess, Y. Xie, T. Yang, S.M. Massa, F.M. Longo, and Q. Lu. 2008. Anti-cancer drug induced neurotoxicity and identification of Rho pathway signaling modulators as potential neuroprotectants. Neurotoxicology 29:605-612.
Kim H., M. Oh, Q. Lu, and K. Kim. 2008. E-Cadherin negatively modulates δ-catenin-induced morphological changes and RhoA activity reduction by competing with p190RhoGEF for δ-catenin. Biochem. Biophys. Res. Commun. 377:636-641.
Kim H., J.R. Han, J. Park, M. Oh, S.E. James, S. Chang, Q. Lu, K.Y. Lee, H. Ki, W.J. Song, and K. Kim. 2008. Delta-catenin-induced dendritic morphogenesis: an essential role of p190RhoGEF interaction through Akt1-mediated phosphorylation. J. Biol. Chem. 283:977-987.
Kim J., S.K. Bareiss, K.K. Kim, R. Tatum, J. Han, Y.H. Jin, H. Kim, Q. Lu*, and K. Kim. 2006. Presenilin-1 inhibits δ-catenin-induced cellular branching and promotes δ-catenin processing and its turnover. 2006. Biochem. Biophys. Res. Commun. 351:903-908. (*co-correspondence).
Lu Q., L.J. Dobbs, W.G. Christopher, G.W. Lanford, M.P. Revelo, S. Shappell, and Y.-H. Chen. 2005. Increased expression of δ-catenin/neural plakophilin-related armadillo protein (NPRAP) is associated with the downregulation and redistribution of E-cadherin and p120ctn in human prostate cancer. Hum. Pathol. 36: 1037-1048.
Jones S.B., H.Y. Lu, and Q. Lu. 2004. Abl tyrosine kinase promotes dendrogenesis by inducing actin cytoskeletal rearrangements in cooperation with Rho family small GTPases in hippocampal neurons. J. Neurosci. 24:8510-8521.
Jones S.B., A. Sirota, Y.-H. Chen, K. Kim, G.W. Lanford, M. Moribito, and Q. Lu. 2002. Glutamate-induced &delta-catenin redistribution and dissociation from postsynaptic receptor complexes. Neuroscience 115: p1009-1021.
Kim K., A. Sirota A, Y.-H. Chen, S.B. Jones, R. Dudek, G.W. Lanford, C. Thakore, and Q. Lu. 2002. Dendrite-like process formation and cytoskeletal remodeling regulated by δ-catenin expression. 2002. Exp. Cell Res. 275: 171-184.
Lu Q., N. Mukhopadhyay, J. Griffin, M. Paredes, M. Medina, and K.S. Kosik. 2002. Brain armadillo protein δ-catenin interacts with Abl tyrosine kinase and modulates cellular morphogenesis in response to growth factors. J. Neurosci. Res. 67: 618-624.
Flaherty D., Q. Lu, J. Soria, and J.G. Wood. 1999. Regulation of tau phosphorylation in microtubule fractions by apolipoprotein E. J. Neurosci. Res. 56: 271-274.
Lu Q., M. Paredes, M. Medina, J.H. Zhou, R. Cavallo, M. Peifer, L. Orecchio, and K.S. Kosik. 1999. δ-catenin, an adhesive junction associated protein which promotes cell scattering. J. Cell Biol. 144: 1-14.
Ferreira A., Q. Lu, L. Orecchio, and K.S. Kosik. 1997. Selective phosphorylation of adult tau isoforms in mature hippocampal neurons exposed to fibrillar Aβ. Molec. Cell Neurosci. 9: 220-234.
Lu Q. and J.G. Wood. 1993. Functional studies of Alzheimer’s disease tau protein. J. Neurosci. 13: 508-515.
Lu Q., J.P. Soria, and J.G. Wood. 1993. p44mpk MAP kinase induces Alzheimer type alterations in tau function and in primary hippocampal neurons. J. Neurosci. Res. 35: 439-444.
“Homeostatic Reset as a New Therapeutic Paradigm for Slow Progression Diseases” (NIH R01 GM146257); Qun Lu, Principal Investigator; National Institute of General Medicine Sciences and NIH Office of Director; 09/15/2021-08/31/2026.
Staff and Students
|Shayan Nik Akhtar||Graduate Studentemail@example.com
|Dr. Fereshteh Azimian||Postdoctoral Scholarfirstname.lastname@example.org|
|Christi Boykin||Research Technicianemail@example.com|
|Katy L. Davis||Graduate Studentfirstname.lastname@example.org|
|Addison Koehler||Undergraduate Studentemail@example.com|
|Dr. Satya Malasala||Postdoctoral Scholarfirstname.lastname@example.org|
|Timothy Penwell||Graduate Studentemail@example.com|
Former Students and Post-Doctoral Fellows
|Sonja Bareiss, P.T., Ph.D.||Associate Professor||Department of Physical Therapy, Ballarmine University, Louisville, KY|
|Amy Friesland Potter, Ph.D.||Lecturer||Department of Biological Sciences, North Carolina State University, Raleigh, NC|
|Sarah James, Ph.D., M.D.||Radiation Oncologist||Mayo Clinic Department of Radiation Oncology, Albert J. and Judith A. Dunlap Cancer Center, Eau Claire, WI|
|Shiloh Jones, Ph.D.||Associate Professor||Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC|
|Kwonseop Kim, Ph.D.||Professor||College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea|
|Jian Ping Lu, Ph.D.||Professor||College of Life Sciences, Zhejiang University, Hangzhou, China|
|Tao Wang, Ph.D., M.D.||Professor||Department of General Surgery, Nanjing Medial University, Nanjing, China|
|Zhiying (Jean) Weng, Ph.D, M.D.||Associate Professor||School of Pharmacy, Kunming Medical University, Kunming City, China|
|Yi (Neo) Zhu, Ph.D.||Postdoctoral Research Fellow||Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA|
|Byron Aguilar, Ph.D.||Scientist||Boston University School of Medicine and Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA|