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Education

M.S., 1992, Emory University
Ph.D., 1993, Emory University
Postdoc., 1997, Harvard Medical School and Brigham and Women’s Hospital

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Honors and Awards

The Outstanding Faculty, 2022; NIH Director’s Transformative Research Award, 2021; The Albert Nelson Marquis Lifetime Achievement Award, 2018; The Inventor Recognition, East Carolina University, 2018; Inductee of National Academy of Inventors, 2012; UNC Tomorrow Technology Initiative Implementation Task Force, 2010; Inaugural Inventor Award, East Carolina University, 2009; Five-Year Achievement in Excellence in Research/Creative Award, East Carolina University, 2009; Inaugural William E. Laupus Library Faculty Author Recognition Award, 2005; Helms Award for Outstanding Research, Sigma X Scientific Society, 2005; Finalist for Clifford Barger Excellence in Mentoring Award, Harvard Medical School, 1998; Sigma Xi Award for Outstanding Graduate Research, Sigma X Scientific Society, 1992.

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Research

The overall goal of our research at the Center for Neurotherapeutics is to understand how cellular functions are modulated by signaling molecules under physiological conditions and in complex neurological diseases. With the better understanding of underlying molecular mechanisms of disease progression, we develop and investigate next generation neurotherapeutics. The current focus is on small G-protein signaling, with the emphasis on several classes of Ras superfamily proteins. We employ a combination of modern technologies in chemical biology, computer modeling, biochemistry, pharmacology, cellular imaging, and mouse genetics to investigate the deregulation of small GTPases of Rho, Rab, and Arf subfamilies in Alzheimer’s disease and related dementias (ADRD) as well as amyotrophic lateral sclerosis (ALS). These investigations are built on the following areas of researches:
(I). Small GTPase expression and functions are dysregulated in a spatial and temporal manner in diseased brain. This is established by a series of studies employing confocal and super-resolution fluorescence imaging, computational analysis with AI/ML toolboxes, and transcriptomic and barcoding technologies. 
(II). The spatial and temporal dysregulation supports novel concept of homeostatic modulation as a therapeutic paradigm. Our translational research, leveraged by the pioneering discovery of multifunctional small molecule homeostatic modulators (HMs) of small GTPases, applies CADD (Schrödinger software), biochemical (Biacore 1S+ SPR and activity-based ELISA) and pre-clinical (Cell-based assay and mouse genetics) validation to target ADRD and ALS. 
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.

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Selected Publications (Since 2010)

Linseman DA, Lu Q. Editorial: Rho family GTPases and their effectors in neuronal survival and neurodegeneration. Front Cell Neurosci. 2023;17:1161072. https://doi.org/10.3389/fncel.2023.1161072.

Nik Akhtar S, Lu Q. RhoA-LIMK Signaling Axis Reveals Rostral-Caudal Plane and Spatial Dysregulation in the Brain of Alzheimer's Disease Mouse Models. J Alzheimers Dis. 2023;95(4):1643.

Nik Akhtar S, Bunner WP, Brennan E, Lu Q, Szatmari EM. Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders. Frontiers in Cellular Neuroscience. 2023;17. https://doi.org/10.3389/fncel.2023.1084769.

Lu Q, Chen YH. TRPV4: En RhoA To a Cure? Bioessays. 2022;44(6):e2200071. http://doi.org/10.1002/bies.202200071.

Naser AN, Guiler W, Lu Q, Chen YH. Nanoarchitecture and molecular interactions of epithelial cell junction proteins revealed by super-resolution microscopy. Ann N Y Acad Sci. 2022;1516(1):175. https://doi.org/10.1111/nyas.14855.

Guiler W, Koehler A, Boykin C, Lu Q. Pharmacological Modulators of Small GTPases of Rho Family in Neurodegenerative Diseases. Front Cell Neurosci. 2021;15:661612. https://doi.org/10.3389/fncel.2021.661612.

Bareiss SK, Johnston T, Lu Q, Tran TD. The effect of exercise on early sensorimotor performance alterations in the 3xTg-AD model of Alzheimer's disease. Neurosci Res. 2022;178:60.

Lee SJ, Zdradzinski MD, Sahoo PK, Kar AN, Patel P, Kawaguchi R, et al. Selective axonal translation of the mRNA isoform encoding prenylated Cdc42 supports axon growth. J Cell Sci. 2021;134(7). https://doi.org/10.1242/jcs.251967.

Li M, Nopparat J, Aguilar BJ, Chen YH, Zhang J, Du J, et al. Intratumor δ-catenin heterogeneity driven by genomic rearrangement dictates growth factor dependent prostate cancer progression. Oncogene. 2020;39(22):4358.

Zhu Y, Howard GA, Pittman K, Boykin C, Herring LE, Wilkerson EM, et al. Therapeutic Effect of Y-27632 on Tumorigenesis and Cisplatin-Induced Peripheral Sensory Loss through RhoA-NF-κB. Mol Cancer Res. 2019;17(9):1910. https://doi.org/10.1158/1541-7786.MCR-19-0024

Aguilar BJ, Zhao Y, Zhou H, Huo S, Chen YH, Lu Q. Inhibition of Cdc42-intersectin interaction by small molecule ZCL367 impedes cancer cell cycle progression, proliferation, migration, and tumor growth. Cancer Biol Ther. 2019;20(6):740. https://doi.org/10.1080/15384047.2018.1564559.

Do K, Laing BT, Landry T, Bunner W, Mersaud N, Matsubara T, et al. The effects of exercise on hypothalamic neurodegeneration of Alzheimer's disease mouse model. PLoS One. 2018;13(1):e0190205. https://doi.org/10.1371/journal.pone.0190205.

Aguilar BJ, Zhou H, Lu Q. Cdc42 Signaling Pathway Inhibition as a Therapeutic Target in Ras- Related Cancers. Curr Med Chem. 2017;24(32):3485.

Aguilar BJ, Zhu Y, Lu Q. Rho GTPases as therapeutic targets in Alzheimer's disease. Alzheimers Res Ther. 2017;9(1):97. https://doi.org/10.1186/s13195-017-0320-4.

Lu Q, Aguilar BJ, Li M, Jiang Y, Chen YH. Genetic alterations of δ-catenin/NPRAP/Neurojungin (CTNND2): functional implications in complex human diseases. Hum Genet. 2016;135(10):1107.

Haskins M, Jones TE, Lu Q, Bareiss SK. Early alterations in blood and brain RANTES and MCP-1 expression and the effect of exercise frequency in the 3xTg-AD mouse model of Alzheimer's disease. Neurosci Lett. 2016;610:165. https://doi.org/10.1016/j.neulet.2015.11.002.

Y Z, M Z, Q L, H Z, . Target protein-protein Interactions in Rho GTPase regulation using small molecules. Science. 2016;351(6278).
Nopparat J, Zhang J, Lu JP, Chen YH, Zheng D, Neufer PD, et al. δ-Catenin, a Wnt/β-catenin modulator, reveals inducible mutagenesis promoting cancer cell survival adaptation and metabolic reprogramming. Oncogene. 2015;34(12):1542.

Friesland A, Weng Z, Duenas M, Massa SM, Longo FM, Lu Q. Amelioration of cisplatin-induced experimental peripheral neuropathy by a small molecule targeting p75 NTR. Neurotoxicology. 2014;45:81. https://doi.org/10.1016/j.neuro.2014.09.005.

Vezzu DA, Lu Q, Chen YH, Huo S. Cytotoxicity of cyclometalated platinum complexes based on tridentate NCN and CNN-coordinating ligands: remarkable coordination dependence. J Inorg Biochem. 2014;134:49. https://doi.org/10.1016/j.jinorgbio.2014.01.021.

Friesland A, Zhao Y, Chen YH, Wang L, Zhou H, Lu Q. Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility. Proc Natl Acad Sci U S A. 2013;110(4):1261.

Boykin C, Zhang G, Chen YH, Zhang RW, Fan XE, Yang WM, et al. Cucurbitacin IIa: a novel class of anti-cancer drug inducing non-reversible actin aggregation and inhibiting survivin independent of JAK2/STAT3 phosphorylation. Br J Cancer. 2011;104(5):781.

Zhang G, Lai BB, Zhou YY, Chen BA, Wang XM, Lu Q, et al. Fe3O4 nanoparticles with daunorubicin induce apoptosis through caspase 8-PARP pathway and inhibit K562 leukemia cell-induced tumor growth in vivo. Nanomedicine. 2011;7(5):595.

Zhang G, Ding L, Renegar R, Wang X, Lu Q, Huo S, et al. Hydroxycamptothecin-loaded Fe3O4 nanoparticles induce human lung cancer cell apoptosis through caspase-8 pathway activation and disrupt tight junctions. Cancer Sci. 2011;102(6):1216. 

James SE, Dunham M, Carrion-Jones M, Murashov A, Lu Q. Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin. Neurotoxicology. 2010;31(2):188. 

Zhang J, Lu JP, Suter DM, Krause KH, Fini ME, Chen B, et al. Isoform- and dose-sensitive feedback interactions between paired box 6 gene and delta-catenin in cell differentiation and death. Exp Cell Res. 2010;316(6):1070. 

Bareiss S, Kim K, Lu Q. Delta-catenin/NPRAP: A new member of the glycogen synthase kinase-3beta signaling complex that promotes beta-catenin turnover in neurons. J Neurosci Res. 2010;88(11):2350. 

Lu Q, Ding K, Frosch MP, Jones S, Wolfe M, Xia W, et al. Alzheimer's disease-linked presenilin mutation (PS1M146L) induces filamin expression and γ-secretase independent redistribution. J Alzheimers Dis. 2010;22(1):235.