Wu Y, Jin Y, Feng X, Wu Z, Hankey W, Paisie C, Liu F, Barsky SH, Shang W, Ganju R, Zou X. The dietary phytochemical indole-3-carbinol induces Cdc25A degradation and inhibits the growth of human breast cancer cells. Cancer Prevention Research. 2010. (In press)
Tamama K, Kawasaki H, Guan J, Ganju RK, Sen CK. Differential roles of hypoxia inducible factor subunits in multipotential stromal cells under hypoxic condition. Journal of Cellular Biochemistry. 2010 (In Press).
Preet A, Qamri Z, Nasser MW, Prasad A, Shilo K, Zou X, Groopman J, Ganju RK. Cannabinoid Receptors, CB1 and CB2, as Novel Targets for Inhibition of Non-Small Cell Lung Cancer Growth and Metastasis. Cancer Prevention Research 2010 (In Press). PMID: 21097714
Qamri Z, Preet A, Nasser MW, Bass CE, Leone G, Barsky SH, Ganju RK. Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol Cancer Ther. 2009;8(11):3117-29. PMID: 19887554
Anand AR, Prasad A, Bradley RR, Deol YS, Nagaraja T, Ren X, Terwilliger EF, Ganju RK. HIV-gp120-induced migration of dendritic cells is regulated by a novel kinase cascade involving Pyk2, p38 MAP kinase, and LSP1. Blood. 2009;114(17):3588-600. PMID: 19700666
Anand AR, Bradley R, Ganju RK. LPS-induced MCP-1 expression in human microvascular endothelial cells is mediated by the tyrosine kinase, Pyk2 via the p38 MAPK/NF-kappaB-dependent pathway. Mol Immunol. 2009. 46:962-968. PMID: 18954908
Prasad A, Paruchuri V, Preet A, Latif F, Ganju RK. Slit-2 induces a tumor suppressive effect by regulating beta -catenin in breast cancer cells. J Biol Chem. 2008; 283:26624
Preet A, Groopman JE and Ganju RK. Δ9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in-vitro as well as its growth and metastasis in-vivo. Oncogene. 2008; 27:339.
Anand AR, Cucchiarini M, Terwilliger EF and Ganju RK. The tyrosine kinase Pyk2 mediates lipopolysaccharide-induced Il-8 expression in human endothelial cells. J. Immunol. 2008; 180(8):5636.
Paruchuri P, Prasad P, McHugh K, Polyak K, and Ganju RK. S100A7-downregulation Inhibits EGFR-Induced Signaling in Breast Cancer Cells and Blocks Osteoclast Formation. PLoS ONE. 2008; 3 (3):e1741.
Gupta1 AT. Guerin-Peyrou G, Sharma GG, Park C, Agarwal M, Ganju RK , Choi1 K, Sukumar S, Pandita R, Ludwig and Pandita TK: Mammalian Ortholog of Drosophila MOF that Acetylates Histone H4 Lysine16 is Essential for Embryogenesis and Oncogenesis. Mol Cell Biol. 2008; 28(1):397-409.
Prasad A, Wu J and Ganju RK. “Slit-2/Robo-1 modulates the CXCL12/CXCR4-induced chemotaxis of T cells”. J Leukoc Biol. 2007; 82(3):465-76.
Balasubramanian A, Koziel M, Groopman JE and Ganju RK. Signal transducer and activator of transcription factor 1 mediates apoptosis induced by hepatitis C virus and HIV envelope proteins in hepatocytes. J Infect Dis. 2006; 194:670-81.
Ghosh S, Preet A, Groopman JE, Ganju RK. Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes. Mol Immunol. 2006; 43:2169-79.
Lane HC, Anand AR, Ganju RK. Cbl and Akt regulate CXCL8-induced and CXCR1- and CXCR2-mediated chemotaxis. Int Immunol. 2006:18:1315-25.
Anand AR and Ganju RK. HIV gp120-mediated apoptosis of T-cells is regulated by membrane tyrosine phosphotase CD45. J Biol Chem. 2006 5;281(18):12289-99.
The primary focus of our laboratory is to delineate the role of chemokine receptors (especially CXCR4) in progression and metastasis of breast cancer. We are also analyzing the molecular mechanism of CXCR4-mediated pathogenesis during HIV and HCV/HIV Co- infection. In addition, we are characterizing the cross-talk between Slit/Robo and chemokine receptor pathways as a novel target for combating breast cancer metastasis and HIV infection.
Role of Chemokines in Breast Cancer Progression and Metastasis:
Our laboratory is analyzing the role of the chemokine receptor CXCR4 in breast cancer metastasis and its inhibition by a novel Slit/Robo complex. It has recently been shown that the chemokine receptor CXCR4 and its ligand CXCL12 play a critical role in breast cancer metastasis. We have identified novel signaling pathways mediated by CXCR4 that regulate the CXCL12-induced chemotaxis, chemoinvasion, and adhesion of breast cancer cells. In this context, we have shown that focal adhesion kinases, Cbl, and tyrosine phosphatases play an important role in breast cancer cell chemotaxis/chemoinvasion. We are also developing innovative strategies to block the CXCR4-mediated metastasis of breast cancer cells. In this regard, we have shown that the Slit protein, which binds to the Robo receptor, blocks the CXCR4-induced chemotaxis, chemoinvasion, and adhesion of breast cancer cells. Further analysis of Slit-mediated anti-tumorigenic and metastatic mechanisms revealed that Slit downmodulates the expression of psoriasin. Psoriasin is among the most highly expressed genes in breast cancer patients with pre-invasive ductal carcinoma in situ. Furthermore, a poor prognosis is associated with the persistent expression of psoriasin in invasive carcinoma. Our laboratory has shown that various growth factors that stimulate breast cancer growth such as EGF and IGF also regulate psoriasin expression. We have also shown that psoriasin may regulate osteoclast formation as well as breast cancer metastasis to bone. We are further elucidating the signaling mechanism through which psoriasin may modulate the growth and metastasis of breast cancer.
Our laboratory is also identifying small molecular weight molecules that have potential to be used as drugs to block metastasis. In this regard we have shown that cannabinoids, which are small molecular weight molecules, inhibit the CXCR4-mediated functions of immune cells. In preliminary studies, we have further found that these compounds, which mediate their effects through the cannabinoid receptors CB1 and CB2, can block the growth and chemotaxis of lung cancer cell lines and breast cancer cell lines under in vitro and in-vivo conditions. We are further analyzing the cannabinoid-mediated molecular mechanism of inhibition of growth and metastasis.
Role of Chemokines in HIV and HCV/HIV Co-infection.
Worldwide, about 40 million people are infected with human immunodeficiency virus type 1 (HIV-1). The depletion of CD4+ T lymphocytes is a central pathogenic feature of (HIV-1) infection and is largely responsible for the profound immunodeficiency characteristic of the late stages of HIV disease. Our laboratory is analyzing the molecular mechanism of T-cell loss during HIV infection. We have shown that cross-talk between the chemokine receptor CXCR4/CCR5 and immune signaling components modulates the activities of novel apoptotic effector molecules. Our laboratory is further defining and elucidating the HIV-induced apoptotic signaling mechanism in primary cells isolated from healthy and HIV-infected individuals, and determining how these signaling cascades could be altered to prevent the loss of immune cells during HIV infection. We are also exploring the effects of various molecules that block CXCR4 function on HIV pathogenesis. In this regard, we have shown that the novel Slit/Robo complex blocks CXCR4-mediated functional effects.Our laboratory is also elucidating the molecular mechanism of hepatic injury in HCV/HIV co-infection. Hepatitis C virus (HCV) infects approximately 40% of patients with human immunodeficiency virus (HIV). Worldwide, about 200 million people are infected with HCV and about 40 million are infected with HIV. HCV/HIV co-infected patients have progressive liver disease that leads to cirrhosis and death. However, the molecular mechanism of enhanced cirrhosis and inflammation observed in these patients is not known yet. Our laboratory has observed that HCV and HIV envelope proteins induce apoptosis and inflammatory responses in hepatocytes via a novel “innocent bystander” mechanism. Further elucidation of signaling mechanisms revealed that the HCV/HIV envelope proteins cooperatively induce hepatocytic apoptosis by activating a novel downstream STAT1 signaling pathway. We are further elucidating the pathophysiology of liver disease caused by HCV/HIV co-infection that may help in the development of novel therapeutic strategies for HCV/HIV infection.
Appakkudal Anand, PhD
Mohd Nasser, PhD
Senior Research Associate
Zahida Qamri, PhD
Post-doctoral research fellow
Yadwinder Deol, MS
Graduate Research Associate
Xiaoyi Mi, MD, PhD
Visiting Research Scholar
Graduate Student (Rotation)