Ramesh Ganju, PhD
Professor and Vice Chair
Phone:
Gina Alderson:
E-mail:
Mailing Address:
810 Biomedical Research Tower
460 W. 12th Ave
Columbus, OH 43210
Biosketch
The major focus of my laboratory is to elucidate mechanisms that regulate tumor growth and metastasis. We are also developing immune-based therapies against solid tumors. In my earlier publications, I developed a strategy for the production of small, soluble, single-chain T-cell receptors (scTCR) fragment that carry an intact TCR antigen combining site. I have shown that the soluble proteins have antigen-binding properties equivalent to those of intact TCR. These results demonstrated the feasibility of obtaining TCR fragments endowed with antigen-combining properties by protein engineering in E- Coli. Further taking advantage of scTCR methodology, I have identified putative antigen-containing residues in the antigen-combining site of TCR molecule. I have shown that the antibodies in TCR are similar both in their overall architecture and in the chemical details of specific antigen recognition. I have also identified novel components such as RAFTK downstream of TCR signaling pathways. I have shown that RAFTK participates in TCR signaling and may act to link signals from the cell surface to the cytoskeleton and thereby affect the host immune response. I have also analyzed the role of membrane tyrosine phosphatase CD45 which regulates antigen receptor signaling in CXCR4-mediated chemotaxis and mitogen-activated protein kinase (MAPK) activation in T cells. I have shown that CD45 differentially regulates CXCR4-mediated chemotactic activity and MAPK activation by modulating the activities of focal addition components and the downstream effectors of the TCR. I have also identified novel signaling pathways that regulate tumor growth, chemo-invasion and metastasis of tumor cells especially breast cancer. I was the first to identify chemokine receptor CXCR4-inducing signaling circuits that regulate breast cancer cell mortality and invasion. I have discovered several novel biomarkers and signaling molecules that regulate growth and metastasis of triple-negative breast cancer (TNBC) including fatty acid binding protein 5 and TRPV2. My laboratory has also generated novel transgenic and knockout mouse models to understand mechanisms that regulate breast tumor growth and metastasis especially the role of tumor microenvironment. I have identified distinct signaling pathways that mediate cell growth, migration and transcriptional activation. I have also analyzed the role of tumor stroma in modulating tumor growth and metastasis and shown that interaction between epithelial cells and cells present in tumor microenvironment especially tumor associated macrophages play an important role in regulating growth and metastasis in breast cancer. I have analyzed the role of pro-inflammatory molecules such as receptor for advanced glycosylation end product (RAGE) and S100A7 in breast growth and metastasis. I also employed a powerful new model system to demonstrate that S100A7 enhances breast tumor growth and metastasis by activating pro-inflammatory and metastatic pathways. I have also analyzed the tumor suppressive effects of anti-inflammatory molecules Slit-2. Slit-2 has been shown to bind to ROBO receptors. I have elucidated Slit-2 mediated mechanisms that regulate inflammation tumor growth and metastasis in Breast Cancer. My laboratory is also identifying small molecular weight anti-inflammatory molecules that has potential to be used as drugs to block breast and lung cancer growth and metastasis. In this regard, I have shown that small molecular weight synthetic cannabinoids that binds to cannabinoid receptors CB1/CB2 inhibits lung and breast tumor growth and metastasis through novel signaling mechanisms. In addition, I have shown that cannabidiol, non-psychotropic cannabinoid compound inhibits breast tumor growth through novel mechanisms by inhibiting EGF/EGFR signaling and modulating the tumor microenvironment. I have been NIH funded continually for the last 22 years and have also received funding from Department of Defense and private foundations. I have mentored several graduate students, postdoctoral fellows, undergraduate, high school and medical students. As a PI or Co-I, I have successfully collaborated with other researchers and produced several peer review publications from each project.
Academic and Medical Appointments
2007-Present Scott Endowed Professor,Vice Chair of Experimental Pathology, Department of Pathology, The Ohio State University, Columbus, Ohio
1997-2007 Associate/Assistant Professor of Medicine, Harvard Medical School, Boston, MA
1992-1997 Instructor in Medicine, Harvard Medical School, Boston, MA
Education and Training
1989-1992 Research Fellow in Pathology and Laboratory of Immunobiology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
1987-1989 Postdoctoral Fellow/Project Investigator, Department of Medical Oncology, M.D. Anderson Cancer Center, Houston, TX
1980-1985 Ph.D., Indian Institute of Science, Bangalore, India
1979-1980 M.S., Panjab University, Chandigarh, India
1976-1979 B.S., Panjab University, Chandigarh, India
Selected Publications
- Sarkar C, Ganju RK, Pompili VJ, Chakroborty D. Enhanced peripheral dopamine impairs post-ischemic healing by suppressing angiotensin receptor type 1 expression in endothelial cells and inhibiting angiogenesis. Angiogenesis. 2017 Feb;20(1):97-107. doi: 10.1007/s10456-016-9531-8. PMID: 27853962.
- Elbaz M, Ahirwar D, Xiaoli Z, Zhou X, Lustberg M, Nasser MW, Shilo K, Ganju RK. TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer. Oncotarget. 2016 May 27. doi: 10.18632/oncotarget.9663 [Epub ahead of print]. PMID: 27248470.
- Elbaz M, Ahirwar DK, Ravi J, Nasser MW, Ganju RK. Novel role of CB2R in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer. Oncotarget. April 2016 (In Press)
- Zhao H, Ahirwar DK, Oghumu S, Wilkie T, Powell CA, Nasser MW, Satoskar AR, Li DY, Ganju RK. Endothelial Robo4 suppresses breast cancer growth and metastasis through regulation of tumor angiogenesis. Mol Oncol. 2016:Feb;10(2):278-81.
- Ravi J, Elbaz M, Wani NA, Nasser MW, Ganju RK. Cannabinoid receptor-2 agonist inhibits macrophage induced EMT in non-small cell lung cancer by downregulation of EGFR pathway. Mol Carcinog. 2016 Jan 6 (In Press). PMID: 26741322
- Powell C, Nasser M, Zhao H, Wochna JC, Zhang X, Shilo K, Shapiro C, Ganju RK. Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer cells through enhanced epidermal growth factor receptor stability. Oncotarget. 2015 Mar 20;6(8):6373-85. PMID: 25779666
- Zhao H, Wilkie T, Deol Y, Sneh A, Ganju A, Basree M, Nasser MW, Ganju RK. miR-29b defines the pro-/anti-proliferative effects of S100A7 in breast cancer. Molecular Cancer. 2015 Jan 27;14(1):11. PMID: 25622979
- Nasser MW, Wani NA, Ahirwar DK, Powell, CA, Ravi, J, Elbaz, M, Zhao, H, Padilla, L, Zhang, X, Shilo, K, Ostrowski, M, Shapiro, C, Carson, Carson, WE 3rd, Ganju RK. RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment. Cancer Research 2015 Mar 15;75(6):974-85. PMID: 25572331.
- Ravi J, Sneh A, Shilo K, Nasser MW, Ganju RK. FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway. Oncotarget. 2014 5(9):2475-86. PMID: 24811863
- Nasser MW, Qamri Z, Deol YS, Shilo K, Leone G, Bai X-F, Zou X, Wolf R, Yuspa S, Ganju RK. S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways. Cancer Res 2012;1;72(3):604-15. PMID:22158945
- Deol YS, Nasser MW, Yu L, Zou X, Ganju RK. Tumor-suppressive effects of psoriasin (S100A7) are mediated through β-catenin/TCF4 protein pathway in estrogen receptor positive breast cancer cells. J Biol Chem 2011; 286(52):44845-54. PMID:22016394.
- 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.
- Prasad A and Ganju RK. Slit-2 induces a tumor-suppressive effect by regulating beta-catenin in breast cancer cells. J Biol Chem. 2008. 283(39):26624-33.
- 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.
- Prasad A, Wu J and Ganju RK. “Slit-2/Robo-1 modulates the CXCL12/CXCR4-induced chemotaxis of T cells”. J Leukocyte Biol. 2007; 82(3):465-76 Selected as Pivotal Advance.
- Prasad A, Fernandis AZ, Rao Y, Ganju RK. Slit protein-mediated inhibition of CXCR4-induced chemotactic and chemoinvasive signaling pathways in breast cancer cells. J Biol Chem. 2004; 279:9115-9124.
- Fernandis AZ, Prasad A, Band H, Klosel H, Ganju RK. Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells. Oncogene. 2004; 23:157-167
- Fernandis AZ, Cherla RP, Ganju RK. Differential regulation of CXCR4-mediated T-cell chemotaxis and MAP kinase activation by the membrane tyrosine phosphatase, CD45. J Biol Chem. 2003; 278:9536-9543
- Ganju RK, Dutt P, Wu L, Newman W, Avraham H, Avraham S, Groopman JE. Beta-chemokine receptor CCR5 signals via the novel tyrosine kinase RAFTK. Blood. 1998; 91:791-797.
- Ganju RK, Hatch WC, Avraham H, Ona M, Druker B, Avraham S, Groopman JE. RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T-lymphocytes. J Exp Med. 1997; 185:1055-1063.