Pathology and Microbiology

Rakesh K. Singh, Ph.D.

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ACADEMIC DEGREES:

1991	Ph.D. Department of Zoology, Faculty of Science, B. H.U., India
1991 - 1994	Postdoctoral Fellow Department of Cell Biology The University of Texas M.D. Anderson Cancer Center, Houston TX

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Contact Name: Rakesh K. Singh, Ph.D.
Phone Number: 402 559 9949
e-mail address: rsingh@unmc.edu

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• GRANT SUPPORT (last 3 years):

Source and identifying No.:  NIH, CA72781
Principal investigator:  Rakesh K. Singh
Title:  Molecular Regulation of Human Melanoma Metastasis
Goals: To determine the role of IL-8, a multifunctional cytokine in melanoma growth and metastasis.

Source and identifying No.: Nebraska Research Initiative 
Project investigator: Rakesh K. Singh
Title:  Program in Molecular Therapeutics.
Goals: To develop molecular therapeutics program at UNMC.

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• PUBLICATIONS (last 3-5 years):

Lynch CC, Hikosaka A., Kawai N., Singh RK, Vargo-Gogola C., Fingleton F, Shirai T, Matrisian LM, Futakuchi M. Matrix metalloproteinase-7 (MMP-7) promotes prostate cancer induced osteolysis via the solubilization of receptor activator of nuclear kB ligand (RANKL). Cancer Cell, 7:485-496, 2005.

Li A, Dave BJ, Varney ML, and Singh RK. Autocrine role of Interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production: Mechanism for interleukin-8-mediated angiogenesis, Angiogenesis, 8:63-71, 2005.

Varney ML, Johansson SL, and Singh RK. Tumor-associated macrophage infiltration, neovascularization and aggressiveness in malignant melanoma: role of monocyte chemotactic protein-1 and vascular endothelial growth factor-A. Melanoma Research, 15:417-425, 2005.

Zhengtang C, Varney ML, Backora M., Cowan K, Solheim JC, Talmadge JE and Singh RK.  Down-regulation of VEGF-C expression using small interfering RNA vectors in mammary tumors inhibits tumor lymphangiogenesis and spontaneous metastasis and enhanced survival.  Cancer Res., 65:9004-9011, 2005.

Varney ML, Johansson SL, and Singh RK. Distinct expression of CXCL8 and its receptors CXCR1 and CXCR2 and their association with vessel density and aggressiveness in malignant melanoma. American J. Clinical Pathology, 125:1-8, 2006.

Varney ML, Olsen KJ, Mosley RL, and Singh RK. Paracrine Regulation of Vascular Endothelial Growth Factor-A Expression during Macrophage-Melanoma Cell interaction:  Role of Monocyte Chemotactic Protein-1 and Macrophage Colony Stimulating Factor.  J. Interferon and Cytokine Research, 25: 674-683, 2005.

Huang X, Ali H, Sadanandam A, and Singh RK. Protein motif searching through similar enriched Parikh vector identification.  Bioinformatics and Bioengineering, BIBE05, IEEE Computer Society,(In Press).

Turnquist HR, Ashour AE, Hollingsworth MA, Singh RK, Talmadge JE and Solhein JC.  CCL21 Induces Extensive Intratumoral Immune Cell Infiltration and Specific Anti-Tumor Cellular Immunity.  Cancer Immunology Immunotherapy (In Press)

Talmadge, JE Singh RK and Solheim J.  Activity of Cytokine Mediators of Dendritic Cell Chemotaxis and Expansion.  In: Recent Research Developments in Cancer, Transworld Research Network, (In Press)

Varney ML and Singh RK.  Inflammation and Cancer.  (review)  Indian Journal of Experimental Medicine. (In Press)

Futakuchi M, Talmadge, JE and Singh RK.  Synergy between tumor immunotherapy and anti-angiogenic therapy.  (Review).  Archivum Immunologiae et Therapiae Experimentalis,  (In Press)

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• PREVIOUS GRADUATE STUDENTS/POST-DOCTORAL FELLOWS (present location):

Graduate Students:	Michelle L. Varney, 2000-03 Anguraj Sadanandam, 2003-
Visiting Scientist:	Shillin Yang, M.D., 2000 - 2002 Current position: Clinical Scientist Shanghai International Joint Cancer Institute The Second Military Medical Academy Shanghai, PR China Prabhudas Patel, Ph.D., 1999 - 2000 Current position: Director and Sr. Scientific Officer Biochemistry Division The Gujarat Cancer & Research Institute Asarwa, Ahmedabad, India Zhengtang Chen, M.D., Ph.D., 2002 - 2003 Professor and Chief Physician Head of Cancer Center of PLA 2nd Teaching Hospital, Third Military Medical University                  Chongqing, PR China
Postdoctoral Fellow:	Mitsuru Futakuchi, M.D., Ph.D., 2003 - 2005 Current Position: Associate Professor Department of experimental Patholgy and Tumor Biology, Graduate School of Medical Sciences Nagoya City University 1 Kawasumi, Mizuho-cho, Mizuho-ku Nagoya 467-8601 Japan Aihua Li, M.D., Ph.D., 2000 - 2002 Current position: Instructor Department of Molecular Medicine University of California at Irvine Irvine, CA

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• CURRENT RESEARCH PROJECTS:

The overall goal of our research is to define the mechanism(s) that regulate the process of metastasis. We hypothesize that metastasis is a highly selective process that is regulated by interrelated mechanisms whose outcome is dependent upon both the intrinsic properties of tumor cells and the host response. Using human tumors xenografted in nude mice and murine tumor models, these studies have demonstrated the role of host-derived factors in regulating angiogenesis, resulting in site-specific expression of angiogenic factors, including basic fibroblast growth factor (bFGF), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and metastasis. Further characterizations of the cellular and molecular mechanisms underlying these processes are currently ongoing in our laboratory. In addition, we are investigating the mechanism(s) of organ-specific metastasis.  Recent reports suggest specific organ tissues carry unique marker molecules accessible to circulating cells. We have identified the molecule(s) expressed in organ tissues, which might be important to organ-specific metastasis using phage display libraries.  Further characterization of organ-specific signature molecules will be useful in designing novel, highly targeted therapeutic approaches against organ-specific metastasis. In addition, our current research activities have also been focused on: 1) designing the strategies for inhibiting tumor-induced angiogenesis and activating anti-tumor immunity; two non-cross-resistant therapeutic approaches with the potential for synergizing the outcome of conventional therapeutic approaches; and 2) understanding the role of tumor-stromal interaction in tumor progression and metastasis.

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• SPECIALIZED LABORATORY/CLINICAL RESEARCH RESOURCES:

Non-radioactive in-situ hybridization for mRNA analysis.
Syngenic and xenogenic model for solid tumor progression and metastasis.

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