Pathology and Microbiology Graduate Program
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.
Education and Training
- M.Sc., Banaras Hindu University, Varanasi, India, 1987
- Ph.D., Banaras Hindu University, Varanasi, India, 1991
- Postdoctoral fellow, M.D. Anderson Cancer Center, Houston, TX
1991-1995.
Awards and Recognition
Editorial Board: Angiogenesis
ISCA Young Scientist Award by Indian Science Congress Association, 1991
Young Investigator Award, International Society of Differentiation
(I.S.D.), 1994
U.S. National Academy of Sciences/UICC Young Investigator Award, 1998
FIRST Award from National Institutes of Health, 1998.
Teaching
Immunology, Tumor progression and metastasis; Immunology Interest Group
Recent Publications
Patel, P.S., Varney
M.L., Dave B.J., and Singh R.K.. Regulation of constitutive and
induced-NF-kB activation in malignant melanoma cells by capsaicin
modulates interleukin-8 production and cell proliferation. J.
Interferon and Cytokine Res., 22:427-435, 2002.
Patel., P.S., Varney
M.L., Yang, S., Li, A., and Singh R.K.. Capsaicin regulates
vascular endothelial cell growth factor expression by modulation of
hypoxia inducing factor-1in human malignant melanoma cells. Journal
of Cancer Research and Clinical Oncology, 128:461-468,2002.
Li A, Dubey S,
Varney ML, and Singh RK. Interleukin-8 induced proliferation,
survival and MMPs production in CXCR1 and CXCR2 expressing human umbilical
vein endothelial cells.
Microvascular Research, 64:476-481, 2002.
Varney ML, Olsen KJ,
Mosley RL, Bucana CD, Talmadge JE and Singh RK.
Monocyte/macrophage recruitment, activation and differentiation modulate
interleukin-8 production: a paracrine role of tumor-associated macrophages
in tumor angiogenesis. In Vivo, 16:471-478, 2002.
Li A, Dubey S,
Varney ML, Dave BJ, and Singh RK.
Interleukin-8 directly enhanced
endothelial cell survival, proliferation, and matrix metalloproteinases
production and regulates angiogenesis. Journal of Immunology,
170:369-3376, 2003.
Rao VH, Lees GE,
Kashtan CE, Nemori R, Singh RK, Meehan DT, Rodgers K,
Berridge B and Cosgrove D. Increased expression of MMP-2 (Type IV
collagenase/gelatibnases) and MT1-MMP in canine X-linked Alport Syndrome
(XLAS). Kidney International, 63:1736-1748, 2003.
Robinson SN, Pisarev
VM, Chavez JM, Singh RK, and Talmadge JE. Use of metalloproteinase
(MMP)-9 knock-out mice demonstrate that MMP-9 activity is not
absolutelyrequired for G-CSF or Flt-3 ligand induced hematopoitic
progenitor cell mobilization or engraftment. Stem Cells, 21:417-427,
2003.
Varney ML, Li A.,
Dave BJ, Johansson SL, Bucana CB and Singh RK. Expression of CXCR1
and CXCR2 receptors in malignant melanoma with different metastatic
potential and their role in interleukin-8 (CXCL-8)-mediated modulation of
metastatic phenotype. Clinical and Experimental Metastasis,
20:723-731, 2003.
Sadanandam, A,
Varney ML, and Singh R.K. High-Throughput Computational and
Experimental Biology Strategy in Identifying Tumor Expressing CAMs.
Computational Systems Bioinformatics Conference, CSB2004, IEEE Computer
Society, p 450 - 451, 2004.
Huang X, Ali H,
Sadanandam A, and Singh RK. SRPVS: A New Motif Searching Algorithm
for Protein Analysis. Computational Systems Bioinformatics, CSB2004,
IEEE Computer Society, p 674-675, 2004.
Singh RK
and Talmadge JE. The Evolution of Diversity within Tumors and Metastases.
In: Fundamental Aspects of Cancer, vol. 1 CAGP series. Editor: RH
Goldfarb. Kluwer Academic Publishers. The Netherlands, 2004.
Li A, Varney ML, and
Singh RK. Constitutive
expression of growth regulated oncogene-alpha (gro-a/CXCL1) in
human colon carcinoma cells with different metastatic potential and its
role in regulating their growth and invasive potential. Clinical and
Experimental Metastasis,
21:571-579, 2004.
Sang H, Pisarev VM,
Chavez J, Robinson SR, Guo Y, Hatcher L, Munger C, Solheim JC, Singh RK,
and Talmadge JE. Murine Mammary
adenocarcinoma cells transfected with p53 and/or FLT3L induce anti-tumor
response. Cancer Gene Therapy, 12:427-437, 2005.
Rao VH, Lees GE,
Kashtan CE, Delimont DC, Singh RK, Meehan DT, Berridge BR, Cosgrove
D. Potential role of stromolysin-1 (MMP3) and matrilysin (MMP7) in renal
pathogenesis associated with Canine X-linked alport syndrome (XLAS).
Pediatrics Nephrology, 20: 732-739, 2005.
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, 2005 (In Press).
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, 2005 (In Press).
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, (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, 2005 (In Press).
Varney ML and Singh RK. Inflammation and Cancer. (review)
Indian Journal of Experimental Medicine. 2005 (In Press).
Futakuchi M, Talmadge, JE and Singh RK. Synergy between tumor
immunotherapy and anti-angiogenic therapy. (Review).
Archivum Immunologiae et Therapiae Experimentalis, 2005 (In Press).
Updated 01/07/06
