Shrikant Anant, Ph.D.

Professor
Kansas Mason Professor for Cancer Research
Associate Director for Prevention and Cancer Control
Associate Dean for Research
The Tom and Teresa Walsh Professorship in Cancer Prevention and Survivorship
University of Illinois at Chicago, 1993


Research Focus

Posttranscriptional gene regulation in inflammation and cancer, cancer stem cells and chemoprevention

Research Overview

Research in the laboratory is focused on various aspects of cancer biology at the molecular level. Specific research areas include: (a) Regulation of gene expression at the levels of mRNA stability and translation, (b) Cancer Stem Cells, and (c) mechanism(s) of chemoprevention by dietary factors and its novel derivatives.

Regulation of Gene Expression: A major focus of the laboratory has been in the role of RNA binding proteins in posttranscriptional control of gene expression. We have identified two specific RNA binding proteins, CUGBP2 and RBM3. Both protein interact with AU-rich sequences in the 3'untranslated region of rapidly degraded RNAs. While CUGBP2 is a translation suppressor, RBM3 is a translation enhancer. We are currently characterizing the mechanisms by which these proteins interact with the mRNA to regulate its stability and translation. We are currently also determining the effect of these RNA binding proteins in induced pluripotency.

Cancer Stem Cells: Stem cell research provides a foundation for therapeutic advancement in oncology. Currently, identification and characterization of reliable stem cell markers is the top priority in this field. We have characterized multiple markers and have also identified protooncogene-induced cancer stem cells (PICSCs), a unique resource to study the biology and therapeutic targeting of specific cancer-initiating cells within the tumor. We are currently determining the microRNA profiles and the signaling mechanisms that regulate their expression in these cells.

Dietary Chemoprevention and Novel Therapeutics: Another focus of the laboratory is to determine mechanisms by which progression of a normal cell to a cancer cell can be prevented. We are particularly interested in determining mechanisms by which dietary phytochemicals such as curcumin and marmelin regulate gene expression in colorectal, breast and pancreatic tumors. In addition, we have developed novel therapeutic agents based natural dietary compounds and are testing them for efficacy against various cancer cells. We are currently testing them in in vitro and in vivo models to determine their efficacy in inhibiting growth of tumor cell by themselves and to sensitize the cancer cells to radiation and chemotherapy. Our current research includes the molecular analysis of cancer cells following treatment with these agents.

Representative Publications

Mukhopadhyay, D., Houchen, C., Kennedy, S., Dieckgraefe, B.K., and Anant, S. 2003. Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2. Mol. Cell 11:113-126.

Murmu, N., Jung, J., Mukhopadhyay, D., Houchen, C.W., Riehl, T.E., Stenson, W.F., Morrison, A.R, Arumugam, T., Dieckgraefe, B.K., and Anant, S. 2004. Dynamic antagonism between RNA binding protein CUGBP2 and cyclooxygenase-2 in intestinal epithelial radiation damage. Proc Natl Acad Sci USA 101: 13873-13878.

Anant, S., Murmu, N., Houchen, C. W., Mukhopadhyay, D., Riehl, T.E., Young, S.G., Morrison, A.R, Stenson, W.F., Davidson, N.O. 2004. Apobec-1 protects intestine from radiation injury through posttranscriptional regulation of cyclooxygenase-2 expression. Gastroenterology, 124: 1139-1149, Editorial comment on page 1259.

Sureban, S.M., Subramaniam, D, Rajendran, P., Dieckgraefe, B.K., Houchen, C.W., and Anant, S. 2006. Therapeutic effects of Phyllanthus species: anti-proliferative activity in HepG2 a hepatocellular carcinoma cells, Submitted, Under Consideration, Amer J Pharm Toxicol 1(4): 65-71.

Weir, N.M., Selvendiran, K., Kutala, V.K., Tong, L., Vishwanath, S., Rajaram, M., Tridandapani, S., Anant, S., Kuppusamy, P. 2007. Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biology and Therapy 6(2):178-184.

Sureban, S.M., Murmu, N., Rodriguez, P., May, R., Dieckgraefe, B.K., Houchen, C.W., and Anant, S. 2007. RNA binding proteins HuR and CUGBP2 have antagonistic properties in regulating stability and translation of cyclooxygenase-2 mRNA. Gastroenterology 32(3):1055-1065.

Sureban, S.M., Ramalingam, S., Natarjan, G., Subramaniam, D, Morrison, A., Bishnupuri, K.S., Dieckgraefe, B.K., Houchen, C.W., and Anant, S. 2008. RNA translation factor RBM3, a protooncogene essential to overcome mitotic catastrophe. Oncogene. 27(33):4544-4556

Sureban, S.M., May, R., Ramalingam, S., Subramaniam, D., Natarajan, G., Anant, S., Houchen, C.W. 2009. Selective Blockade of DCAMKL-1 Results in Tumor Growth Arrest by a Let-7a MicroRNA-Dependent Mechanism. Gastroenterology. 137(2):649-659.

May, R., Sureban, S.M., Hoang, N., Riehl, T.E., Lightfoot, S.A., Ramanujam, R., Wyche, J.H., Anant, S., and Houchen, C.W. 2009.  DCAMKL-1 and LGR5 Mark Quiescent and Cycling Intestinal Stem Cells Respectively. Stem Cells. 27:2571-2579.

Anant, S. and Houchen, C.W. 2009. HuR and TTP: two RNA binding proteins that deliver message from the 3' end. Gastroenterology. 136(5):1495-8.

Pantazis,, P., Varman, A., Simpson-Durand, C., Thorpe, J., Ramalingam, S., Subramaniam, D., Houchen, C., Ihnat, M., Anant, S., Ramanujam, R.P. Curcumin and turmeric attenuate arsenic-induced angiogenesis in ovo. Altern Ther Health Med. 2010 Mar-Apr;16(2):12-4. PubMed PMID: 20232614.

May, R., Sureban, S.M., Lightfoot, S.A., Hoskins, A.B., Brackett, D.J., Postier, R.G., Ramanujam, R., Rao, C.V., Wyche, J.H., Anant, S., Houchen, C.W. Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas. Am J Physiol Gastrointest Liver Physiol. 2010 Aug;299(2):G303-10. Epub  2010 Jun 3. PubMed PMID: 20522640.

Mondalek, FG., Ponnurangam, S., Govind, J., Houchen, C., Anant, S., Pantazis, P., Ramanujam, R.P. Inhibition of angiogenesis- and inflammation-inducing factors in human colon cancer cells in vitro and in ovo by free and nanoparticle-encapsulated redox dye, DCPIP. J Nanobiotechnology. 2010 Jul 15;8:17. PubMed PMID: 20633276; PubMed Central PMCID: PMC2911398.

Lagisetty. P., Vilekar, P., Sahoo, K., Anant, S., Awasthi ,V. CLEFMA-An anti-proliferative curcuminoid from structure-activity relationship studies on 3,5-bis(benzylidene)-4-piperidones. Bioorg Med Chem. 2010 Aug 15;18(16):6109-6120. Epub 2010 Jun 22. PubMed PMID: 20638855.

Anant, S. Houchen, C.W., Pawar, V. and Ramalingam, S. 2010. Role of RNA-Binding Proteins in Colorectal Carcinogenesis. Curr Colorectal Cancer Rep. 2010 Mar 2;6(2):68-73.

Subramaniam, D., Ramalingam, S., Houchen, C.W., Anant, S. Cancer stem cells: a novel paradigm for cancer prevention and treatment. Mini Rev Med Chem. 2010 May;10(5):359-71.

Last modified: Apr 15, 2014

Contact

Shrikant Anant, Ph.D.
Professor
Kansas Mason Professor for Cancer Research
Associate Director for Prevention and Cancer Control
Associate Dean for Research
The Tom and Teresa Walsh Professorship in Cancer Prevention and Survivorship

3901 Rainbow Blvd. Mail Stop 3043
4019 WHE
Kansas City, KS 66160

P: 913-945-6334
F: 913-946-6327
sanant@kumc.edu

ID=x6550