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Raghu Sinha
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Title Associate Professor
Institution College of Medicine
Department Biochemistry and Molecular Biology
Division Biochemistry/Molecular Biology
Address 500 University Drive Hershey PA 17033
 Mailbox: CH76
Telephone 7175314663
Email
Background
PREFERRED TITLE/ROLE:

Associate Professor of Biochemistry and Molecular Biology

SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):

Penn State Hershey Cancer Institute, Chemical Carcinogenesis and Chemoprevention

GRADUATE PROGRAM AFFILIATIONS:

Biochemistry and Molecular Biology

EDUCATION:

M.S., Biophysics, Panjab University, Chandigarh, India, 1985
Ph.D., Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India, 1991
Postdoctoral Training, Baylor College of Medicine, 1991-1995

NARRATIVE:

Cancer Prevention

I believe prevention is a practical, non-invasive and dependable approach to control breast and other organ cancers. Knowledge of the mechanisms by which a promising chemopreventive agent interrupts cancer cell proliferation is very critical to design effective cancer prevention strategies. New model systems are essential bearing in mind the heterogeneity of the disease especially in breast cancer. For that reason, several outgrowths of premalignant stage of breast cancer would be best suited to examine the block of molecular and / or cellular events by chemopreventive agents, leading to an effective prevention strategy. My laboratory focuses on establishing model systems to investigate molecular mechanisms of prevention in breast and prostate cancers.


Model Systems for Breast Cancer Prevention

We have developed an in vitro model for mouse mammary epithelial tumor cells that allows cells to be synchronized by growth factor withdrawal. These cells are being examined for various components of Ras-Raf-Erk pathway (proliferation), PI3-Kinase-PDK-AKT pathway (survival) and for the role of caspases (apoptosis). We have established the effect of organoselenium compounds (such as Se-methylselenocysteine and methylseleninic acid) on several cell cycle regulatory molecules such as RB, PCNA, PKC, p21, p27, cyclin D1, cyclin E, cyclin A, cdk2, cdk4 and cdc2 protein phosphorylations, protein-protein interactions and kinase reactions in this model. More recently, my laboratory has identified osteopontin as one of the potential targets of selenium in mouse mammary tumorigenesis. We are currently extending these findings to human breast cells. Using cDNA microarray technology and 2D-gel electrophoresis coupled with phosphorylations of various proteins of these tools, I am asking important questions: (1) what genes are turned on or off in various stages of breast cancer? And which of these genes respond to selenium treatment? (2) How can this information be combined with genomics of normal mammary gland development? (3) What are the main protein-protein interactions during mammary carcinogenesis? And how do these interactions respond to selenium treatment during the stages of immortality, transformation and neoplasia.

In our laboratory we have the expertise to grow primary cells from mouse mammary gland and human breast tissue in collagen gel that provides a 3-dimensional environment to form tubular structures. In this model system, several biological markers including ER, PR, Ki67, SMA and Her-2/neu can be studied along with signal transduction pathways and apoptosis. Furthermore, we are using a unique approach of generating a xenograft model for premalignant breast disease; growing premalignant human breast cells in collagen gel prior to transplantation in nude mice mammary fat pads. These models offer the ability to investigate the interactions of the cellular and molecular components of the organ system with promising anti-cancer agents and / or potential growth inhibitors.


Strategies for Prostate Cancer Prevention

We are investigating relevant target molecules that can be modulated to impede growth of prostate cancer using chemopreventive agents. Our hypothesis is that selenium compounds in particular may act by modulating redox-sensitive signal transduction proteins thereby regulating proliferation and / or apoptosis of these cells. Using the 2D-gel electrophoresis technique we have identified several differentially expressed spots by mass spectroscopy. These proteins include cofilin-2, HnRNP and peroxiredoxins. In addition, we are investigating the active components of selenized-yeast that may be responsible for prevention of human prostate cancer. Our goal is to determine the molecular mechanisms by which selenium inhibits prostate cancer in the TRAMP model.
Publications
1. Sheikh H, Abdulghani J, Ali S, Sinha R, Lipton A. Impact of genetic targets on prostate cancer therapy. Adv Exp Med Biol. 2013; 779:359-83.
  View in: PubMed
 
2. Belda BJ, Thompson JT, Sinha R, Prabhu KS, Vanden Heuvel JP. The dietary fatty acid 10E12Z-CLA induces epiregulin expression through COX-2 dependent PGF(2a) synthesis in adipocytes. Prostaglandins Other Lipid Mediat. 2012 Oct; 99(1-2):30-7.
  View in: PubMed
 
3. Facompre ND, Sinha I, El-Bayoumy K, Pinto JT, Sinha R. Remarkable inhibition of mTOR signaling by the combination of rapamycin and 1,4-phenylenebis(methylene)selenocyanate in human prostate cancer cells. Int J Cancer. 2012 Nov 1; 131(9):2134-42.
  View in: PubMed
 
4. Sinha I, Null K, Wolter W, Suckow MA, King T, Pinto JT, Sinha R. Methylseleninic acid downregulates hypoxia-inducible factor-1a in invasive prostate cancer. Int J Cancer. 2012 Mar 15; 130(6):1430-9.
  View in: PubMed
 
5. Sinha R, Sinha I, Facompre N, Russell S, Somiari RI, Richie JP, El-Bayoumy K. Selenium-responsive proteins in the sera of selenium-enriched yeast-supplemented healthy African American and Caucasian men. Cancer Epidemiol Biomarkers Prev. 2010 Sep; 19(9):2332-40.
  View in: PubMed
 
6. Facompre ND, El-Bayoumy K, Sun YW, Pinto JT, Sinha R. 1,4-phenylenebis(methylene)selenocyanate, but not selenomethionine, inhibits androgen receptor and Akt signaling in human prostate cancer cells. Cancer Prev Res (Phila). 2010 Aug; 3(8):975-84.
  View in: PubMed
 
7. Desai D, Sinha I, Null K, Wolter W, Suckow MA, King T, Amin S, Sinha R. Synthesis and antitumor properties of selenocoxib-1 against rat prostate adenocarcinoma cells. Int J Cancer. 2010 Jul 1; 127(1):230-8.
  View in: PubMed
 
8. Pinto JT, Lee JI, Sinha R, MacEwan ME, Cooper AJ. Chemopreventive mechanisms of a-keto acid metabolites of naturally occurring organoselenium compounds. Amino Acids. 2011 Jun; 41(1):29-41.
  View in: PubMed
 
9. Lee JI, Nian H, Cooper AJ, Sinha R, Dai J, Bisson WH, Dashwood RH, Pinto JT. Alpha-keto acid metabolites of naturally occurring organoselenium compounds as inhibitors of histone deacetylase in human prostate cancer cells. Cancer Prev Res (Phila). 2009 Jul; 2(7):683-93.
  View in: PubMed
 
10. Singh U, Null K, Sinha R. In vitro growth inhibition of mouse mammary epithelial tumor cells by methylseleninic acid: involvement of protein kinases. Mol Nutr Food Res. 2008 Nov; 52(11):1281-8.
  View in: PubMed
 
11. Sinha R, Pinto JT, Facompre N, Kilheffer J, Baatz JE, El-Bayoumy K. Effects of naturally occurring and synthetic organoselenium compounds on protein profiling in androgen responsive and androgen independent human prostate cancer cells. Nutr Cancer. 2008; 60(2):267-75.
  View in: PubMed
 
12. Pinto JT, Sinha R, Papp K, Facompre ND, Desai D, El-Bayoumy K. Differential effects of naturally occurring and synthetic organoselenium compounds on biomarkers in androgen responsive and androgen independent human prostate carcinoma cells. Int J Cancer. 2007 Apr 1; 120(7):1410-7.
  View in: PubMed
 
13. El-Bayoumy K, Sinha R, Pinto JT, Rivlin RS. Cancer chemoprevention by garlic and garlic-containing sulfur and selenium compounds. J Nutr. 2006 Mar; 136(3 Suppl):864S-869S.
  View in: PubMed
 
14. El-Bayoumy K, Das A, Narayanan B, Narayanan N, Fiala ES, Desai D, Rao CV, Amin S, Sinha R. Molecular targets of the chemopreventive agent 1,4-phenylenebis (methylene)-selenocyanate in human non-small cell lung cancer. Carcinogenesis. 2006 Jul; 27(7):1369-76.
  View in: PubMed
 
15. El-Bayoumy K, Sinha R. Molecular chemoprevention by selenium: a genomic approach. Mutat Res. 2005 Dec 11; 591(1-2):224-36.
  View in: PubMed
 
16. El-Bayoumy K, Sinha R. Mechanisms of mammary cancer chemoprevention by organoselenium compounds. Mutat Res. 2004 Jul 13; 551(1-2):181-97.
  View in: PubMed
 
17. El-Bayoumy K, Das A, Boyiri T, Desai D, Sinha R, Pittman B, Amin S. Comparative action of 1,4-phenylenebis(methylene)selenocyanate and its metabolites against 7,12-dimethylbenz[a]anthracene-DNA adduct formation in the rat and cell proliferation in rat mammary tumor cells. Chem Biol Interact. 2003 Oct 25; 146(2):179-90.
  View in: PubMed
 
 
Keyword
Last Name
Institution
    
 
 
 
Keywords   
Organoselenium Compounds
Prostatic Neoplasms
Selenium
Antineoplastic Agents
Receptors, Androgen
See all (111) keywords
Co-Authors  
Amin, Shantu
Desai, Dhimant
El bayoumy, Karam
King, Tonya
Sinha, Indu
See all (10) people
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