Research/Scholarly Activities

Division Statement | Faculty | Research/Scholarly Activities | Fellowship | Quillen ETSU Physicians

Scholarship in the Division of Hematology/Oncology

Scholarship opportunity is available to all interested medical students, internal medicine residents and medical oncology fellows.  Active areas of scholarship opportunity include patient-physician communication, best practices and high value medicine, palliative and end of life topics, topical reviews and laboratory research in cancer chemoprevention.  Opportunities for research through collaborations with the College of Pharmacy, Pediatric Research and Biomedical Sciences can also be worked out.  Mentorship of scholarship activities will be made available for those interested.  

Cancer Prevention Research

Krishnan lab is currently focused on understanding the mechanisms that allow tocopherols and tocotrienols to selectively target cancer cells for cell death and apoptosis. Tocopherols are chemopreventive agents based on 1) several epidemiological studies showing an inverse relationship between serum vitamin E levels and incidence of neoplasia at various sites and 2) numerous experimental and pre-clinical cancer studies that show the chemopreventive potential of tocopherols and tocotrienols. Recent data indicate that gamma-tocopherol is more effective than alpha-tocopherol in suppressing neoplastic transformation. Further data is indicating that the tocotrienols are more potent than the tocopherols. The mechanistic basis of these cancer preventive functions is being explored. Projects will explore new targets of vitamin E action, effects of tocotrienol in combination with other nutrients and cancer prevention drugs, potencies of new synthetic forms of vitamin E, and effects of vitamin E forms on preinvasive lesions in rodent models of prostate, pancreatic and colon cancer.

Collaborators
Kanishka Chakraborty MD, Assistant Professor of Medicine, Department of Internal Medicine

William Stone PhD. Professor of Pediatric Research, Department of Pediatrics, East Tennessee State University, Johnson City, TN
Victoria Palau PhD, Associate Professor, Bill Gatton College of Pharmacy, Johnson City, TN
Sharon Campbell PhD, Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN

Key publications

Original Articles

1.Campbell S, Stone W, Lee S, Whaley S, Yang H, Qui M, Goforth P, Sherman D, McHaffie D, Krishnan K. Comparative Effects of RRR Alpha- and RRR Gamma-Tocopherol on Proliferation and Apoptosis in Human Colon Cancer Cell Lines. BMC Cancer 2006. 6: 13. PMID: 16417629

2.Ahn K, Sethi G, Krishnan K, Aggarwal B. -Tocotrienol Inhibits Nuclear Factor-kappaB Signaling Pathway Through Inhibition of RIP and TAK1 Leading to Suppression of Antiapoptotic Gene Products and Potentiation of Apoptosis. J Biol Chem. 2007 Jan 5. 282(1): 809-820. Epub 2006 Nov 17. PMID: 17114179

3.Campbell SE, Musich PR, Whaley SG, Stimmel JB, Leesnitzer LM, Dessus-Babus S, Duffourc M, Stone W, Newman RA, Yang P, Krishnan K. Gamma Tocopherol Upregulates the Expression of 15-S-HETE and Induces Growth Arrest Through a PPAR Gamma-Dependent Mechanism in PC-3 Human Prostate Cancer Cells.. Nutrition and Cancer, 2009 Sept. 61: 649-662. PMID: 19838939

4.Campbell SE, Rudder B, Phillips RB, Whaley SG, Stimmel JB, Leesnitzer LM, Lightener J, Dessus-Babus S, Duffourc M, Stone WL, Menter DG, Newman RA, Yang P, Aggarwal BB, Krishnan K. γ-Tocotrienol induces growth arrest through a novel pathway with TGF2 in prostate cancer. Free Radical Biology and Medicine, 2011 May 15. 50(10): 1344-54. PMID: 21335085

5.Shin-Kang S, Ramsauer VP, Lightner J, Chakraborty K, Stone W, Campbell S, Reddy S, Krishnan K. Tocotrienols inhibit Akt and Erk activation and suppress pancreatic cancer cell proliferation by suppressing the ErbB2 pathway. Free Radic Biol Med, 2011 Sep 15. 51(6): 1164-74. PMID: 21723941

6.Menter DG, Ramsauer VP, Harirforoosh S, Chakraborty K, Yang P, Hsi L, Newman RA, Krishnan K. Differential Effects of Pravastatin and Simvastatin on the Growth of Tumor Cells from Different Organ Sites. PLoS ONE 6(12): e28813. doi:10.1371/journal.pone.0028813. PMID: 22216116

7.Jiang YL, McGoldrick C, Yin D, Zhao J, Patel V, Brannon M, Lightner J, Krishnan K, Stone WL. A Specific Molecular Beacon Probe for the Detection of Human Prostate Cancer Cells. Biorganic Medicinal Chemistry Letters, Bioorg Med Chem Lett. 2012 Jun 1. 22(11): 3632-8. Epub 2012 Apr 19. Jun 1;22(11):3632-8. PMID: 22572577

8.Thomas CM, Wood III RC, Wyatt JE, Pendleton MH, Rodriguez OE, Torrenegra RD, Harirforoosh S, Ballester M, Lightner J, Krishnan K, Ramsauer VP. Anti-neoplastic activity of two flavone isomers derived from Gnaphalium elegans and Achyrocline bogotensis PLoS One, 2012. PMID: 22768128

9.Christopher A. McGoldrick, Yu-Lin Jiang, Victor Paromov, Marianne Brannon, Koyamangalath Krishnan, William L. Stone. Identification of Oxidized Protein Hydrolase as a Potential Prodrug Target in Prostate Cancer. BMC Cancer (in review), 2014

10.Rogers M, Kalra S, Moukharskaya J, Lightner J, Niyazi, M, Krishnan, K, Ramsauer V. Synergistic inhibition of prostate cancer cell (PC3) growth in vitro with low dose combinations of Simvastatin and Alendronate. BMC Cancer, 2014, in review.

Chapters

1.Krishnan K, Campbell SC, Stone WL. Overview of tocopherols in cancer chemoprevention. The Encyclopedia of Vitamin E. CABI Publishing, Oxford, UK, 2006.
2.Stone WL, Ramsauer VP, Campbell SE, Krishnan K. A targeted prostate cancer chemoprevention trial with tocotrienols. Tocotrienols: Vitamin E Beyond Tocopherols [Hardcover], second edition, 2011.
3.Krishnan K, Campbell SE, Stone WL. The role of vitamin E in prostate cancer. Oxidative Stress in Cancer Biology and Therapy, Oxidative Stress in Applied Basic Research and Clinical Practice. Springer Science + Business Media, LLC, 2012. 16.
4.Chakraborty K, Ramsauer VP, Stone WL, Krishnan K. Tocotrienols in the treatment and prevention of pancreatic cancer. Oxidative Stress and Dietary Antioxidants, Editors, Victor Preedy; Elsevier , Academic Press, 2013.

Cancer Education Modules Development
Dr. Krishnan is a Co-Principal Investigator in the five year NIH grant (1R25 CA111698-01A2). Through this grant, Dr. Krishnan is closely involved in collaboration with the Dept. of Family Medicine and Dept. of Storytelling. This is an R-25 NIH grant to build teaching modules to improve patient-physician communication on key aspects in oncology such as; breaking bad news, transition from curative to palliative care, living through cancer, end of life issues and spirituality in cancer care. His collaborators on this multidisciplinary grant includes: Forrest Lang MD, Fred Tudiver MD, Michael Floyd and Tom Bishop (Family Medicine), Joseph Sobol PhD (Story telling).

Current grant support

NIH R-25: Co-PI, PI: Forrest Lang MD. 1R25 CA111698-01A2
National Cancer Institute Special Emphasis Panel; Project Title: Instructional Modules to Improve Cancer Communication. Total costs: $ 1,575,015 July 2009-June 2014

American Society of Hematology, Hematology Opportunities for the Next Generation of Research Scientists (HONORS Award) to Ko Maung, mentor: K. Krishnan, amount $5000 plus travel award; Project title: Tocotrienols and Statins in leukemia; 2013-14