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Hofseth, Lorne
Lorne Hofseth , Ph.D.
Associate Professor
Office Location
USC Campus
CLS 513B

715 Sumter Street

Columbia
, SC29208
Phone: (803) 777-2080

hofseth@sccp.sc.edu
Links
PubMed Listings
Direct Link to Profile
 
  • Simon Fraser University, Canada, Doctor of Philosophy, 1996
  • Postdoc, Michigan State University, 1996-1999
  • Postdoc, National Cancer Institute, 1999-2003
Chronic inflammation is dangerous to human health.  It drives many prevalent diseases in our society, including heart disease, diabetes, Alzheimer's, and cancer.  Current treatment strategies to dampen signs and symptoms of chronic inflammation are limited, and fraught with side-effects.  Often this is because of the dual roles of one molecule in different parts of the body.  Our lab studies the interaction between chronic inflammation and cancer in cell culture, animal models, and in clinical trials.  We have been studying the ability of complementary and alternative medicines (CAMs) to reduce inflammation.  We have found that CAMs, such as Ginkgo Biloba, Resveratrol, and American Ginseng prevent and treat mouse colitis.  We are also carrying out clinical trials to examine the role of juice extracts to reduce systemic inflammation, and improve overall health. Finally, in collaboration with medicinal chemists, we have been able to identify novel synthetic inhibitors of colitis and the colitis-to-cancer sequence.  Our bench-to-bedside approach will have far-reaching health implications on millions of people suffering from auto-immune and chronic inflammatory diseases
  • Hussain SP, Hofseth LJ, Harris C.C.  Radical causes of cancer. Nature - Cancer Reviews, 3 (4): 276-285, 2003.
  • Hofseth, L. J., Saito, S., Hussain, S. P., Espey, M. G., Miranda, K. M., Araki, Y., Jhappan, C., Higashimoto, Y., He, P., Linke, S.P., Quezado, M.M., Zurer, I., Rotter, V., Wink, D. A., Appella, E. and Harris, C. C.  Nitric oxide-induced cellular stress and p53 activation in chronic inflammation.  Proceedings of the National Academy of Sciences, 100(1): 143-148, 2003.
  • Hofseth LJ, Khan MA, Ambrose M, Nikolayeva O, Xu-Welliver M, Kartalou M, Hussain SP, Roth RB, Zhou X, Mechanic LE, Zurer I, Rotter V, Samson LD, Harris CC.  The adaptive imbalance in base excision repair enzymes generates microsatellite instability in chronic inflammation.  Journal of Clinical Investigation, 112, 1887-94, 2003
  • Ying L, Marino J, Hussain SP, Khan MA, You S, Hofseth AB, Trivers GE, Dixon DA, Harris CC, Hofseth LJ. Chronic Inflammation Promotes Retinoblastoma Protein Hyperphosphorylation and E2F1 Activation. Cancer Research, 2005;65:9132-36.
  • Hofseth LJ and Ying L.  Identifying and Defusing Weapons of Mass Inflammation in Carcinogenesis.  BBA – Reviews on Cancer, 1765, 74-84, 2006.
  • Hofseth LJ and Wargovich MJ.  Inflammation, Cancer, and Targets of Ginseng.  J. Nutrition, 137: 183S-185S, 2007
  • Ying L and Hofseth LJ.  An emerging role for endothelial nitric oxide synthase in inflammation and cancer.  Cancer Research, 67:1407-10, 2007
  • Ying L, Hofseth AB, Browning DD, Nagarkatti M, Nagarkatti PS, and Hofseth LJ.  Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation.  Cancer Research, 67, 9286-9293, 2007.
  • Kotakadi V, Jin Y, Hofseth AB, Ying L, Cui X, Volate S, Chumanevich A, Wood P, Price R, McNeal A, Singh UP, Singh N, Nagarkatti M, Nagarkatti P, Matesic LE, Auclair K, Wargovich MJ, Hofseth LJ.  Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis.  Carcinogenesis, 29: 1799-806, 2008.   
  • Jin Y, Kotakadi VS, Ying L, Hofseth AB, Cui X, Wood PA, Windust A, Matesic LE, Pena EA,  Chiuzan C, Singh NP, Nagarkatti M, Nagarkatti PS, Wargovich MJ, Hofseth LJ. American  ginseng suppresses inflammation and DNA damage associated with mouse colitis.  Carcinogenesis, 29: 2351-59, 2008.
  • Jones LE, Ying L, Hofseth AB, Jelezcovab E, Sobol RW, Ambs S, Harris CC, Espey MG, Hofseth LJ,  Wyatt MD.  Reactive nitrogen species alter alkyladenine DNA glycosylase activity by post-translational protein modifications. Carcinogenesis., 30:2123-9, 2009.
  • Jin Y, Hofseth AB, Cui X, Windust AJ, Chumanevich AA, Matesic LE, Singh NP, Nagarkatti M, Nagarkatti PS, and Hofseth LJ.  American ginseng suppresses colitis through p53 mediated apoptosis of inflammatory cells.  Cancer Prevention Research, 3:339-7, 2010.
  • Cui X, Jin Y, Hofseth AB, Pena E, Habiger J, Chumanevich A, Poudyal D, Nagarkatti M, Nagarkatti P, Singh U, and Hofseth LJ.  Resveratrol suppresses colitis and colon cancer associated with colitis.  Cancer Prevention Research, 3, 549-559, 2010.
  • Jin Y, Cui X, Singh UP, Chumanevich AA, Harmon B, Cavicchia P, Hofseth AB, Kotakadi V, Stroud B, Volate SR, Hurley TG, Hebert JR and Hofseth LJ.  Systemic inflammatory load in humans is suppressed by consumption of two formulations of dried, encapsulated juice concentrate.  Molecular Nutrition and Food Research, 54(10):1506-14, 2010.
  • Hofseth LJ, Singh UP, Singh NP, Nagarkatti M, Nagarkatti PS.  Taming the beast within: resveratrol suppresses colitis and prevents colon cancer. Aging, 2, 183-4, 2010.
  • Chumanevich AA, Poudyal D, Cui X, Davis T, Wood PA, Smith CD, and Hofseth LJ. Suppression of colitis-driven colon cancer in mice by a novel small molecule inhibitor of sphingosine kinase.  Carcinogenesis, 31(10):1787-93, 2010.
  • Cui X, Jin Y, Poudyal D, Chumanevich AA, Davis T, Windust A, Hofseth AB, Wu W, Habiger J, Pena EA, Wood PA, Nagarkatti M, Nagarkatti P, Hofseth LJ.  Mechanistic insight into the ability of American ginseng to suppress colon cancer associated with colitis.  Carcinogenesis, 31(10):1734-41, 2010.
  • Chumanevich AA, Causey CP, Knuckley BA, Jones JE, Poudyal D, Chumanevich AP, Davis T, Matesic LE, Thompson PR, Hofseth LJ.  Suppression of colitis in mice by Cl-amidine: a novel peptidylarginine deiminase inhibitor.  Am J Physiol Gastrointest Liver Physiol.  300(6):G929-38, 2011.
  • Causey CP, Jones JE, Slack JL, Kamei D, Jones LE, Subramanian V, Knuckley B, Ebrahimi P, Chumanevich AA, Luo Y, Hashimoto H, Sato M, Hofseth LJ, Thompson PR.  The development of N-a-(2-carboxyl)benzoyl-N5-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-a-(2-carboxyl)benzoyl-N5-(2-Chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) as second generation Protein Arginine Deiminase (PAD) inhibitors.  J Med Chem. 54, 6919-35, 2011. 
  • Hofseth LJ, Matesic LE.  Editorial: an apple a day keeps colitis away.  J. Leukoc Biol., 90, 1037-1038, 2011.
  • Poudyal D, Le PM, Davis T, Hofseth AB, Chumanevich AP, Chumanevich, AA, Wargovich MJ, Nagarkatti M, Nagarkatti, PS, Windust AJ, and Hofseth LJ. A hexane fraction of american ginseng suppresses mouse colitis and associated colon cancer: anti-inflammatory and pro-apoptotic mechanisms. Cancer Prevention Research , 5(4):685-96, 2012.
  • Cui X, Jin Y, Singh UP, Chumanevich AA, Harmon B, Cavicchia P, Hofseth AB, Kotakadi V, Poudyal D, Stroud B, Volate SR, Hurley TG, Hebert JR, Hofseth LJ.  Suppression of DNA damage in human peripheral blood lymphocytes by a juice concentrate: a randomized, double-blind, placebo-controlled trial. Mol Nutr Food Res. 56:666-70, 2012.
  • Shaked H, Hofseth LJ, Chumanevich A, Chumanevich AA, Wang J, Wang Y, Taniguchi K, Guma M, Shenouda S, Clevers H, Harris CC, Karin M. Chronic epithelial NF-?B activation accelerates APC loss and intestinal tumor initiation through iNOS up-regulation. Proc Natl Acad Sci U S A. 109:14007-12, 2012.
  • Poudyal D, Cui X, Mai Le P, Davis T, Hofseth AB, Jin Y, Chumanevich AA, Wargovich MJ, Nagarkatti M, Nagarkatti PS, Windust A, Hofseth LJ.  A limited role of p53 on the ability of a Hexane fraction of American ginseng to suppress mouse colitis. J Biomed Biotechnol. 12:785-9, 2012.
  • Bicker KL, Subramanian V, Chumanevich AA, Hofseth LJ, Thompson PR. Seeing citrulline: development of a phenylglyoxal-based probe to visualize protein citrullination. J Am Chem Soc.134:17015-8, 2012.
  • Bicker KL, Anguish L, Chumanevich AA, Cameron MD, Cui X, Witalison E, Subramanian V, Zhang X, Chumanevich AP, Hofseth LJ, Coonrod SA, Thompson PR.  D-Amino Acid-Based Protein Arginine Deiminase Inhibitors: Synthesis, Pharmacokinetics, and in Cellulo Efficacy.  ACS Med. Chem. Lett., 3(12), 1081-1085, 2012.
  • Cui X, Witalison EE, Chumanevich AP, Chumanevich AA, Poudyal D, Subramanian V, Schetter  AJ, Harris CC, Thompson PR, Hofseth LJ. The Induction of microRNA-16 in Colon Cancer  Cells by Protein Arginine Deiminase Inhibition Causes a p53-Dependent Cell Cycle Arrest.   PLoS One. 8(1):e53791, 2013.

Grants and Funding

Current:
  • 1. 1R01CA151304-01A1
    Agency:  NIH/NCI
    Title: Targeting Protein Arginine Deiminases to Prevent Colitis and Colon Cancer
    Amount:  $1,321,090 Direct   Duration:  7/1/2011- 6/31/2016
    Role:  Principle Investigator
  • 2. 1R03CA171326-01A1
    Agency:  NIH/NCI
    Title: Colon cancer chemoprevention by the anti-inflammatory drug, Quinacrine 
    Amount:  $100,000 Direct   Duration:  3/1/2013- 2/28/2015
    Role:  Principle Investigator

Previous:

  • 3. 1P01AT003961-01A1
    Agency:  NIH/NCCAM
    Title: Center for Complementary and Alternative Medicine on Chronic Inflammatory and  Autoimmune Diseases
    Project Title:  Anti-inflammatory mechanisms of american ginseng in colitis    Amount:  $875,000 Direct   Duration:  12/01/07-11/30/2012 
    Role:  Project PI
  • 4.  1R03CA141758-01
    Agency:  NIH/NCI
    Title:  Colon Cancer Chemoprevention by Dietary Resveratrol   
    Amount:  $100,000 Direct   Duration:  7/01/09-6/30/2011
    Role:  Principle Investigator
  • 5. R03CA137736-01
    Agency:  NIH/NCI
    Title:  Sphingosine Kinase as a Target for Cancer Chemoprevention  
    Amount:  $100,000 Direct   Duration:  9/1/2008-8/31/2010 
    Role:  Principle Investigator
  • 6. R21 DK071541-01A1
    Agency:  NIH/NIDDK
    Title:  Nitric oxide as a target for dietary intervention in colitis   
    Amount:  $210,000 Direct   Duration:  4/1/06-3/31/2008 
    Role: Co-Investigator (100% of experiments in my lab)
  • 7. Seed Grant
    Agency:  USC Center for Colon Cancer Research
    Title:  Intervention of autoimmune diseases by a novel anti-inflammatory molecule 
    Amount:  $50,000 Direct   Duration:  9/1/2008-8/31/2009 
    Role:  Principle Investigator
  • 8. Contract
    Agency:  NSA
    Title:  A prospective study to examine the effects of JuicePlus on global body inflammatory load in healthy people:  A double-blind, placebo controlled trial    Amount:  $194,360 Direct   Duration:  1/1/2007-7/1/2010 
    Role:  Principle Investigator
  • 9. Seed Grant 109 R06-05
    Agency:  South Carolina Cancer Center
    Title:  The retinoblastoma pathway in inflammation and cancer   
    Amount:  $25,000 Direct   Duration:  4/1/2006-3/31/2008 
    Role:  Principle Investigator
  • 10. Seed Grant GC-3319-05-44598CM
    Agency:  Hollings Cancer Center
    Title:  Nitric oxide alters the structure and function of the human BER enzyme, MPG. 
    Amount:  $30,000 Direct   Duration:  2/1/2006-1/31/2007
    Role:  Principle Investigator
  • 11. P20RR17698-01 (COBRE Center for Colon Cancer Research)
     Agency:  NIH/NCRR
     Title:  Center for Colon Cancer Research
     Amount:  $371,381 Direct   Duration:  01/01/04-06/31/2008
     Role:  Target Faculty