Professor and Research Cluster Coordinator
Department: Pharmacology, Physiology and Toxicology
Cluster Affiliations: Toxicology and Environmental Health Sciences; Cancer Biology, and Cardiovascular Disease, Obesity, and Diabetes
Office: BBSC 435-G | Laboratory: BBSC 406
Phone: (304) 696-7332
Projects in my lab:
Project #1 The effect of herbal agents on susceptibility to drug toxicity: Billions of dollars are spent in the United States each year by individuals on nutritional and herbal supplements. We are investigating the mechanism for reduction of hepatic acetaminophen toxicity by S-adenosyl-l-methionine (SAMe). This project is important since acetaminophen is the number one cause of drug induced liver failure in the U.S. This project is evaluating the cellular effects of SAMe that are responsible for attenuating acetaminophen toxicity. We are also comparing SAMe to the currently used clinical treatment for acetaminophen to evaluate SAMe’s effectiveness.
Project #2 Evaluating methods to reduce the side effects of cancer chemotherapeutic drugs: Adverse effects of cancer chemotherapy agents limit the duration of treatment in many patients. This project is evaluating the protective effect of natural products on cisplatin nephrotoxicity. Cisplatin is a widely used cancer chemotherapeutic agent. Unfortunately, the two principal side effects of cisplatin treatment are renal and peripheral nerve dysfunction. We have found an agent that can reduce the renal toxicity in isolated renal tissue. We are evaluating whether resveratrol impacts cell signaling or alters oxidative stress as part of its protective effect against cisplatin.
Project #3 Exploration of new agents to reduce cancer cell growth: This is a collaborative project with Dr. Piyali Dasgupta. We are exploring whether natural products can slow lung cancer growth. In order to profile the activity of these compounds, we are characterizing the plasma, tissue and tumor levels of these compounds. Further, we are examining how long these substances remain in the body and their pharmacokinetic profile.
Project #4 Susceptibility to oxidative stress in diabetes: Over 29 million Americans are diagnosed with diabetes mellitus. Diabetes is associated with a higher risk of kidney disease and renal failure. The predisposition to renal dysfunction may involve a defect in the ability to protect the kidney from damage by free radicals. In this project we are evaluating: a) the predisposition to renal damage by renal toxicants that are known to induce free radical damage; b) investigate the cellular and subcellular abnormalities induced by diabetes; c) initiate studies of possible interventions to slow the progression of renal dysfunction.
For a complete list of publications, access PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25246065 S-adenosyl-l-methionine protection of acetaminophen mediated oxidative stress and identification of hepatic 4-hydroxynonenal protein adducts by mass spectrometry. Brown JM, Kuhlman C, Terneus MV, Labenski MT, Lamyaithong AB, Ball JG, Lau SS, Valentovic MA. Toxicol. Appl. Pharmacol. 2014 Dec 1;281(2):174-84. PMID: 25246065
http://www.ncbi.nlm.nih.gov/pubmed/26808022 The role of biotransformation and oxidative stress in 3,5-dichloroaniline (3,5-DCA) induced nephrotoxicity in isolated renal cortical cells from male Fischer 344 rats. Racine CR, Ferguson T, Preston D, Ward D, Ball J, Anestis D, Valentovic M, Rankin GO. Toxicology. 2016 Feb 3;341-343:47-55 PMID 26808022
http://www.ncbi.nlm.nih.gov/pubmed/24239945 Resveratrol attenuates cisplatin renal cortical cytotoxicity by modifying oxidative stress. Valentovic MA, Ball JG, Brown JM, Terneus MV, McQuade E, Van Meter S, Hedrick HM, Roy AA, Williams T.Toxicol In Vitro. 2014 Mar;28(2):248-57. PMID:24239945
http://www.ncbi.nlm.nih.gov/pubmed/25307998 Bioavailability of capsaicin and its implications for drug delivery.Rollyson WD, Stover CA, Brown KC, Perry HE, Stevenson CD, McNees CA, Ball JG, Valentovic MA, Dasgupta P. J Control Release. 2014 Dec 28;196:96-105. PMID: 25307998
http://www.ncbi.nlm.nih.gov/pubmed/24878626 Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway.Lau JK, Brown KC, Dom AM, Witte TR, Thornhill BA, Crabtree CM, Perry HE, Brown JM, Ball JG, Creel RG, Damron CL, Rollyson WD, Stevenson CD, Hardman WE, Valentovic MA, Carpenter AB, Dasgupta P. Apoptosis. 2014 Aug;19(8):1190-201. PMID:24878626
http://www.ncbi.nlm.nih.gov/pubmed/24634789 Transsulfuration Is a Significant Source of Sulfur for Glutathione Production in Human Mammary Epithelial Cells. Belalcázar AD, Ball JG, Frost LM, Valentovic MA, Wilkinson J 4th. ISRN Biochem. 2014;2013:637897. PMID: 24634789
http://www.ncbi.nlm.nih.gov/pubmed/18840895 Characterization of a novel model for investigation of radiocontrast nephrotoxicity. Harmon RC, Duffy SP, Terneus MV, Ball JG, Valentovic MA. Nephrol Dial Transplant. 2009 Mar;24(3):763-8. PMID: 18840895
Graduates from Valentovic Lab
J. Michael Brown, PhD, PharmD (2012) – Pharmacy Fellow
Marcus Terneus, PhD (2006) – Senior Manager, Global Environmental, Health and Safety Occupational Toxicology, Mylan [Pharmaceuticals]
R. Chris Harmon, MD, PhD (2003) – Gastroenterologist, Augusta Health
Sama Kalou, MS, MD (2003)
Nizar Noureddine, MS, PhD (2002) – Cardiologist
Jennifer Minigh, PhD (May 2002) Senior Manager Global Regulatory Writing, Amgen
Laurie Scott, PhD (1989) Toxicologist Proctor and Gamble International