Valentovic

Sundaram
Monica Valentovic, PhD
Professor & Research Cluster Coordinator

Phone: (304) 696-7332
valentov@marshall.edu

Research Statement

My educational background has provided an emphasis on pharmacology, pharmacokinetics, drug metabolism and toxicology. I have published over 95 research papers, over 150 abstracts and 7 book chapters on drug pharmacokinetics, toxicity and metabolism of xenobiotics. My graduate education provided a strong background in the area of drug metabolism as well as toxicology. I have considerable experience with HPLC analysis of drugs, biomarkers of oxidative stress, endogenous substances (prostaglandins, ADP and ATP) as well as cellular markers of toxicity. We have considerable experience examining alterations in proteins due to toxicity. My laboratory has 2 Alliance Waters HPLC systems that are dedicated to analysis of pharmaceutical agents, endogenous substances and toxins. Our laboratory is active in examination of the mechanisms of toxicity of drugs and environmental agents in vivo as well as in vitro. I have been on numerous NIH study sections and have served as Chair of more than 6 NIH study sections. I was the 2013 recipient of the Marshall University Distinguished Artist and Scholars Award in Science and Technology award which is given to a faculty member as an achievement of research activity. My professional roles include being the Chair Elect of the Division of Toxicology for the American Society of Pharmacology and Experimental Therapeutics and will become Chair in June 2017 of the Division of Toxicology.

Our laboratory is exploring new interventions that will reduce the adverse effects of drugs. We have recently focused on examining ways to reduce the toxicities of cancer chemotherapy agents. Projects available in my lab:

Projects #1 Reducing serious cancer chemotherapy side effects. This is an ongoing project that has been funded by a federal grant from NIH. Our laboratory is evaluating new compounds that may reduce the adverse effects experienced by individuals treated with cancer chemotherapy drugs. In addition, another goal of this project is to come up with methods to improve the effectiveness of the cancer chemotherapeutic agents while lessening the side effects. This project has clear clinical relevance and is translational. One of the projects in this area is a collaborative effort with Dr. Piyali Dasgupta and is funded by NIH. We are investigating cellular changes in toxicity, specifically we want to explore changes in the mitochondria as well as post-translational modifications of proteins caused by exposure to two cancer chemotherapy drugs, doxorubicin or cisplatin. The studies examining doxorubicin are currently funded by an NIH Subaward Pilot grant.

Projects #2 Identification of ways to reduce the liver damage of acetaminophen overdose. Acetaminophen (APAP) is a common ingredient in nonprescription pain, fever and flu remedies. APAP can cause liver damage when used in excess and is the #1 cause of drug induced liver failure.  The purpose is to investigate new ways to lower the severe liver failure associated with acetaminophen overdose. Acetaminophen is an over the counter agent for pain and fever that is very safe but when taken in excess can damage the liver and kidney. Once this damage occurs a liver transplant may be the only alternative.  This project is examining how a nutraceutical, S-adenosylmethionine (SAMe) reduces acetaminophen mediated liver damage.

Project #3 Mechanisms to reduce diabetic renal complications. Diabetes mellitus afflicts 1 in 50 Americans. Diabetes is the major cause of kidney failure and why people must go on dialysis in the United States. The long-term goal is to examine what makes the diabetic more susceptible to kidney failure. These results may then be applied to develop new treatments for diabetics. Individuals (students or faculty) involved with this project will participate in examining cellular changes that may increase cellular stress in the diabetic kidney.

Project #4 Examination of the mechanism of renal damage by drugs including an antiviral drug and radiocontrast agents. Patients with HIV or hepatitis B must take antiviral agents to slow the progression of heir disease for very long periods of time. Side effects often occur after someone takes an antiviral agent for over 1 year. We are examining the mechanism of damage to the kidney by a commonly used antiviral agent. We are using a normal human proximal tubular epithelial cell culture model for this study. Another project is examining the renal damage of radiocontrast agents which are one of the leading causes of drug induced renal impairment in hospitalized patients. We are examining potential natural substances that may reduce renal damage to the proximal tubule following exposure to radiocontrast agents.

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

Current

Katie Brown, M.S. Research Technician
Morghan Getty Master’s Graduate Student

Rachel Murphy, Ph.D. Candidate
NASA Graduate WV Space Consortium Research Fellowship 06/01/2015-05/31/2017
Mechanisms of Oxidative Stress Associated with Tenofovir Nephrotoxicity

Dakota Ward, Ph.D. Candidate
NASA Graduate WV Space Consortium Research Fellowship for Dakota Ward 06/01/2016-05/31/2017
Mechanism of Radiocontrast Nephrotoxicity

Mason Dial Undergraduate
NASA Undergraduate Space Consortium Research Fellowship for Mason Dial 11/01/2016-05/01/2017
Cellular Mechanisms of Kaempferol Protection of Cisplatin Renal Cytotoxicity

Graduates

J. Michael Brown, PhD, PharmD (2012) – Hospital Pharmacist Huntington, WV VA Hospital
Marcus Terneus, PhD (2006), DABT – Senior Toxicologist, Drug Safety and Disposition –Animal Health, Boehringer Ingelheim
R. Chris Harmon, MD, PhD (2003) – Gastroenterologist, Colorado Springs, CO
Sama Kalou, MS, MD (2003)- Internal Medicine
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