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Howard Perry Glauert, Ph.D.
Professor, Graduate Center for Nutritional Sciences

222 Funkhouser Building
Lexington, KY 40506-0054
Telephone: (859) 257-7789
Fax: (859) 323-0061
e-Mail: hglauert@uky.edu

Academic Appointments:

• Graduate Center for Nutritional Sciences
• Graduate Center for Toxicology
• Member, Markey Cancer Center

Education:

• B.A., Biological Sciences, University of Missouri
• Ph.D., Nutrition, Michigan State University
• Postdoctoral Fellow, Environmental Toxicology Center and McArdle Laboratory
  for Cancer Research, University of Wisconsin

Awards:

• NIEHS Postdoctoral Fellow, University of Wisconsin
• Alexander von Humboldt Research Fellow, German Cancer Research Center,    Heidelberg, Germany
• NIH Research Career Development Award
• Outstanding Alumnus, Department of Food Science and Human Nutrition,    Michigan State University

Specific Interest in Nutrition:

Mechanisms of carcinogenesis induced by environmental chemicals and prevention by nutritional interventions

Research:

My main research interest has been to examine the mechanisms by which environmental chemicals induce liver cancer and the effect of nutrition, especially dietary antioxidants. Several diverse chemicals, including phenobarbital, peroxisome proliferators, and PCBs, have tumor promoting activity in the liver. The mechanisms by which these agents act is unclear, but may be related to the induction of oxidative stress. The production of active oxygen could lead to several deleterious changes in the cell, including lipid peroxidation, oxidative DNA damage, or changes in gene expression. The transcription factor NF-kB may be activated by active oxygen and brings about changes in gene expression that may lead to cell proliferation and the inhibition of apoptosis. We have hypothesized that environmental agents exert their hepatic tumor promoting activity at least in part by activating NF-kB. We found that phenobarbital, the PCBs 3,3’,4,4’-tetrachlorobiphenyl (PCB-77) and 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB-153), and several peroxisome proliferators activate NF-kB in the liver. We have several lines of evidence to support our hypothesis that the activation by peroxisome proliferators is mediated by oxidative stress produced by these agents. We also have examined if the activation of NF-kB is necessary for changes in cell proliferation and apoptosis from environmental agents. For these studies, we used mice that are deficient in the p50 subunit of NF-kB. We have observed that these p50 knockout mice (p50 -/-) do not have increased cell proliferation in response to peroxisome proliferators and PCBs, which is observed in wild-type mice. In addition, the p50 -/- mice have higher levels of hepatic apoptosis, which is decreased by the administration of peroxisome proliferators or PCBs. Finally, we found that the induction of hepatic tumors is inhibited in p50 -/- mice.

We are also examining if nutrition, especially dietary antioxidants, influences the promoting activity of environmental chemicals. We have found that dietary vitamin A, but not vitamin E or selenium, inhibits the promotion of hepatocarcinogenesis by PCBs. We recently demonstrated that several antioxidant phytochemicals inhibit the promoting activity of PCBs.

In another project, we are examining if cigarette smoke activates NF-kB and/or other transcription factors in the lung. We plan to then examine which dietary factors can inhibit the activation of these transcription factors by cigarette smoke.

Publications:

1. Tharappel, J.C., E.Y. Lee, L.W. Robertson, B.T. Spear, and H.P. Glauert. Regulation of cell proliferation, apoptosis, and transcription factor activities during the promotion of liver carcinogenesis by PCBs. Toxicol. Appl. Pharmacol. 179:172-184, 2002. http://linkinghub.elsevier.com/retrieve/pii/S0041008X01993603
2. Fadhel, Z., Z. Lu, L.W. Robertson, and H.P. Glauert. Effect of 3,3',4,4'-tetrachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl on the induction of hepatic lipid peroxidation and cytochrome P-450 associated enzyme activities in rats. Toxicology 175:15-25, 2002.
http://linkinghub.elsevier.com/retrieve/pii/S0300483X02000860

3. O’Brien, M.L., M.L. Cunningham, B.T. Spear, and H.P. Glauert. Peroxisome proliferators do not activate the transcription factors AP-1, early growth response-1 (Egr-1), or heat shock factors 1 and 2 (HSF1/2) in rats or hamsters. Toxicol. Sci. 69:139-148, 2002.
http://toxsci.oxfordjournals.org/cgi/content/full/69/1/139

4. Calfee-Mason, K.G., B.T. Spear, and H.P. Glauert. Vitamin E inhibits hepatic NF-kB activation in rats administered the hepatic tumor promoter, phenobarbital. J. Nutr. 132:3178-3185, 2002.
http://jn.nutrition.org/cgi/content/full/132/10/3178

5. Espandiari, P., H.P. Glauert, H.J. Lehmler, E.Y. Lee, C. Srinivasan, and L.W. Robertson. Polychlorinated biphenyls (PCBs) as initiators in liver carcinogenesis: resistant hepatocyte model. Toxicol. Appl. Pharmacol. 186:55-62, 2003.
http://linkinghub.elsevier.com/retrieve/pii/S0041008X02000182

6. Lu, Z., J.C. Tharappel, E.Y. Lee, L.W. Robertson, B.T. Spear, and H.P. Glauert. Effect of a single dose of polychlorinated biphenyls (PCBs) on hepatic cell proliferation and DNA binding activity of NF-kB and AP-1 in rats. Molec. Carcinog. 37:171-180, 2003.
http://dx.doi.org/10.1002/mc.10135

7. Tharappel, J.C., A. Nalca, A.B. Owens, L. Ghabrial, E.C. Konz, H.P. Glauert, and B.T. Spear. Cell proliferation and apoptosis are altered in mice deficient in the NF-kB p50 subunit after treatment with the peroxisome proliferator ciprofibrate. Toxicol. Sci. 75:300-308, 2003.
http://toxsci.oxfordjournals.org/cgi/content/full/75/2/300

8. Espandiari, P., H.P. Glauert, H.-J. Lehmler, E.Y. Lee, C. Srinivasan and L.W.Robertson. Initiating activity of 4-chlorobiphenyl metabolites in the resistant hepatocyte model. Toxicol. Sci. 79:41-46, 2004.
http://toxsci.oxfordjournals.org/cgi/content/full/79/1/41

9. Calfee-Mason, K.G., B.T. Spear, and H.P. Glauert. Effects of vitamin E on the NF-kB pathway in rats treated with the peroxisome proliferator, ciprofibrate. Toxicol. Appl. Pharmacol. 199:1-9, 2004.
http://linkinghub.elsevier.com/retrieve/pii/S0041008X04001632

10. Lu, Z., E.Y. Lee, L.W. Robertson, H.P. Glauert, and B.T. Spear. Effect of 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB-153) on hepatocyte proliferation and apoptosis in mice deficient in the p50 subunit of the transcription factor NF-kB. Toxicol. Sci. 81:35-42, 2004.
http://toxsci.oxfordjournals.org/cgi/content/full/81/1/35

11. Espandiari, P., L.W. Robertson, C. Srinivasan, and H.P. Glauert. Comparison of different initiation protocols in the resistant hepatocyte model. Toxicology 206:373-381, 2005.
http://linkinghub.elsevier.com/retrieve/pii/S0300-483X(04)00421-4

12. Glauert, H.P., Lu, Z., A. Kumar, R.P. Bunaciu, S. Patel, J.C. Tharappel, D.N. Stemm, H.J. Lehmler, E.Y. Lee, L.W. Robertson, and B.T. Spear. Dietary vitamin E does not inhibit the promotion of liver carcinogenesis by polychlorinated biphenyls in rats. J. Nutr. 135:283-286, 2005.
http://jn.nutrition.org/cgi/content/full/135/2/283

13. O’Brien, M.L., B.T. Spear, and H.P. Glauert. Role of oxidative stress in peroxisome proliferator-mediated carcinogenesis. Crit. Rev. Toxicol. 35:61-88, 2005. link

14. Glauert, H.P., A. Eyigor, J.C. Tharappel, S. Cooper, E.Y. Lee, and B.T. Spear. Inhibition of hepatocarcinogenesis by the deletion of the p50 subunit of NF-kB in mice administered the peroxisome proliferator Wy-14,643. Toxicol. Sci. 90:331-336, 2006.
http://toxsci.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16434500