Institute of Environmental Health Sciences
(313) 961-0014 / (313) 961-1069 (Phone)
(313) 577-0082 (Fax)
A. Research Interests
Project #1: Study on hypertension induced by epoxyeicosatrienoic acid (EET) metabolism of soluble epoxide hydrolase (sEH):
Arachidonic acids are biotransformed to epoxyeicosatrienoic acids (EETs) by arachidonic acid epoxygenases (e.g. CYP2C and 2J). The EETs have potent vasoactive properties. The EETs are hydrolyzed to dihydroxyeicosatrienoic acids (DHETs) by sEH, which induces hypertension.
Our laboratory developed 11,12- and 14,15-DHET (sEH and 20-HETE Availability of the ELISAs will greatly facilitate study of sEH-induced hypertension.
Project #2: Study on prostaglandin H2 synthase form 2 (PGHS-2, also called as cyclooxygenase form 2, COX-2)-induced mitochondrial DNA damage after exposure to environmental toxicants.
Project #3: Developments and studies on DNA and protein microarrays to screen effects of environmental toxicants on gene and protein expressions.
Project #4: Studies on prostate cancer biomarkers.
- Production of anti-peptide antibodies against cytochromes P450, US patent #5,866,688 (2/2/99)
- Assessment of oxidative stress in vivo, US patent #5,891,622 (4/6/99)
- Scientific vial storage box, US Design patent (D492194)
- Detection of hypertension using immunoreactive metabolic products, US patent #6,440,682 and 6,534,282 (2 divisional patents issued on 8/27/02 & 3/18/2003, respectively)
- Assessment of oxidant stress in vitro and in vivo, US patent #6,812,212 (11/2/04)
- Detection of hypertension using glucuronidated metabolic products� US patent #7,695,927 (4/13/10)
- DNA damage analysis using quantitative polymerase chain reaction analysis (pending)
- Chip production, hybridization, and data interpretation for antibody and protein microarrays (pending)
- Form-specific antibody production for cancer biomarkers, NAG-1, H6D and other TGF-beta subfamily (pending)
- Detection of hypertension using glucuronidated metabolic products: inhibitor screening tools (pending)
- National Research Service (NRS) Award, NIEHS, Area of Training: Xenobiotic effects on P450 expression. 1992-1993.
- SBIR Contract Phase I, N43-ES-31002, �Development of antibodies for drug-metabolizing enzymes�, 10/1/93-3/31/94.
- SBIR Grant Phase I, R43 DK47855, �Prostaglandin H synthase-2: purification and immunoassay�, 4/1/94 - 9/30/94.
- SBIR Contract Phase II, N44ES42002, �Development of antibodies for drug-metabolizing enzymes�, 9/30/94-9/30/97.
- SBIR Grant Phase II, R44-GM47634-02A1, �Immunoassay for non-enzymatic arachidonate derivative�, 9/5/95 - 2/28/97.
- SBIR Grant Phase I, R43 GM51135, �Molecular probes for an orphan eicosanoid pathway�, 8/1/95 - 6/30/96.
- SBIR Grant Phase II, R44DK47885. �Prostaglandin H synthase-2: purification and immunoassay�. 9/1/96 - 9/30/97.
- SBIR Grant Phase I, NIEHS, Co-I. �Genotoxicity assays with endogenous P450 activation�. 9/15/96-9/14/97.
- SBIR Contract Phase I, N43ES85430, �Immunoassays for metabolites of AA epoxygenases�, 6/1/98 � 1/31/99.
- SBIR Contract Phase I, N43ES95438, �Mutagenicity/genotoxicity assays with endogenous PGHS-2�, 8/1/99 � 7/31/00.
- NIH R15GM59595, Co-I."Role of cytochrome P450 in isoflavone metabolism", 9/30/99-9/29/02.
- SBIR Contract Phase I, N43ES15462, �Microarrays of X. laevis genes: a tool for Mol. Toxicology�, 2/1/01 - 10/31/01.
- SBIR Contract Phase II, N44ES05459, �Immunoassays for metabolites of AA epoxygenases�, 3/15/00 � 3/13/04.
- MI Life Sciences Corridor Fund GR180085, Co-I./Consultant. �Eukaryotic arsenic resistance�, 1/1/01-12/31/04.
- SBIR Grant Phase II, N44ES11251, �Mutagenicity/genotoxicity assays with endogenous PGHS-2�, 9/30/01 � 6/30/04.
- SBIR Contract Phase I, N43ES35506, �Targeted antibody microarrays: a tool for Toxicoproteomics�, 6/1/03-3/31/04.
- SBIR Grant Phase II, R44ES012124, �Microarrays of X. laevis genes: a tool for Mol. Toxicology�, 9/19/03 - 8/31/06.
- SBIR Grant Phase I, R43AA014535, �Fetal alcohol syndrome biomarkers by antibody microarray�, 9/15/03�8/31/2006.
- SBIR Contract Phase I, N43CN53306, �Antibody microarray for cancer detection� 10/1/05 � 9/31/2006.
- STTR Grant Phase I, R41CA105578, �A molecular signature of cell invasion in breast cancer�, 3/1/04 � 2/28/07.
- SBIR Grant Phase II, R44ES013805, �Targeted antibody microarrays: a tool for Toxicoproteomics�, 9/1/05 - 8/31/08.
- SBIR Phase I, N273200700012C, �Diagnostic ELISA to measure prostate cancer biomarker in serum� 9/17/07 - 9/14/08.
- SBIR Phase II, N273200800006C �Diagnostic ELISA to measure prostate cancer biomarker in serum� 9/30/08 - 9/29/11.
- Supplementary fund for SBIR Phase II, N273200800006C 9/30/09 - 9/29/11.
- SBIR Phase I, N273201000011C �Novel HTS for Gap Junctional Communication� 9/13/10 - 9/12/11.
- SBIR Phase I, N261201100073C "Site-specific antibodies for GlcNAcylated proteins in cancer" 9/15/11 - 6/14/12.
a. Selected Research Papers (since 1991)
- Identification of the ATP binding sites of the CPSase of the multifunctional protein CAD by affinity labeling with 5'-[p-(fluorosulfonyl)-benzoyl]adenosine. H. Kim, L. Lee and D. R. Evans (1991) Biochemistry 30, 10322-10329.
- The structural organization of the hamster multifunctional protein, CAD: controlled proteolysis, domains and linkers. H. Kim, R. Kelly & D. R. Evans (1992) J. Biol. Chem. 267, 7177-7184.
- Evidence for elevation of CYP2E1 mRNA levels in rat kidney following pyridine administration. H. Kim, S. G. Kim, M. Lee and R. Novak (1992) Biochem. Biophys. Res. Commun. 186, 846-853.
- Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression. H. Kim, D. Putt, S. Reddy, P.F. Hollenberg & R.F. Novak (1993) J. Pharmacol. Exp. Ther.267,927-936.
- Pyridine induction of rat renal cytochrome P4502E1: Immunohistochemical localization and quantification J. A. Hotchkiss, H. Kim, R. F. Novak and A. R. Dahl. (1995).Toxicol. Letters 78, 1-7.
- 3-Methylcholanthrene (3-MC) and pyridine (PY) effects on CYP1A1, 1A2 expression in rat renal tissue as monitored by PCR. H.Kim, S.Reddy and R.F. Novak. (1995) Drug Metab. Dispos. 23,818-824.
- Production of a form-specific, inhibitory antibody for rat P450 2B1 using a peptide antigen for a putative substrate binding site. J. Charnecki, D. Putt, E.Y. Kim, and H. Kim. (1995) Biochem. Biophys. Res. Commun. 216, 1024-1033.
- Cytochromes P450 are expressed in proliferating cells in Barrett's metaplasia. H.J. Hughes, M.A. Morse, H. Kim, P.F. Guengerich, P.B. Watkins, M. B. Orringer, & D. G. Beer. (1999) Neoplasia, 1,145-153.
- The metabolism of genistein by rat liver microsomes and recombinant human cytochrome P450 enzymes. E. S. Roberts-Kirchhoff, J. R. Crowley, P. F. Hollenberg, and H. Kim (1999) Chem. Res. Toxicol. 12, 610-616.
- Effect of calcium channel antagonists on rat cytochrome P-450 2B and 3A forms. R. C. Zangar, J. R. Okita, H. Kim, P. E. Thomas, A. Anderson, R. J. Edwards, D. L. Springer and R. T. Okita (1999) J. Pharmacol. Exp. Ther. 290, 1436-41.
- Differential induction of rat hepatic P450 3A, 2B and 2E1 in response to pyridine treatment. H. Kim, D.A. Putt, R.C. Zangar, C.R. Wolf, F.P. Guengerich, R.J. Edwards, P.F. Hollenberg, R.F. Novak (2001 )Drug Metab. Dispos. 29, 353-360.
- Cytochrome P450 3A conjugation to ubiquitin in a process distinct from classical ubiquitination pathway. R. C. Zangar, A. L. Kimzey, J. R. Okita, D. S. Wunschel, R. J. Edwards, H. Kim and R. T. Okita (2002) Mol. Pharmacol. 61, 892-904.
- Computational characterization of a series of eicosanoids. A. S. A. Gracon, S. J. Pernecky, M. C. Milletti, J.-A Park, Y. Yuan and H. Kim (2005) Letters in Drug Design & Discovery 2, 322-328.
- Global gene expression profiling unveils S100A8 and S100A9 as candidate markers in H-Ras-mediated human breast epithelial cell invasion. A. Moon, H.-Y. Yong, A. Dombkowski, D. Cukovic, S. Salagrama, D. Putt, D. Kaplan, H. Kim and H.-R. Kim Mol. Cancer Res. 6: 1544-1553 (2008).
b. Book Chapters
- E. S. Roberts-Kirchhoff, C. K. Kim, and H. Kim, Nitration of cytochrome C by peroxynitrite: A putative anti-apoptotic pathway mediated by prostaglandin H2 synthase and nitric oxide synthase. in Advances in Experimental Biology and Medicine: Eicosanoids and Bioactive Lipids in Cancer & Radiation Injury, 5. K. V. Honn, L. J. Marnett and C. Serhan (eds) Plenum Co. NY, NY. (2002).
c. Abstracts (Since 2006)
- Synthesis of fatty acid ethyl esters as biological markers for the diagnosis of Fetal Alcohol Syndrome. E. S. Roberts-Kirchhoff, V. Hornik-Rosinski, A. Ignagni, E. E. Cole, K. Fleischmann, Y. Yuan and H. Kim (2006) The Society of Toxicology (SOT) annual meeting, Abstract #1658.
- Competitive ELISA for fatty acid ethyl esters as biological markers for the diagnosis of Fetal Alcohol Syndrome. E. S. Roberts-Kirchhoff, J. Chun, V. Hornik-Rosinski, B. Jiang, Y. Yuan and H. Kim (2007) The SOT, Abstract #233.
- Drug metabolism response evaluated by antibody protein microarray in male Sprague-Dawley rats exposed to phenobarbital (PB), 1,4 dioxane (1,4-D), trichloroetylene (TCE), and ethanol (ETOH). D.R. Geter, L. Kan, D. J. Kaplan, S. Salagrama, A. A. Dombkowski, H. Kim, G. Bhaskar, and W. T. Stott (2008) The SOT annual meeting, Abstract #1595.
- Abnormally decreased levels of non-steroidal anti-inflammatory drug-activated gene (NAG)-1 and H6D polymorphism in lung cancer patients' sera. A. Joiakim, D. J. Kaplan, K. Onofrey, R. Hadad, D. G. Beer and H. Kim. (2009) The SOT, Abstract #1403.