(313) 972-8025 (fax)
AddressInstitute of Environmental Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201
Office Phone(313) 961-0014 / (313) 961-1069
Project #1: Study on hypertension- and cardiovascular disease-induced by metabolism of epoxyeicosatrienoic acid (EET) by soluble epoxide hydrolase (sEH): Funded by NIEHS SBIR contracts.
Arachidonic acid (AA) is biotransformed to EET by AA epoxygenases, CYP2C and 2J. The EET has potent vasoactive properties. The EET is hydrolyzed to inactive dihydroxyeicosatrienoic acid (DHET) by sEH.
Our laboratory found sEH-dependent hypertension (4 US patents) and developed ELISA and nanowell technologies to detect 14,15-DHET (sEH metabolite) in blood and urine (>80 articles have been published). Drug companies screened sEH inhibitors using the 14,15-DHET ELISA to develop drugs to treat hypertension, kidney disease and chronic obstructive pulmonary disease (COPD).
Project #2: Study on biomarkers to predict cancer therapy related cardiac dysfunction (CTRCD) in the area of Cardio-Oncology: Funded by NHLBI SBIR contract.
We found levels of 14,15-DHET (sEH metabolite) in blood are elevated prior to major changes in cardiac structure and function after exposure to anthracyclines, e.g., doxorubicin (DOX) (US patent pending). Early identification of patients susceptible to chemotherapy-induced cardiotoxicity could lead to targeted drug treatment and reduced cardiac impairment.
Project #3: Studies on biomarkers of lung, prostate and breast cancers:
1. Development of site-specific antibodies for O-GlcNAcylated proteins in cancer, e.g., Thr-58-O-GlcNAcylated c-myc and Ser-149-O-GlcNAcylated p53, that allow the identification of glycosylated biomarkers in cancer: Funded by NCI SBIR contracts.
2. Identification of early (Stage I) lung cancer miRNA biomarkers using qRT-PCR and novel label-free nanoarray technology: Funded by NCI SBIR contract.
3. Improvement of prostate cancer diagnosis using a multiplex test of PSA, GDF-15 (NAG-1) and glycan-binding auto-IgG in plasma: Funded by NCI SBIR grant.
Project #4: Development of mitochondrial DNA damage (funded by NIEHS SBIR grant) and copy number kits and 8-isoprostane oxidative stress ELISA. The 8-isoprostane ELISA was used to study differential 8-isoprostane levels in sewage wastewater effluents from metro Detroit communities.
Project #5: Development of sensitive and specific bisphenol A (BPA) ELISA and studies on differential BPA levels in sewage wastewater effluents from metro Detroit communities and BPA concentrations in liquid supernatants of imported canned foods.
"Production of anti-peptide antibodies against cytochrome P450", #5,866,688 (2/2/99); "Assessment of oxidative stress", #5,891,622 (4/6/99); “Detection of hypertension using immunoreactive metabolic products” #6,440,682 and 6,534,282 (8/27/02 & 3/18/2003); “Assessment of oxidant stress in vitro and in vivo”, #6,812,212 (11/2/04); “Detection of hypertension using glucuronidated metabolic products” #7,695,927 (4/13/10); “Detection of hypertension: inhibitor screening” #8,409,821 (4/2/13); “Chip production, data interpretation for antibody and protein microarrays” #8,765,641 (7/1/14); "Form-specific antibody for cancer biomarkers, NAG-1, H6D and other TGF-beta subfamily" #9,212,221 (12/15/15); “Glycosylated site-specific antibodies and anti-cancer compounds” #10,317,409 B2 (6/11/19), “Label-free nucleic acid biomarker detection in cancer and other diseases” (pending), “Early biomarkers of cardiotoxicity” (pending).
C. Funding (Selected out of 23)
National Research Service Award (NRSA), NIEHS, Xenobiotic effects on P450 expression.
NIEHS SBIR Contract Phases I and II, “Immunoassays for metabolites of AA epoxygenases”.
NIEHS SBIR Contract Phases I and II, “Mutagenicity/genotoxicity assays with endogenous PGHS-2”.
NIGMS, R15, Co-I. "Role of cytochrome P450 in isoflavone metabolism".
NIEHS SBIR Contract Phases I and II “Targeted antibody microarrays: A tool for Toxicoproteomics.
NIEHS SBIR Phases I and II “Diagnostic ELISA for prostate cancer biomarker in serum”
NCI SBIR Phases I and II "Site-specific antibodies for proteins in cancer"
NCI SBIR Phase I "Glycoproteins: Biomarkers for cancer and inflammatory diseases".
University of Oslo European grant "Site-specific antibodies for proteins in prostate cancer".
NCI SBIR Phase I "Circulating nucleic acid label-free nanoarray in cancer".
State of Michigan, Small Company Innovation program (SCIP) “Micro- and Nanowell Fabrication”.
NHLBI SBIR Phase I "Label-free nano tech for early cardiotoxicity biomarkers”.
DepartmentInstitute of Environmental Health Sciences
a. Selected Research Papers
Simmer JP, Kelly RE, Rinker AG Jr, Zimmermann BH, Scully JL, Kim H, Evans DR. Mammalian dihydroorotase: nucleotide sequence, peptide sequences, and evolution of the dihydroorotase domain of the multifunctional protein CAD. Proc Natl Acad Sci U S A. 1990 87:174-178. doi: 10.1073/pnas.87.1.174.
Kim HS, Lee L, Evans DR. Identification of the ATP binding sites of the carbamyl phosphate synthetase domain of the Syrian hamster multifunctional protein CAD by affinity labeling with 5'-[p-(fluorosulfonyl)benzoyl]adenosine. Biochemistry. 1991 30:10322-10329. DOI: 10.1021/bi00106a033.
Kim H, Kelly RE, Evans DR. The structural organization of the hamster multifunctional protein CAD. Controlled proteolysis, domains, and linkers. J Biol Chem. 1992 267:7177-7184. PMID: 1348059.
Kim H, Kim SG, Lee MY, Novak RF. Evidence for elevation of cytochrome P4502E1 (alcohol-inducible form) mRNA levels in rat kidney following pyridine administration. Biochem Biophys Res Commun. 1992 186:846-853. doi: 10.1016/0006-291x(92)90823-4.
Kim H, Putt D, Reddy S, Hollenberg PF, Novak RF. Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression. J Pharmacol Exp Ther. 1993 Nov;267(2):927-36. PMID: 8246169.
Hotchkiss JA, Kim H, Hahn FF, Novak RF, Dahl AR. Pyridine induction of Sprague-Dawley rat renal cytochrome P4502E1: immunohistochemical localization and quantitation. Toxicol Lett. 1995 78:1-7. doi: 10.1016/0378-4274(94)03223-t.
Kim H, Reddy S, Novak RF. 3-Methylcholanthrene and pyridine effects on CYP1A1 and CYP1A2 expression in rat renal tissue. Drug Metab Dispos. 1995 23:818-824. PMID: 7493548.
Charnecki J, Putt D, Kim EY, Kim H. Production of a form-specific, inhibitory antibody against rat cytochrome P450 2B1 using a synthetic peptide antigen against a putative substrate binding site. Biochem Biophys Res Commun. 1995 216:1024-1033. doi: 10.1006/bbrc.1995.2723.
Hughes SJ, Morse MA, Weghorst CM, Kim H, Watkins PB, Guengerich FP, Orringer MB, Beer DG. Cytochromes P450 are expressed in proliferating cells in Barrett's metaplasia. Neoplasia. 1999 1:145-153. doi: 10.1038/sj.neo.7900017.
Roberts-Kirchhoff ES, Crowley JR, Hollenberg PF, Kim H. Metabolism of genistein by rat and human cytochrome P450s. Chem Res Toxicol. 1999 12:610-616. doi: 10.1021/tx9802320.
Zangar RC, Okita JR, Kim H, Thomas PE, Anderson A, Edwards RJ, Springer DL, Okita RT. Effect of calcium channel antagonists nifedipine and nicardipine on rat cytochrome P-450 2B and 3A forms. J Pharmacol Exp Ther. 1999 290:1436-1441. PMID: 10454523.
Kim H, Putt DA, Zangar RC, Wolf CR, Guengerich FP, Edwards RJ, Hollenberg PF, Novak RF. Differential induction of rat hepatic cytochromes P450 3A1, 3A2, 2B1, 2B2, and 2E1 in response to pyridine treatment. Drug Metab Dispos. 2001 29:353-360. PMID: 11181506.
Zangar RC, Kimzey AL, Okita JR, Wunschel DS, Edwards RJ, Kim H, Okita RT. Cytochrome P450 3A conjugation to ubiquitin in a process distinct from classical ubiquitination pathway. Mol Pharmacol. 2002 61:892-904. doi: 10.1124/mol.61.4.892. Erratum in: Mol Pharmacol. 2003 63:1198.
Roberts-Kirchhoff ES, Kim CK, Kim H. Nitration of cytochrome C by peroxynitrite: A putative anti-apoptotic pathway by PGHS and NOS. 2002 in Eicosanoids and Bioactive Lipids in Cancer, 5. K. V. Honn, Plenum Co. NY, NY.
Gracon ASA, Pernecky SJ, Milletti MC, Park J-A, Yuan Y, Kim H. Computational characterization of a series of eicosanoids. Letters in Drug Design & Discovery 2005 2: 322-328.
Moon A, Yong HY, Song JI, Cukovic D, Salagrama S, Kaplan D, Putt D, Kim H, Dombkowski A, Kim HR. Global gene expression profiling unveils S100A8/A9 as candidate markers in H-ras-mediated human breast epithelial cell invasion. Mol Cancer Res. 2008 6:1544-1553. doi: 10.1158/1541-7786.
Santos JM, Jurban M, Kim H. Could sewage epidemiology be a strategy to assess lifestyle and wellness of a large scale population? Med Hypotheses. 2015 85:408-411. doi: 10.1016/j.mehy.2015.06.020.
Santos JM, Park JA, Joiakim A, Putt DA, Taylor RN, Kim H. The role of soluble epoxide hydrolase in preeclampsia. Med Hypotheses. 2017 108:81-85. doi: 10.1016/j.mehy.2017.07.033.
Bae SH, Park JH, Choi HG, Kim H, Kim SH. Imidazole Antifungal Drugs Inhibit the Cell Proliferation and Invasion of Human Breast Cancer Cells. Biomol Ther (Seoul). 2018 26:494-502. doi: 10.4062/biomolther.2018.042.
Joiakim A, Kaplan D, Santos JM, Friedrich K, Putt DA, Kim S-H, Kim H. Bisphenol A (BPA) in Liquid Portions of Canned Foods Obtained from Domestic and Asian Markets in the United States. Environ Dis 2019 4:6-11.
Dos Santos JM, Joiakim A, Kaplan DJ, Putt DA, Perez Bakovic G, Servoss SL, Rybicki BA, Dombkowski AA, Kim H. Levels of plasma glycan-binding auto-IgG biomarkers improve the accuracy of prostate cancer diagnosis. Mol Cell Biochem. 2021 476:13-22. doi: 10.1007/s11010-020-03876-7.
Santos JM, Joiakim A, Putt DA, Scherrer-Crosbie M, Kim H.14,15-Dihydroxyeicosatrienoic acid, a soluble epoxide hydrolase metabolite in blood, is a predictor of chemotherapy-induced cardiotoxicity in breast cancer. 2021 Manuscript submitted.
b. Abstracts (Since 2017)
Inhibition of pro-hypertensive soluble epoxide hydrolase (sEH) activity by honokiol, a component of magnolia bark. Santos JM, Joakim A, Putt D, Utterbeck K, Curtis B, Kaplan D, Putt D, Kim H. 2017 The SOT, Abstract #2601.
Identification of early lung cancer miRNA biomarkers using qRT-PCR and novel nanoarray technology. Santos JM, Joiakim A, Putt D, Herrera-Fierro P, Ray V, Dombkowski A, Chen G, Beer DG, Kim H. 2017 AACR Abstract #5436.
Serum 14,15-DHET, a metabolite of soluble epoxide hydrolase, is an early biomarker to predict doxorubicin (DOX)-induced cardiotoxicity in rats. Santos JM, Putt DA, Kaplan D, Joiakim A, Kim H. 2018 https://www.toxicology.org/pubs/docs/Tox/2018Tox.pdf The SOT Abstract #1258, Page 62.
14,15-DHET, a metabolite of soluble epoxide hydrolase (sEH), is an early biomarker of doxorubicin-induced cardioxicity. Putt DA, Santos JM, Joiakim A, Kaplan DJ, Scherrer-Crosbie M, Kim H. 2018 The 17th International Eicosanoid Conference, Abstract #CV-17, Cardiovascular.
Improvement of prostate cancer diagnosis using a multiplex test of PSA, GDF-15 (NAG-1) and glycan-binding auto-IgG in plasma. Kim H, Santos JM, Joiakim A, Kaplan DJ, Dombkowski A, Rybicki B, Putt DA 2018 AACR, Abstract #690.
Inhibition of pro-hypertensive soluble epoxide hydrolase (sEH) activity by magnolia bark extract in a one-step inhibition 14,15-DHET ELISA. Joiakim A, Santos J, Putt D, Jeon P, Kaplan D, Kim H. 2019 https://www.toxicology.org/pubs/docs/Tox/2019Tox.pdf The SOT Abstract #2687, Page 397.
Differential levels of 2-naphthol, a urinary biomarker of exposure to air pollution, in sewage wastewater effluents from metro Detroit communities. Joiakim A, Santos JM, Jeon P, Kaplan D, Jurban M, Friedrich K, Kim H. 2020 https://www.toxicology.org/pubs/docs/Tox/2020ToxSup.pdf The
SOT Late-breaking abstract #3577, Page 202.