John D. Imig, PhD
- Pharmacology and Toxicology
BA, Biology, Blackburn College, 1985
The Imig laboratory is dedicated to understanding the mechanisms by which certain fatty acids “eicosanoids” influence kidney and cardiovascular function. Research in the laboratory focuses on kidney and blood vessel function in normal and disease states. We have developed novel eicosanoid-based drugs to treat diseases including hypertension, stroke, heart attacks, diabetes, and kidney diseases. These novel drugs have tremendous potential as a therapy for cardiovascular and kidney diseases.
Hypertension, Diabetes, & Metabolic Syndrome
Obesity, hypertension, and type 2 diabetes are major contributing factors to the increase in the number of patients that have cardiovascular events and end-organ damage. Metabolic syndrome is a serious health problem worldwide that has two major underlying causes, abdominal obesity and insulin resistance that clusters with other cardiovascular risk factors. Endothelial dysfunction, inflammation, oxidative stress, and insulin resistance are interrelated and increase the risk for cardiovascular events and end-organ damage in hypertension, diabetes, and metabolic syndrome. Moreover, eicosanoids are altered in these diseases and contribute to endothelial function, inflammation, oxidative stress, and insulin resistance. In particular, cyclooxygenase (COX), epoxygenase, and soluble epoxide hydrolase (sEH) metabolites are altered in disease states and contribute to the progression of disease processes. We have identified a distinct synergy between COX-2 and sEH inhibitors on the eicosanoid metabolome. This finding resulted in the development and synthesis of COX-2/sEH inhibitors that demonstrate great promise as a novel therapeutic approach for treating hypertension, diabetes, and metabolic syndrome. The goals of this project will identify novel ways to therapeutically target the eicosanoid metabolome for improving cardiovascular, renal, and pancreatic function in hypertension, diabetes, and metabolic syndrome.
Chronic Kidney Disease (CKD)
CKD from any cause is a serious public health problem; an estimated 33 million Americans have kidney disease. Hypertension, obesity, diabetes, infections, and genetic disease can lead to CKD. Other at risk groups include veterans and first-responders exposed to radiation, either on the battlefield, from terrorist events, or as a result of industrial accidents; these people risk developing radiation nephropathy and ultimately CKD. CKD also occurs in 15% of hematopoietic stem cell transplant (HSCT) patients, and has been clearly linked to irradiation at the time of the HSCT. HSCT is increasingly used worldwide for the treatment of cancer, and over 50,000 people per year now undergo HSCT. Long-term survival after HSCT is now near 50%, which means that more people will have late effects, which include CKD. CKD due to radiation also occurs after radionuclide therapy for cancer. Our laboratory has identified and developed epoxyeicosatrienoic acid (EET) analogs that show promise as a novel therapeutic approach for CKD. EET analogs have anti-inflammatory, anti-apoptotic, and anti-oxidative activities that will translate into a novel therapeutic for CKD. Consequently, we will test EET analogs as a new and better treatment for CKD.
Acute Kidney Injury (AKI)
Acute kidney injury (AKI), also known as, nephrotoxicity, occurs after exposure to drugs, other medical procedures, or exogenous toxins. The mortality rate for AKI patients is 30-60% and 20-30% of the survivors of AKI will develop CKD. There are limited options for treating AKI and these options currently include fluid and blood pressure management via drugs and intravenous fluids or hemodialysis. EETs have biological actions that implicate them as important contributors to kidney function. Over the past decade it has become increasingly apparent that EETs have a myriad of kidney actions and the overwhelming majority of these biological actions are kidney protective. Our innovation is based on the expected outcome that EET analogs have unique kidney actions that make them a novel target for developing treatments to prevent and treat AKI. Recent studies have demonstrated that EET analogs prevent AKI and renal damage that occurs with the anti-cancer drug cisplatin. This research project will identify novel ways to therapeutically target EETs for treating AKI.
(Imig JD.) EBioMedicine. 2021 Apr;66:103331 PMID: 33857907 PMCID: PMC8050865 SCOPUS ID: 2-s2.0-85104061350 04/16/2021
(Imig JD, Hye Khan MA, Burkhan A, Chen G, Adebesin AM, Falck JR.) Int J Mol Sci. 2021 Mar 10;22(6) PMID: 33801911 PMCID: PMC7998941 SCOPUS ID: 2-s2.0-85103862451 04/04/2021
(Klemens CA, Chulkov EG, Wu J, Hye Khan MA, Levchenko V, Flister MJ, Imig JD, Kriegel AJ, Palygin O, Staruschenko A.) Hypertension. 2021 Feb;77(2):582-593 PMID: 33390052 PMCID: PMC7856014 SCOPUS ID: 2-s2.0-85100070512 01/05/2021
(Imig JD.) EBioMedicine. April 2021;66 SCOPUS ID: 2-s2.0-85104061350 04/01/2021
(Walkowska A, Červenka L, Imig JD, Falck JR, Sadowski J, Kompanowska-Jezierska E.) Front Physiol. 2021;12:622882 PMID: 33584348 PMCID: PMC7876274 02/16/2021
(Maranto C, Udhane V, Jia J, Verma R, Müller-Newen G, LaViolette PS, Pereckas M, Sabharwal L, Terhune S, Pattabiraman N, Njar VCO, Imig JD, Wang L, Nevalainen MT.) Cancers (Basel). 2020 Nov 18;12(11) PMID: 33217941 PMCID: PMC7724566 SCOPUS ID: 2-s2.0-85096199725 11/22/2020
(Imig JD.) Clin Sci (Lond). 2020 10 30;134(20):2707-2727 PMID: 33095237 SCOPUS ID: 2-s2.0-85094684789 10/24/2020
(Lillich FF, Imig JD, Proschak E.) Front Pharmacol. 2020;11:554961 PMID: 33776749 PMCID: PMC7994619 03/30/2021
(Stavniichuk A, Savchuk O, Khan AH, Jankiewicz WK, Imig JD, Merk D.) Visnyk Kyivskoho Natsionalnoho Universytetu Imeni Tarasa Shevchenka Biolohiia. 2020;80(1):10-15 PMID: 33437972 PMCID: PMC7799440 01/14/2021
(Imig JD, Hye Khan MA, Zhao X.) Front Physiol. 2020;11:625353 PMID: 33343402 PMCID: PMC7744816 12/22/2020
(Stavniichuk A, Savchuk O, Khan AH, Jankiewicz WK, Imig JD.) Visnyk Kyivskoho Natsionalnoho Universytetu Imeni Tarasa Shevchenka Biolohiia. 2020;81(2):25-31 PMID: 33251532 PMCID: PMC7696638 12/01/2020
(Imig JD, Morisseau C.) Front Pharmacol. 2020;11:598858 PMID: 33071800 PMCID: PMC7544929 10/20/2020