Michael Ihnat, Ph.D.

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Summary

A main focus of the Ihnat laboratory research is on micrometastatic tumor ‘dormancy,’ the period from when micrometastatic cancer cells sit down in the secondary organ/site to the time in which they reactivate. We also have studied the environmental toxicology of metals, arsenic and chromium in particular, for many years and we have recently developed a collaborative project looking at the nephrotoxicity of water-soluble components of lignite coal in drinking water. The Ihnat Laboratory Our research is focused on preclinical drug development, with a particular emphasis on anticancer therapies. We collaborate extensively with Dr. Randy Gallucci and his immunotoxicology/immunopharmacology team, as well as several other members of the Pharmaceutical Sciences Department, on drug chemistry, formulation, delivery, pharmacokinetics, efficacy, and toxicity testing, in addition to animal imaging. Examples of Ongoing Research Projects: 1. Repurposing Cytotoxic Anticancer Drugs as Immunogenic Cell Death (ICD) Inducers. We are investigating whether FDA-approved anticancer drugs can act as ICD inducers in triple-negative breast cancer (TNBC) and bladder cancer, using both cell culture and animal models. ICD refers to a form of cell death that triggers the immune system, potentially enhancing the body's ability to fight tumors. Our research explores the possibility of combining these ICD inducers with immune checkpoint inhibitor drugs, such as PD-1 inhibitors, to better stimulate the immune system and improve tumor treatment. Additionally, we are studying the specific types of ICD induced by these drugs and seeking methods to amplify these effects without increasing toxicity to the patient. 2. Preclinical Drug Testing. Our lab studies the mode and mechanism of action, efficacy, safety pharmacology, and toxicology of new drugs in development. We use cellular and animal models to assess the safety and effectiveness of these drugs before they progress toward clinical trials. Our overall lab goal is to contribute to the development of more effective, less toxic drug treatments.

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Research

Tumor dormancy. Projects in this area include determining the role of aspects of the immune system in dormancy/reactivation, identifying drugs to target dormant cells and modeling aspects of dormancy/reactivation in culture and in animals. We collaborate with many folks including Drs. Randle Gallucci and Lucila Garcia-Contreras in the OU College of Pharmacy; Dr. Jeff Eckert in the Department of Pediatrics/Neonatology; Dr. Aleem Gangjee at Duquesne University; Dr. Pui-Kai Li at The Ohio State; and Drs. David Warshawsky, Robert Hurst and others at Vuja De Sciences, a company devoted to studying tumor dormancy.

Lignite coal nephrotoxicity. We have been working with two geologists, Dr. R. Paul Philp at The University of Oklahoma in Norman, and Dr. Ann Ojeda at Auburn University to examine the nephrotoxic components of a low-rank coal called lignite, found in the gulf region of the US and the Balkan areas of europe. These components can leach into drinking water, particularly in private wells, and we have shown that lignite extracts are toxic to kidney cells in culture. Ongoing studies are examining the nephrotoxicity of these extracts in the drinking water in animals and determining which specific components of the extracts are nephrotoxic.

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Publications & Presentations

1. Yu P, Zhu H, Bosholm C C, Beiner D, Duan Z, Shetty A K, Mou S S, Kramer P A, Barroso L F, Liu H, Cheng K, Ihnat M, Gorris M A, Aloi J A, Woldemichael J A, Bleyer A, Zhang Y. Precision nephrotoxicity testing using 3D in vitro models. Cell & bioscience. 2023; 13 : 231

2. Sharma H, Sharma P, Urquiza U, Chastain L R, Ihnat M. Exploration of a Large Virtual Chemical Space: Identification of Potent Inhibitors of Lactate Dehydrogenase-A against Pancreatic Cancer. Journal of chemical information and modeling. 2023

3. Ding H, George S, Leng X I, Ihnat M, Ma J X, Jiang G, Margolis D, Dumond J, Zhang Y. Silk fibers assisted long-term 3D culture of human primary urinary stem cells via inhibition of senescence-associated genes: Potential use in the assessment of chronic mitochondrial toxicity. Materials today. Advances. 2022; 15

4. Ding H, Jambunathan K, Jiang G, Margolis D M, Leng I, Ihnat M, Ma J X, Mirsalis J, Zhang Y. 3D Spheroids of Human Primary Urine-Derived Stem Cells in the Assessment of Drug-Induced Mitochondrial Toxicity. Pharmaceutics. 2022; 14

5. Dib P, Zhang Y, Schalo I, Durand C, Ihnat M, Gallucci R, Standifer K M. TNF-α initiates allodynia and anxiety-like symptoms in a preclinical model of PTSD and co-morbid pain. Cellular and Molecular Neurobiology . 2021; 12 : 721999

Grants

1. A Novel Small Molecule for The Prevention and Treatment of Diabetic Retinopathy. HHS. Start Date: 2022. End Date: 2024.

2. Development of a Novel Class of LDH inhibitors for pancreatic cancer. HHS. Start Date: 2022. End Date: 2024.

3. Experimental and computational studies to identify optimal conditions for immune-cytotoxic combination therapy. State Agency. Start Date: 2022. End Date: 2024.

4. Nephrotoxic mechanisms of low-rank coal (lignite) leachates in drinking wate. NIH. Start Date: 2020. End Date: 2023.

5. Development of Small Molecules Targeting Cancer Metabolism. NIH. Start Date: 2019. End Date: 2022.

Awards and Honors

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Education

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Administrative Assignments

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