Resat Cinar, Ph.D., M.B.A.

Fibrosis is a progressive, complex, and multifactorial disease process that can affect multiple organs and arise from diverse causes. It involves tissue injury, chronic inflammation, oxidative stress, cellular senescence, abnormal wound healing, and excessive extracellular matrix deposition. Fibrotic process ultimately leading to organ dysfunction, disability, and premature death. Despite its substantial health and economic burden, effective treatments for fibrotic diseases remain limited.

The mission of the Section on Fibrotic Disorders is to understand the cellular and molecular mechanisms that drive fibrosis and translate these discoveries into biomarkers, therapeutic targets, and effective treatments, with a primary focus on fibrosing lung diseases and the impact of alcohol use on lung health.

The Section integrates human translational research with preclinical disease models and multidisciplinary approaches in genomics, metabolomics, immunology, cell biology and metabolism, analytical chemistry, pharmacology, systems biology, and systems pharmacology. A major focus is the development of multi-target therapies designed to simultaneously address multiple disease-driving pathways through rational polypharmacology and combination therapy.

Current research areas include:

1. Therapeutic target identification and drug discovery in fibrotic lung diseases
   Investigating the cell-specific pathogenic roles of cannabinoid receptor 1 (CB1R) and the therapeutic potential of second- and third-generation peripherally restricted CB1R antagonists in idiopathic pulmonary fibrosis (IPF), Hermansky-Pudlak syndrome pulmonary fibrosis (HPSPF), and other forms of lung injury and fibrosis.
2. Biomarker discovery in fibrotic lung diseases
   Identifying diagnostic and prognostic biomarkers to detect disease earlier, track progression, stratify patients, and monitor response to therapy, with a particular focus on rare fibrosing lung diseases.
3. Alcohol and lung health
   Investigating how chronic alcohol consumption alters lung immunity and contributes to inflammation, tissue injury, susceptibility to secondary insults.

By linking mechanistic discoveries with human studies and preclinical models, the Section seeks to advance new approaches for earlier diagnosis, patient stratification, disease monitoring, and treatment of fibrotic lung diseases.

Resat Cinar received his B.Sc. in Pharmacy from Ege University Faculty of Pharmacy in Izmir, Turkey, in 2004. He subsequently received a fellowship to participate in the International Training Course in Biological Science at the Biological Research Center of the Hungarian Academy of Sciences in Szeged, Hungary. He earned a Ph.D. in Biological Sciences in 2010 from the University of Szeged, Hungary. He also earned an M.B.A. from the University of Szeged Faculty of Economics and Business Administration.

From 2005 to 2009, Dr. Cinar was a research associate at the Institute of Biochemistry of the Hungarian Academy of Sciences Biological Research Center, where he studied the molecular pharmacology of cannabinoid receptor 1 (CB1R) and opioid receptors. In 2010, he joined the Laboratory of Physiologic Studies at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for postdoctoral training with Dr. George Kunos, investigating the role of the endocannabinoid/CB1R system in metabolic regulation in obesity, diabetes, and fatty liver disease. In 2015, he became a staff scientist in the Laboratory of Physiologic Studies. In 2021, he was recruited as a tenure-track investigator and acting chief of the Section on Fibrotic Disorders.

In 2018, Dr. Cinar was among the recipients of the NIH NCATS Director's Award for scientific and medical achievement, recognizing extraordinary leadership in the discovery and development of a first-in-class peripheral CB1R antagonist for the treatment of metabolic syndrome. His research has demonstrated important pathogenic roles of the endocannabinoid/CB1R system in fibroproliferative disorders, including lung and liver fibrosis.

Dr. Cinar's research focuses on multi-targeting and functional selectivity as therapeutic strategies for developing more effective and safer treatments for fibrotic disorders. His work identified the simultaneous inhibition of CB1R and inducible nitric oxide synthase (iNOS) as a rational multi-target strategy for improving antifibrotic efficacy in fibrotic disorders, including pulmonary fibrosis. He has also contributed to the development, patenting, lead optimization, and selection of novel peripherally restricted hybrid compounds targeting CB1R/iNOS or CB1R/AMPK as third-generation CB1R antagonists with therapeutic potential in obesity, diabetes, and fibrotic disorders.

His research also contributed to the development of the first-in-class functionally biased peripheral CB1R antagonist MRI-1891 (monlunabant), which has therapeutic potential in diabetes and metabolic disorders and was designed to improve the safety and efficacy of CB1R antagonism through functional selectivity.

Dr. Cinar's research identified two lead compounds, MRI-1867 (zevaquenabant) and MRI-1891 (monlunabant), that demonstrated therapeutic efficacy in preclinical studies of fibrotic and metabolic disorders and have potential for translation from basic research to clinical applications. Both compounds have advanced to clinical-stage development.