SUMMARY
The research team of Andrew J. Haak, Ph.D., investigates the cellular and molecular mechanisms that initiate and propagate tissue fibrosis across multiple organs. These organs include lung, liver, skin and eye. Dr. Haak's team brings together very diverse skill sets in medicinal chemistry, molecular pharmacology and cellular physiology to investigate these processes. Using creative approaches to high-throughput screening, synthetic chemistry and drug repurposing, his team develops novel tools and therapies. The goal of his research is to understand and potentially treat idiopathic pulmonary fibrosis (IPF), nonalcoholic steatohepatitis (NASH) and proliferative vitreoretinopathy (PVR).
Focus areas
- NF-kB signaling in IPF and aging. The NF-kB protein complex regulates transcription of inflammatory and pro-fibrotic secretory factors that promote multiple age-related diseases, including IPF. Dr. Haak's team is focused on identifying and characterizing regulators of NF-kB signaling in the context of aging and lung fibrosis and developing novel therapies to target this program.
- Cell population-specific anti-fibrotics. Multiple signaling pathways that regulate activation of mesenchymal cells in fibrotic diseases are also critical for regeneration or homeostasis of other resident cell types. This creates a challenge in developing therapies that target these pathways. Dr. Haak's team is currently developing YAP and TAZ, NF-kB, and multikinase inhibitors as anti-fibrotics that target specific populations of cells.
- GPCR signaling in fibrosis. G protein-coupled receptors (GPCRs) are the target of approximately 30% of all clinically approved drugs, making them an ideal class of proteins for drug and target repurposing efforts. Dr. Haak's research group is actively developing a D2 dopamine receptor antagonist for the treatment of PVR and a D1 dopamine receptor agonist for the treatment of IPF. His team also is investigating the potential of targeting orphan GPCRs in multiple fibrotic diseases.
Significance to patient care
By some estimates, 45% of deaths in the United States can be attributed to diseases where fibrosis plays a major role. Despite this massive burden there are very few clinically approved anti-fibrotic drugs. Dr. Haak's investigators are using their broad expertise to rapidly identify, design, develop and validate novel therapies hoping to treat this family of diseases.
Professional highlights
- Brewer Family Career Development Award in Support of Idiopathic Pulmonary Fibrosis and Related Interstitial Lung Disease Research, Mayo Clinic, 2021-2024.
- Innovation Accelerator Award, Office of Translation to Practice, Mayo Clinic, 2023.
- Catalyst Award, American Lung Association, 2019-2021.
- Discovery Award, Boehringer Ingelheim, 2019-2021.
- PFF Scholars, Pulmonary Fibrosis Foundation, 2019-2021.