Our lab focuses on therapeutically targeting nitric oxide (NO) and cyclic guanosine monophosphate (GMP) signaling in a variety of disorders. Current research topics include:
- Elucidating the molecular mechanisms underlying the strain- and gender-specific hypertension associated with impaired NO-cGMP signaling. This project includes the characterization of renin and 20-hydroxyeicosatetraenoic acid (20-HETE, in collaboration with Dr. Schwartzman) systems as blood-pressure modifying signaling mechanisms in a setting of impaired NO-cGMP signaling (e.g. in soluble guanylate cyclase (sGC)-deficient mice).
- Elucidating the role of impaired NO-cGMP signaling in the development of primary open angle glaucoma, a project led by Dr. Dordea. This project includes characterization of a new mouse model of glaucoma (in collaboration with Dr. Ksander, Dr. Gregory-Ksander, and Dr. Pasquale) and identifying biomarkers and therapeutic targets in clinically relevant samples (a collaboration with Dr. Ritch and Dr. Ozaki).
- Studying the role of sGC in the cardiotoxicity associated with use of doxorubicin (DOX), a potent chemotherapeutic agent, a project led by Dr. Vandenwijngaert.
- Using micro-RNA technology to modulate natriuretic peptide levels also a potential therapy for hypertension and heart failure, in collaboration with Dr. Newton-Cheh and Dr. Bloch.
- Physiologic profiling of genetic variants in the genes encoding sGC and natriuretic peptides (NPs), a project led by Dr. Newton-Cheh.
- Using emerging genomic information to characterize NO signaling in the Weddell seal (a collaboration with Dr. Zapol, Dr. Costa, Dr. Lindblad-toh, and Dr. Alföldi).
- Regulating cGMP signaling by microRNAs (miRs). This project aims to identify and therapeutically target miRs that regulate mRNAs encoding NO synthase, and soluble guanylate cyclase.
- In collaboration with investigators in Europe and the US, we are characterizing the role of NO-cGMP signaling in stroke, gastrointestinal motility, erectile function, renal function, skeletal muscle function, brain and lung development, and cardiac dysfunction associated with systemic inflammation. Furthermore, we are using sGC mutant mice to study the mechanisms underlying the ability of inhaled NO to attenuate injury associated with myocardial infarction and cardiac arrest (projects led by Dr. Ichinose).