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Dr Stein and his collaborators have 4 major areas of activity:
- Inflammation and cardiovascular disease: Using extensively characterized cohorts of patients with SLE, rheumatoid arthritis and controls we study the relationship between inflammation and coronary atherosclerosis (measured as coronary calcification) and cardiac structure and function (using MRI). We showed that oxidative stress in RA may modify HDL so that so that HDL is no longer protective against atherosclerosis; Michelle Ormseth has an Arthritis Foundation Clinical to Research Transition Award (2013-15) to study HDL function.
- Cardiovascular pharmacogenetics: We have defined the genetic determinants, particularly in adrenergic signaling pathways, of cardiovascular response using small homogeneous groups of subjects studied under tightly controlled conditions in the CRC. Current studies include platelet function studies and large studies in BioVU examining adre nergic receptor variants and patient responses.
- Drug metabolism pharmacogenetics: We showed that VKORC1 and CYP2C9 genetic variants affect initial responses to warfarin. Now, in BioVU we are examining the genetic contribution to the risk of bleeding during warfarin therapy. Additional studies target other drugs whose metabolism is affected by genetic variation including collaborations with Wes Ely’s group at Vanderbilt studying ICU drugs, and Ron Krauss’s group at CHORI studying statins.
- Drug Safety: We collaborate with Wayne Ray’s group to study drug safety, particularly sudden death, and also with Marie Griffin and Carlos Grijalva to study opioids and the risk of serious infections in older adults in large administrative databases. Cecilia Chung has a K award from NIAMS to study serious drug interactions.