| 1989 |
Cloned RyR1/calcium release channel cDNA (PNAS 86:8683-8687). |
| 1992 |
Identified FKBP12 (calstabin1) as a subunit of the RyR1 channel (JBC 267: 9474-9477). |
| 1994 |
Functionally expressed recombinant RyR1 channels and demonstration that calstabin1 (FKBP12) stabilizes the closed state of the channel (i.e. prevents leak) (Cell 77: 513-523). |
| 1998 |
Discovered that calstabin1 is required for coupled gating between RyR1 channels, removel of calstabin1 results in uncoupled channels that are leaky (Science 281:818-821). |
| 2000 |
Discovered that RyR2 channels are leaky in failing hearts due to stress-induced loss of calstabin2 from the channel macromolecular complex (Cell 101:365-376). |
| 2003 |
Discovered that depletion of calstabin2 results in leaky RyR2 channels that cause exercise-induced sudden cardiac death, RyR2 channel mutations in patients cause stress-induced sudden death (Cell 113:829-840). |
| 2004 |
Demonstrated that a rycal small molecule prevents loss of calstabin2 from RyR2 channels and inhibits exercise induced arrhythmias and sudden cardiac death (Science 304:292-6). |
| 2005 |
Demonstrated that a rycal prevents heart failure progression after myocardial infarction and improves skeletal muscle function (PNAS 102:9607-9612). |
| 2005 |
Discovered that a phosphodiesterase in the RyR2 complex is required to prevent hyperphosphorylation of the channel, loss of calstabin2 and heart failure and arrhythmias (Cell 123:25-35). |
| 2009 |
Discovered leaky RyR1 channels in Duchenne muscular dystrophy and demonstration that a rycal inhibits muscle damage and improves exercise capacity (Nature Medicine 15:325-330). |
| 2010 |
Discovered that stress-induced nitrosylation/oxidation of RyR channels combined with PKA phosphorylation depletes channels of calstabin resulting in intracellular calcium leak that causes heart failure progression
(JCI 120: 4375-87 ; JCI 120: 4388-98). |
