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Lady Mastermind is one of three daughters of the late Jason Wyngarde, the original Mastermind. She had an intense hatred for her half-sister, Martinique, for reasons unknown.
Regan Wyngarde was behind Gambit's framing in Australia. Lady Mastermind, acting under the orders of Sebastian Shaw, used her telepathic illusionary powers to assassinate Viceroy. This plot was created by Sebastian Shaw to gain revenge against Sage, his prized former secretary. Tessa was placed inside the Hellfire Club, as a mole, for Charles Xavier, where the two had originally met and bonded.
In an attempt to make Sage work for Shaw again, Lady Mastermind placed her in a series of illusions. However, Sage received help from Lifeguard to fight the illusions that Regan had woven. Sage was able to turn Lady Mastermind's powers against herself, and as a result Regan was left catatonic in a public hospital located in Sydney, Australia.
Regan was one of few mutants that retained their superhuman powers after M-Day. Regan fell victim to scientists of the Fordyce Clinic who were trying to determine if a person could catch mutation like a disease. Cannonball and Iceman found a comatose Regan, along with a partially disassembled Karima Shapandar. She was finally awakened from her coma after her powers had been temporarily hijacked by Serafina.
Regan became part of Rogue's strike force/field team. Rogue made it clear to Regan that she was only wearing the X-Men uniform because she was found with nothing more then a white sheet. Soon afterwards, the team fought and defeated Pandemic. Pandemic infected Rogue with Strain 88, so Regan went with the team to Cable's island, Providence, to find a cure for her. While there they fought a monster called Hecatomb and defeated it.
When Rogue's team of X-Men went to one of Mystique's safehouses an intruder alarm later went off. The X-Men couldn't find anyone and Lady Mastermind later revealed that she had been working with the Marauders and was keeping them hidden from the X-Men.
Lady Mastermind was recruited to the Sisterhood of Mutants when Madelyne Pryor promised to resurrect her father.
After Professor X's death
In the aftermath of the conflict between the Avengers and the X-Men, Mystique and Sabretooth freed Lady Mastermind from the Raft with the purpose of reforming the Brotherhood, committing numerous heists, and using Lady Mastermind's illusions to incriminate the original X-Men, who had recently been brought through time to the present by Beast.