Brenda began her career in 1984, featuring in the music video of Billy Crystal's ‘You Look Marvelous.' She then made her first few TV appearances the following year, with brief roles in 'St. Elsewhere,' 'MacGyver,' and 'Cheers.'
Soon after, Brenda made her film debut as ‘Danielle’ in the 1986 independent film 'Weekend Warriors.' However, her first prominent role was as ‘Captain Deladier’ in the 1997 satirical military science-fiction/action film 'Starship Troopers.' She again starred in the 2004 installment 'Starship Troopers 2: Hero of the Federation,' but as ‘Sergeant Dede Rake,’ since ‘Captain Deladier’ had died in the original series.
Brenda appeared as ‘Desiree’ in the 1987 TV movie 'Kenny Rogers as The Gambler, Part III: The Legend Continues' and ‘Jones’ in four episodes of the 'ABC' horror–drama series 'Twin Peaks.'
In 1992, Brenda starred in the 'CBS' sitcom 'Scorch.' She was cast to play one of the main characters, ‘Allison King,’ in six episodes. However, unfortunately, the show was canceled after only three episodes were aired. She then starred as ‘Lauren Sutliffe’ in the TV movie 'Stepfather III.'
Brenda was cast as the lead ‘Dr. Sammy Helding’ in the 1994 science-fiction TV movie 'Island City.' In 1996, Brenda was seen as rich TV producer ‘Kathleen Isley,’ who was shown controlling her boyfriend (Matthew Fox as ‘Charlie Salinger’), in the second season of the 'Fox' teen and family drama 'Party of Five.'
That year, Brenda joined the cast of the eighth season of the 'NBC' sitcom 'Seinfeld,' as ‘Sue Ellen Mischke’ (regular). She played ‘Sally Sasser’ a TV producer of a fictional news show, in seven episodes of the 'ABC' drama 'Sports Night' (1998–2000). Her next recurring role (eight episodes) was as ‘Mrs. Carmen Mackoul’ in 'The WB' drama '7th Heaven' (2000–2002).
Brenda starred as ‘Dr. Helen Corey’ in a segment of the 2000 anthology dark comedy/horror film 'Terror Tract,’ titled 'Come to Granny.' She was ‘Susan Andrews,’ the lead, in the 2003 independent comedy 'Exposed.'
Brenda was seen in the brief recurring role of ‘Julia Brown’ in 'The WB' drama 'Everwood' (2002–2005), which was her first role as a deceased wife. Two of her other short recurring roles were those of ‘Marsha Palmer’ in the 'ABC' legal drama 'The Court' (2002) and ‘Iris’ in the 'FX' medical drama 'Nip/Tuck' (2003).
Brenda's acting skills were displayed through strong characters such as ‘Mary Ann Steed’ in the 2004 historical drama film 'The Work and the Glory,' therapist ‘Paula’ in the 2009 drama 'You,' teaching staff ‘Ellen Behr’ in the 2014 independent comedy 'Teacher of the Year,' and a wealthy matriarch named ‘Charlotte’ in the 2015 comedy 'The Leisure Class.'
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From 2004 to 2012, Brenda portrayed her breakthrough role, the deceased ‘Mary Alice Young,’ narrating from the grave, in all the episodes (except two) of the 'ABC' mystery comedy–drama 'Desperate Housewives.' Her performance brought her two 'Emmy Award' nominations, in 2011 and 2012. She also shared two 'Screen Actors Guild Awards,' in 2005 and 2006.
In 2006, Brenda reprised her 'The Work and the Glory' role in its third part and was seen as ‘Arlene Ridgeway’ in four episodes of the short-lived 'ABC' comedy series 'Help Me Help You.'
Brenda was signed to play ‘Ann Ewing,’ the third wife of ‘Bobby Ewing’ (played by Patrick Duffy), in the 'TNT' primetime soap 'Dallas,' which was the spin-off of the 'CBS' drama of the same name. However, previously, in 1987, Brenda had guest-appeared in the original series, as the character ‘Cliff's one-night-stand partner.
While filming for 'Dallas,' Brenda started her stint as a narrator in the 'Investigation Discovery' documentary series 'Blood Relatives.' She has continued with the documentary series to date.
In 2015, Brenda joined the cast of the third season of 'The CW' post-apocalyptic drama 'The 100,' as ‘Nia, Queen of the Ice Nation.’ That year, she became a producer with the short film 'I Did Not Forget You,' which won several awards at various festivals.
In 2016, she had a recurring role as ‘Ilene Stowe’ in the second season of the 'AMC' post-apocalyptic horror–drama 'Fear the Walking Dead.' Later, she began essaying the recurring role of ‘Lillian Luthor,’ the leader of 'Project Cadmus' and the secondary antagonist, in 'The CW' superhero drama 'Supergirl.'
In 2018, Brenda guest-appeared as ‘Nora Walker’ in the second season of the 'Netflix' series '13 Reasons Why.' Her character was made a regular in the following season. In 2019, Brenda announced her debut directorial venture, ‘#3 Normandy Lane,' which tells a funny yet heartwarming story about an army wife and a life-size cardboard cutout.
Brenda has a few stage credits, too. As a ‘Montana Shakespeare Company' member, She was cast as ‘Tamara’ in 'Titus Redux,' at ‘CTG's 'Kirk Douglas Theatre.' In Los Angeles, she had roles in the two 'Ovation'-nominated plays: 'Trevor,' staged at the ‘Circle X Theatre,’ and 'Tempest Redux' (voice role) at 'The Odyssey Theatre.'
In 2000, Brenda performed with the 'Millennium Choir' at the ‘Vatican’ and toured throughout Italy with composer Beppe Cantarelli, as one of his lead solo singers. She sang in Latin and Italian.
Brenda is a certified yoga instructor and fertility expert. She previously taught at the 'Mind/Body Institute’ of the ‘University of California, Los Angeles’ (UCLA). She is the founder of the 'Strong Yoga 4Women' program. Brenda has also developed the educational workshop 'The Four Fields of Fertility' and has founded the online course 'Soulful Conceptions.'
In 2005, Brenda became the national spokesperson for the 'American Fertility Association,' and in 2018, she became a spokesperson for 'Path2Parenthood,' which is the largest comprehensive patient advocacy group for potential LGBTQ parents. Brenda has launched a women's health campaign in collaboration with the drug company 'Pfizer.'
Brenda’s pioneering work on infertility and women's wellness has been rewarded with an ‘Honorary Doctorate’ by 'Yo San University.'