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Samantha Mack has a diverse work experience spanning multiple fields. Samantha began their career at IBM as a Financial Analyst from 2000 to 2001. Samantha then transitioned into the medical field and worked as a Resident Physician at the University of Colorado Health Sciences Center from 2007 to 2011. After that, Samantha held roles as a Fellow at Children's Hospital Boston from 2011 to 2012, and at the University of Colorado & Bonfils Blood Center from 2012 to 2013. Following these fellowships, they worked as a Pathologist at Unipath PC from 2013 to 2017. Currently, Samantha is working as a Medical Director at Vitalant, a role they have held since 2017.

Samantha Mack completed their Bachelor's degree in French and Finance at Doane University from 1996 to 1999. Samantha further pursued their education at the University of Nebraska College of Medicine, where they obtained an MD degree in Medicine from 2003 to 2007.