Kevin Mark, Ph.D.

Kevin received his Ph.D. from the Department of Biochemistry and Biophysics at the University of California, San Francisco. As a graduate student in the laboratory of David Toczyski, he developed the approach of “ligase trapping” – a technique for identifying ubiquitylated proteins where ubiquitin-binding domains are fused to E3 ligases to delay substrate dissociation and degradation.

Kevin then joined the laboratory of Michael Rape as a postdoctoral fellow at the University of California, Berkeley. Here, his work revealed two novel ubiquitin-dependent pathways essential for maintaining embryonic stem cell pluripotency. First, he helped discover that a mitotic ubiquitin ligase reactivates transcription after each cell division – a critical mechanism of stem cell self-renewal. Later in his postdoctoral career, Kevin found that orphan protein quality control plays a fundamental role in maintaining the stem cell state. He showed that spent transcription factor complexes are dismantled and the individual subunits released must be marked for degradation by ubiquitin to facilitate proper gene expression. 

In 2024, Kevin joined the Department of Cell Biology at UT Southwestern Medical Center. His laboratory will continue to investigate and understand how ubiquitylation regulates gene expression and how a failure of these control pathways contributes to developmental disorders and diseases, such as neurodegeneration and cancer.

• Cancer
• Gene expression
• Neurodegeneration
• Protein quality control
• Stem cells
• Ubiquitylation

Featured Publications

Orphan quality control shapes network dynamics and gene expression.

Mark KG, Kolla S, Aguirre JD, Garshott DM, Schmitt S, Haakonsen DL, Xu C, Kater L, Kempf G, Martínez-González B, Akopian D, See SK, Thomä NH, Rapé M, Cell 2023 Aug 186 16 3460-3475.e23

Assembly and function of branched ubiquitin chains.

Kolla S, Ye M, Mark KG, Rapé M, Trends Biochem Sci 2022 Sep 47 9 759-771

Ubiquitin-dependent regulation of transcription in development and disease.

Mark KG, Rape M, EMBO Rep 2021 Apr 22 4 e51078

Gene expression and cell identity controlled by anaphase-promoting complex.

Oh E, Mark KG, Mocciaro A, Watson ER, Prabu JR, Cha DD, Kampmann M, Gamarra N, Zhou CY, Rape M, Nature 2020 Mar 579 7797 136-140

Monitoring SARS-CoV-2 incidence and seroconversion among university students and employees: a longitudinal cohort study in California, June-August 2020.

Hunter LA, Wyman S, Packel LJ, Facente SN, Li Y, Harte A, Nicolette G, Di Germanio C, Busch MP, Reingold AL, Petersen ML, BMJ Open 2023 Apr 13 4 e063999

Blueprint for a pop-up SARS-CoV-2 testing lab.

Nat Biotechnol 2020 Jul 38 7 791-797

Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence.

Engström P, Burke TP, Mitchell G, Ingabire N, Mark KG, Golovkine G, Iavarone AT, Rape M, Cox JS, Welch MD, Nat Microbiol 2019 Dec 4 12 2538-2551

EMI1 switches from being a substrate to an inhibitor of APC/C^CDH1 to start the cell cycle.

Cappell SD, Mark KG, Garbett D, Pack LR, Rape M, Meyer T, Nature 2018 Jun 558 7709 313-317

Isolation of ubiquitinated substrates by tandem affinity purification of E3 ligase-polyubiquitin-binding domain fusions (ligase traps).

Mark KG, Loveless TB, Toczyski DP, Nat Protoc 2016 Feb 11 2 291-301

Prb1 Protease Activity Is Required for Its Recognition by the F-Box Protein Saf1.

Mark KG, Meza-Gutierrez F, Johnson JR, Newton BW, Krogan NJ, Toczyski DP, Biochemistry 2015 Jul 54 29 4423-6

• CPRIT Scholar - Recruitment of First-Time Tenure-Track Faculty
  (2024)
• The Welch Foundation Research Grant
  (2024)
• UT Southwestern Endowed Scholar
  (2023)
• NIH F32 Postdoctoral Individual National Research Service Award
  (2016)
• NSF Graduate Research Fellowship, Honorable Mention
  (2009)

• Harold C. Simmons Comprehensive Cancer Center (2024)