Carlos J. Pérez Kerkvliet

Carlos Santos Pérez

Email: santo208@umn.edu

Entering Class:
 2014

Education:

University of Puerto Rico-Cayey
Biology major
B.S., 2014

University of Minnesota
Microbiology, Immunology and Cancer Biology Graduate Program
Ph.D., 2020

MSTP Student Governance:

  • Student Advisory Committee 2014-2016
  • Retreat Planning Committee, 2015
  • Student Admissions and Recruitment Committee, 2018-2020

Honors and Awards:

  • Ruth L. Kirschstein National Research Service Award for Predoctoral MD/PhD Fellows, National Cancer Institute, 2019-2022

Thesis Advisor: Carol Lange, Ph.D.

Hobbies and Interests:

  • Puerto Rican and United States politics
  • Running
  • Hiking

Thesis Research:

Therapeutic options for triple-negative breast cancer (TNBC) are limited. This subtype of breast cancer (BC) lacks expression of molecules currently exploited for targeted therapy, including steroid hormone receptors: estrogen receptor (ER) and progesterone receptor (PR), as well as human epidermal growth factor 2 receptor (HER2). TNBC is the most aggressive, metastatic, and deadly form of BC, and it accounts for 20-30% of all BC cases. Although lacking these receptors, there is an emerging role of the glucocorticoid receptor (GR) in promoting progression and chemotherapy resistance in TNBC. Our main objective is to understand the role of oncogenic molecular signaling associated with GR. Our preliminary data indicate that TGFβ and 14-3- 3ζ modulate the activity of the GR, presumably via phosphorylation and direct interaction. Notably, both TGFβ and 14-3- 3ζ have been shown to be elevated in TNBC. We hypothesize that TGFβ and 14-3- 3ζ act in concert with GR to promote oncogenesis. To address this hypothesis, we will identify the mechanisms of phospho-Ser134 GR and 14-3- 3ζ interactions in TNBC progression. Additionally, we will test whether phospho-Ser134 GR is critical for proliferation and metastasis of TNBC cells in vivo. This project is relevant to public health because phospho-Ser134 GR and its associated signaling factors are excellent drug targets and possible biomarkers that will assist in better detection, diagnosis and management of TNBC.

Publications (Pubmed):

Kerkvliet CP, Truong TH, Ostrander JH, Lange CA. Stress sensing within the breast tumor microenvironment: how glucocorticoid receptors live in the moment. Essays Biochem. 2021 Dec 17;65(6):971-983.

Truong TH, Benner EA, Hagen KM, Temiz NA, Kerkvliet CP, Wang Y, Cortes-Sanchez E, Yang CH, Trousdell MC, Pengo T, Guillen KP, Welm BE, Dos Santos CO, Telang S, Lange CA, Ostrander JH. PELP1/SRC-3-dependent regulation of metabolic PFKFB kinases drives therapy resistant ER+ breast cancer. Oncogene. 2021 Jun;40(25):4384-4397.

Mauro LJ, Seibel MI, Diep CH, Spartz A, Perez Kerkvliet C, Singhal H, Swisher EM, Schwartz LE, Drapkin R, Saini S, Sesay F, Litovchick L, Lange CA. Progesterone Receptors Promote Quiescence and Ovarian Cancer Cell Phenotypes via DREAM in p53-Mutant Fallopian Tube Models. J Clin Endocrinol Metab. 2021 Jun 16;106(7):1929-1955.

Dwyer AR, Perez Kerkvliet C, Krutilina RI, Playa HC, Parke DN, Thomas WA, Smeester BA, Moriarity BS, Seagroves TN, Lange CA. Breast tumor kinase (Brk/PTK6) mediates advanced cancer phenotypes via SH2-domain dependent activation of RhoA and aryl hydrocarbon receptor (AhR) signaling. Mol Cancer Res. Mol Cancer Res. 2021 Feb;19(2):329-345.

Dwyer AR, Truong TH, Kerkvliet CP, Paul KV, Kabos P, Sartorius CA, Lange CA. Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer. Br J Cancer. 2021 Jan;124(1):217-227.

Perez Kerkvliet C, Dwyer AR, Diep CH, Oakley RH, Liddle C, Cidlowski JA, Lange CA. Breast Cancer Res. Glucocorticoid receptors are required effectors of TGFβ1-induced p38 MAPK signaling to advanced cancer phenotypes in triple-negative breast cancer. 2020 May 1;22(1):39. PMCID: PMC7193415
 
Regan Anderson TM, Ma S, Perez Kerkvliet C, Peng Y, Helle TM, Krutilina RI, Raj GV, Cidlowski JA, Ostrander JH, Schwertfeger KL, Seagroves TN, Lange CA. Taxol Induces Brk-dependent Prosurvival Phenotypes in TNBC Cells through an AhR/GR/HIF-driven Signaling Axis. Mol Cancer Res. 2018 Nov;16(11):1761-1772. PMCID: PMC6214723