# Mechanisms of radiation-induced tumor cell death and survival in cervical cancer

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2020 · $226,318

## Abstract

PROJECT SUMMARY
The enclosed career development award is designed to prepare Stephanie Markovina, MD, PhD to transition
to independence as a physician scientist studying tumor cell death and survival in response to ionizing
radiation. Dr. Markovina graduated with honors in Biology from Washington University, then obtained her
medical and graduate degrees through the University of Wisconsin's Medical Scientist Training Program. After
finishing clinical residency in radiation oncology, she joined the faculty at Washington University, and has
become embedded in Dr. Gary Silverman's laboratory. She has demonstrated that SERPINB3, a member of
the serine protease inhibitor superfamily, mediates resistance to radiation in cervical cancer cells. She
proposes to investigate the mechanism of this cytoprotection and test the hypothesis that SERPINB3 prevents
lysosome-mediated cell death following IR as an innate and/or acquired defense mechanism.
Washington University School of Medicine is the ideal setting for Dr. Markovina to develop the remaining skills
necessary to transition to independence and to answer these critical questions. Expertise within the Radiation
Oncology Department and campus wide, as well as robust research resources facilitate a collaborative
environment that has produced some of the most impactful biomedical research. Dr. Silverman discovered the
SERPINB3 locus, and has since characterized various important functions of the intracellular serpins in human
physiology and disease, and their role in regulation of cell death mechanisms. Thus, this expertise along with
his track record of training young scientists make Dr. Silverman an ideal mentor for this proposal. Dr.
Markovina will take graduate level courses, present her work locally and at international meetings, and work
closely with Dr. Silverman and his group in order to develop key knowledge and technical skills in cell death
mechanisms, imaging techniques and animal tumor models.
Dr. Markovina has dedicated her early professional career to cancer research and navigated a unique path
through radiation oncology to become one of the few physician scientists in the field. She has found that
knock-out of SERPINB3 in cervix cancer cells results in a lower proliferation rate, and renders cells significantly
more sensitive to IR and to lysosome mediated necrosis in response to severe cell stress. Through the
proposed research she will 1) determine the mechanism of SERPINB3 cytoprotection against IR, 2) test the
hypothesis that SERPINB3 regulates IR-induced tumor cell death by targeting lysosomal cathepsins, and 3)
determine whether SERPINB3 functions as an oncoprotein promoting tumor growth, metastasis and survival in
the face of radiation treatment. Dr. Markovina's overall goal is to better understand mechanisms of cell death
and survival in cancer cells in response to ionizing radiation, which is critical to developing improved therapies.
Her motivation is not only her own patients und...

## Key facts

- **NIH application ID:** 9878095
- **Project number:** 5K08CA237822-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** STEPHANIE MARKOVINA
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $226,318
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878095

## Citation

> US National Institutes of Health, RePORTER application 9878095, Mechanisms of radiation-induced tumor cell death and survival in cervical cancer (5K08CA237822-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9878095. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*