Kristin Ann Altwegg, a fourth-year student in the Cancer Biology discipline of the Integrated Biomedical Sciences Ph.D. program at UT Health San Antonio, received 3rd place for the predoctoral poster presentation category at the Virtual Mays Cancer Center annual symposium. Altwegg is an affiliate member of the Mays Cancer Center, home to UT Health San Antonio MD Anderson. She is also a CPRIT Predoctoral Fellow. Her mentor is Ratna K. Vadlamudi, Ph.D.

The Pipette Gazette had a few questions for Kristin. 

What did you present at the symposium?

I presented part of my dissertation research at the 2021 Virtual Mays Cancer Center Retreat. Mutations in Estrogen Receptor-alpha (ERα/ESR1) genes (30-40% frequency) play an important role in acquired endocrine therapy resistance and metastases in breast cancer (BC). Mutant ERα (mtERα) proteins constitutively interact with coregulators and promote breast tumor growth. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), an oncogenic coregulator of both wtERα and mtERα, plays a critical role in ERα signaling and its dysregulated expression is a prognostic indicator for poorer BC survival. The objective of this project is to develop and test the utility of first-in-class Small Molecule Inhibitor of PELP1 (SMIP34) for treating BC driven by mtERα. My studies confirmed that BC model cells expressing mtERα have increased cell proliferation, whilst PELP1 knock-down significantly reduced their proliferation. I found that treatment with SMIP34 significantly reduced proliferation in the four mtERα BC models and resulted in downregulation of expression of mtERα target genes. Further, SMIP34 treatment significantly reduced the invasiveness and colony formation in these four models.  Mechanistic studies confirmed that SMIP34 contributed to PELP1 degradation. Most importantly, SMIP34 treatment significantly decreased proliferation of mtERαBC cell lines and tumors both ex vivo and in vivo using xenograft derived explants, patient derived explants, and xenograft derived tumors as measured by Ki67 staining.

Why were you excited to present this research?

I was so excited to present this portion of my dissertation research because my results suggest that PELP1 associates with mtERα and targeting the PELP1 axis with SMIP34 has potential therapeutic utility in treating therapy-resistant BC.

How did you feel when you found out you won this award?

I was so surprised I didn’t hear the announcement of any of the other awardees!  I would like to take this brief moment to congratulate both the predoctoral and postdoctoral award winners, and thank all of the participants, judges, and contributors at the 2021 Virtual Mays Cancer Center Retreat.

What are the next plans for your project?

I have submitted a first author review article covering the role of coregulators in estrogen hormone signaling and therapy resistance which is under revision at this time. On the bench I am working to complete the figures needed for a first author publication on this branch of my dissertation proposal.  Future plans are to design and then finish the next phase of my dissertation focusing on characterizing the utility of SMIP34 in treating triple negative breast cancer.

Anything else you want to add.

I was selected by American Association for Cancer Research to participate in AACR-Early Career Hill Day.  This is an important opportunity for me to be able to speak with our senators and representatives in Washington, D.C. on the importance of sustained and continued funding for cancer research initiatives under the NIH and NCI.  I am honored to be able to speak with our legislators about the importance of these funding initiatives to me personally, to UT Health San Antonio, and to cancer patients both current and future. As someone who’s research has been funded by CPRIT and the NIH, I believe it is my duty to share the impact of this financial support during my early career and the possible translational research advances I am able to contribute to as a result.