Biography

Digital Works: https://works.bepress.com/mary-alpaugh/

Education: 
BS (Biology & Philosophy), King’s College
PhD (Biochemical & Biophysical Sciences), University of Houston
Postdoctoral (Pathology), University of California, Los Angeles

Research Expertise: 
Cancer Biology | Tumor Progression | Metastasis | Intravasation

My research focuses predominantly on the molecular mechanisms of intravasation, the rate-limiting step of metastasis, and resistance/susceptibility of lymphovascular emboli to therapeutics.

Metastasis poses the single most difficult clinical challenge in the attempt to manage and treat cancer. In this effort, I have established patient-derived xenografts, signifcantly the first (and only) human transplantable inflammatory breast cancer xenograft, called MARY-X. Inflammatory breast cancer (IBC) is one of the most aggressive types of breast cancer; nearly 100% of all women with IBC have lymph node involvement and 25% have distant metastases upon diagnosis. The signature phenotype of IBC is florid lymphovascular invasion of cancer emboli. Whereas most human xenografts grow as a subcutaneous confluent cellular mass, MARY-X grows exclusively in the murine lymphatic and blood vessels, recapitulating the phenotype displayed in human IBC and in essence providing both a preclinical IBC model and a relevant model of metastasis. MARY-X, in vitro, is a primary cellular derivative from tumor explants. These tumor cells spontaneously form tight, compact aggregates of cells termed “MARY-X spheroids”. Comparable to human IBC emboli, a persistent, over-expression of an intact E-cadherin/α, β-catenin axis mediates the compaction of both in vitro and in vivo MARY-X spheroids and tumor emboli, respectively. The in vitro MARY-X spheroid has comparative 3-dimensional (3-D) architectural/pathophysiological features to the lymphovascular embolus. Therefore MARY-X provides a relevant 3D in vitro analysis platform for drug design and development of IBC and metastatic disease i.e. the lymphovascular embolus.

Member of:
American Association for Cancer Research

Recent Publications:

Kevin Daus*, Sorachat Tharamak*, Wanchai Pluempanupat, Peter A Galie, Maria A Theodoraki, Emmanuel A Theodorakis, Mary L Alpaugh. Fluorescent molecular rotors as versatile in situ sensors for protein quantitation, Sci Rep. 2023 Nov 22;13(1):20529. doi: 10.1038/s41598-023-46571-5.

Anna Rodina, Chao Xu, Chander S. Digwal, Suhasini Joshi, Yogita Patel, Anand R. Santhaseela, Sadik Bay, Swathi Merugu, Aftab Alam, Pengrong Yan, Chenghua Yang, Tanaya Roychowdhury, Palak Panchal, Liza Shrestha, Yanlong Kang, Sahil Sharma, Justina Almadovar, Adriana Corben, Mary L. Alpaugh, Shanu Modi, Monica L. Guzman, Teng Fei, Tony Taldone, Stephen D. Ginsberg, Hediye Erdjument-Bromage, Thomas A. Neubert, Katia Manova-Todorova, Meng-Fu Bryan Tsou, Jason C. Young, Tai Wang,* & Gabriela Chiosis*. Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation. Nature Communications (2023) 14:3742

Jagsi, G. Mason, B. A. Overmoyer, W. A. Woodward, S. Badve, R. J. Schneider, J. E. Lang, M. Alpaugh, K. P. Williams, D. Vaught, A. Smith, K. Smith, K. D. Miller on behalf of Susan G. Komen-IBCRF IBC Collaborative in partnership with the Milburn Foundation. Inflammatory breast cancer defined: proposed common diagnostic criteria to guide treatment and research. Breast Cancer Research and Treatment (2022) 192:235–243 doi.org/10.1007/s10549-021-06434-x.

Nagavarakishore Pillarsetty, Komal Jhaveri,Tony Taldone, Eloisi Caldas-Lopes,Blesida Punzalan, Suhasini Joshi, Alexander Bolaender, Mohammad M. Uddin, Anna Rodina, Pengrong Yan, Anson Ku, Thomas Ku, Smit K. Shah, Serge Lyashchenko, Eva Burnazi, Tai Wang, Nicolas Lecomte, Yelena Janjigian, Anas Younes, Connie W. Batlevi, Monica L. Guzman, Gail J. Roboz, Jacek Koziorowski, Pat Zanzonico, Mary L. Alpaugh, Adriana Corben, Shanu Modi, Larry Norton, Steven M. Larson, Jason S. Lewis, Gabriela Chiosis, John F. Gerecitano, and Mark P.S. Dunphy. Paradigms for Precision Medicine in Epichaperome Cancer Therapy. Cancer Cell 36, 1–15 Nov. 11, 2019 doi.org/10.1016/j.ccell.2019.09.007

Oraphin Chantarasriwong, Tanis J. Dorwart, Theodore Habarth Morales, Stephanie F. Maggio, Aspen L. Settle, Andrew T. Milcarek, Mary L. Alpaugh*, Maria A. Theodoraki*, and Emmanuel A. Theodorakis* Chiral resolution of a caged xanthone and evaluation across a broad spectrum of breast cancer subtypes. Bioorganic Chemistry 2019 Sep 21;93:103303. doi: 10.1016/j.bioorg.2019.103303

Mariano J. Alvarez, Pengrong Yan, Mary L. Alpaugh, Michaela Bowden, Ewa Sicinska, Chensheng W Zhou, Charles Karan, Ronald B. Realubit, Prabhjot S. Mundi, Adina Grunn, Dirk Jäger, John A. Chabot, Antonio T. Fojo, Paul E. Oberstein, Hanina Hibshoosh, Jeffrey W. Milsom, Matthew H. Kulke, Massimo Loda, Gabriela Chiosis, Diane L. Reidy-Lagunes, Andrea Califano. Unbiased Assessment of H-STS cells as high-fidelity models for gastro-enteropancreatic neuroendocrine tumor drug mechanism of action analysis. Nature Genetics 2019 Sep 23. doi: 10.1038/s41588-019-0509-5 

Oraphin Chantarasriwong,a,b,‡ Andrew T. Milcarek,c,‡ Theodore Habarth Morales,d Aspen L. Settle,d Celso O. Rezende Jr.,a Bashayer D. Althufairi,a Maria A. Theodoraki,d* Mary L. Alpaugh,c* and Emmanuel A. Theodorakis a* Synthesis, structure-activity relationship and in vitro pharmacodynamics of A-ring modified caged xanthones in a preclinical model of inflammatory breast cancer. European Journal of Medicinal Chemistry Apr 15;168:405-413 (2019). doi: 10.1016/j.ejmech.2019.02.047

Thorek, D.L.J., Watson P.A., Lee, S-G., Ku, A.T., Bournazos, S., Braun, K., Kim, K., Sjŏstrŏm, K., Doran, M.G., Lamminmăki, U., Santos, E., Veach, D., Turkekul, M., Casey, E., Lewis, J.S., Abou, D.S., van Voss, M.R.H., Scardino, P.T., Strand, S-E., Alpaugh, M.L., Scher, H.I., Lilja, H., Larson, S.M., Ulmert, D. Internalization of secreted antigen targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis. Science Translational Medicine: 30 Nov (2016). DOI: 10.1126/scitranslmed.aaf2335