What makes one cancer more aggressive than another? What makes a tumor metastatic? These are the questions that I strive to answer through science. My field of research is translational cancer biology. Like many researchers that aim to contribute to the collection of knowledge about cancers and how to treat it, I hope to positively impact those who have been and will be affected by cancer.
My name is Martha B. Dua-Awereh and I am a postdoctoral fellow at the University of Arizona College of Medicine-Tucson in the department of Immunobiology. My laboratory is in the University of Arizona Cancer Center. My mentor, Dr. Alfred Bothwell, relocated to the University of Arizona from Yale University in June 2021. I joined the lab as his first University of Arizona postdoc in December 2021. Born and raised in Brooklyn, NY, I originally moved to Tucson in August 2019. During my graduate studies at the University of Cincinnati, where I obtained a Doctor of Philosophy in Systems Biology and Physiology, I studied metaplasia and regeneration in gastric tissue under the mentorship of Dr. Yana Zavros. I was fortunate to have the opportunity to relocate with Dr. Zavros when she moved to the University of Arizona and was granted permission by my graduate program to complete my dissertation research remotely, in Tucson. I graduated in December 2021. Although studying biological factors that drive metaplastic changes initially sparked my interest in cancer, it was the death of a loved one from metastatic lung cancer that ultimately solidified my determination to pursue cancer research.
The immunosuppressive environment of aggressive cancers is a significant barrier to effective and comprehensive treatment. Furthermore, there is no clear diagnostic evaluation to determine if a primary tumor will become metastatic. Elevated expression of the Wnt antagonist Dkk-1 (Dickkopf WNT signaling pathway inhibitor 1) transmembrane protein has been detected in the sera and tumor tissues of patients, in various cancer types, including those resistant to immunotherapy. Presence of Dkk-1 in tumor tissue is also associated with poor prognosis. Dkk-1 inhibits beta-catenin-dependent Wnt signaling and is involved in embryogenesis and development. Although previous research from our laboratory suggests that Dkk-1 may also have a role in tumor cell proliferation and regulates immune cell activity by inducing inflammation, the mechanism by which it does so is unclear. One research focus of our laboratory is trogocytosis. In trogocytosis (in Greek, “trogo” means gnawing or nibbling), one cell “gnaws off” part of the plasma membrane of another cell. This transfer allows a cell to acquire non-native surface proteins from other cells. My current hypothesis is that overexpression of Dkk-1 in tumors creates an immunosuppressive tumor microenvironment by facilitating the transfer of immune cell markers to tumor cells by trogocytosis and contributes to cancer metastasis. By elucidating the mechanism by which Dkk-1 promotes immunotherapy resistance and metastasis, I hope to gain a better understanding of how the tumor microenvironment impacts patient prognosis.
One of the models I used to study metaplasia, and now use to study metastasis, is the organoid model. Unlike cell lines, organoids are three-dimensional cellular structures that are formed from the stem cells of a particular organ. The stem cells recapitulate the differentiated cells and basic functional units of the organ or tissue they are isolated from. I culture organoids generated from human and mouse tumor tissues. From a tissue resection or a biopsy of a patient, we can generate organoids and perform in vitro experiments. For example, organoids can be co-cultured with different immune cells to determine which immune cells have the greatest impact on tumor proliferation and persistence. The strength of the organoid model is its physiological significance. We can observe in real-time how the cells and by extension, the organ will be affected. Organoids allow us to study how a tumor will respond to a drug or stressor. This gives researchers and clinicians a better prediction of how a patient will respond to different treatments and how additional factors such as immune cells or acquired proteins can affect the cancer cells. Cancers that I am currently researching are pancreatic, lung, and colorectal cancer. I hope to extend my research to breast and ovarian cancer, with a focus on health disparities in cancer treatment.
I am not only passionate about exploring the intricacies of cancer metastasis but also driven to help increase the number of underrepresented groups in STEMM (science, technology, engineering, mathematics, and medicine). We need more diverse representation within the patient populations we work with in research and more diversity among the scientists and clinicians that study cancer. As the first in my family to graduate from college and become a doctor, first in my family to be born in the United States (my family is from Ghana), being an African American woman, having a disability that is not visible and growing up with a socio-economically disadvantaged background, I have encountered several hurdles along my path to becoming a scientist. I understand why others who have had similar experiences can be deterred from pursuing STEMM fields. I use the knowledge I’ve gained from my experiences to help others to succeed and thrive in their own pursuits. In the past, I’ve encouraged my fellow students to major in mathematics, physics, and other STEMM fields of study. In graduate school as president of the SACNAS (Society for the Advancement of Chicanos/Hispanics and Native Americans in Science) Cincinnati chapter and regional director for Indiana, Michigan, and Ohio of the Student National Medical Association, I participated in several community outreach projects focused on science and health education. As a member of Zeta Phi Beta Sorority, Inc., I continue to raise awareness about health disparities in our local communities and encourage participation of underrepresented groups in the All of Us Research Program. Currently, I am a member of the Women in Physiology Committee of the American Physiological Society, continue to mentor students in my lab here at the University of Arizona and students at the University of Cincinnati, speak on panels about diversity in science, raise awareness about science and medicine through social media, and serve as a poster judge at conferences such as SACNAS and ABRCMS (Annual Biomedical Research Conference for Minoritized Scientists). My long-term career goals are to continue my development as a translational scientist, address health disparities through my research, and serve as an ambassador for diversity, equity, and inclusion in science and medicine.
You can connect with me on LinkedIn and Twitter (@MarthaDu). To learn more about our lab and our past and current research projects, visit our lab website at https://immunobiology.arizona.edu/research/bothwell-lab and our lab Twitter (@Bothwell_Lab).
Each month we'll feature a Postdoctoral Scholar and their research, sharing their experiences from the UA, life in Arizona and their research interests.