From Bench to Desk: Transitioning from the Laboratory to Project Management

November 1, 2018, by Eva Tonsing-Carter, Ph.D.

My name is Eva Tonsing-Carter, and I recently became the Scientific Program Manager for the Human Cancer Models Initiative (HCMI) in the Office of Cancer Genomics (OCG) within the National Cancer Institute (NCI). HCMI is an international consortium that is developing next-generation human tumor-derived culture models that will better represent patients. The goal of HCMI is to find more clinically accurate and precise cancer treatments. Coming from the background of basic and translational cancer research in the laboratory, I wanted to further pursue research where findings at the bench lead to new therapies at the bedside. For this reason, managing clinical research projects at the OCG as the program manager for HCMI was an exciting subsequent step for me.

Throughout my adult life, I have always had a strong desire to understand the ‘how’ and the ‘why’. I completed my undergraduate studies in 2008 at Saint Mary’s College in Notre Dame, IN, where I earned a B.S. in Biology with a concentration in Molecular Cell Biology. It was during my senior year that I was able to conduct my first independent research project. I learned a lot during this period including time management skills, wet lab techniques, experimental design, and data interpretation. My project focused on characterizing erythogenic toxin gene expression in Streptococcus pyogenes, the bacteria that causes strep throat and scarlet fever. I examined patient samples to see if there was any correlation between erythogenic toxin gene expression and scarlet fever cases during the sample procurement time. As I learned my way around the lab and how to interpret experimental results, I gained invaluable experience that led me to pursue a Ph.D. in pharmacology.

In my quest to continue learning, I pursued my Ph.D. in Pharmacology at Indiana University-Purdue University, Indianapolis. The Indiana BioMedical Gateway Program allowed me to explore several specialty programs, and I chose to complete my Ph.D. training in the Department of Pharmacology and Toxicology. Throughout my coursework, I learned how and why drugs affect the body as well as how and why the body affects drugs. My research focused on the combination treatment of a standard of care chemotherapeutic drug, carboplatin, with a protein-protein interaction inhibitor, nutlin-3a, in triple-negative breast cancer models. I found that nutlin-3a led to potentiation of the carboplatin-mediated damage leading to increased cell death in vitro and decreased xenograft tumor growth and metastasis in an in vivo mouse model. I showed that this potentiation was in part dependent on p73, a family member of the well-known p53 protein family. My experience in this basic science laboratory sparked my interest in clinical research.

After completing my Ph.D. in 2014, I pursued further learning through postdoctoral training at The University of Chicago. The principal investigator of my postdoctoral laboratory is a medical oncologist who regularly sees and treats breast cancer patients. Many projects in the lab have resulted in the design of clinical trials and the research projects have also been influenced by clinical findings and questions. My lab had previously made an observation that in estrogen receptor positive (ER+) patients, high tumor expression of glucocorticoid receptor (GR) was associated with a relatively improved, relapse-free survival compared to patients with low GR tumor expression. My project focused on understanding how and why patients with ER+ breast cancer and high tumor GR expression may have an improved outcome compared to those patients with low tumor GR expression. Our laboratory found that GR modulation slows ER-mediated proliferation in vitro and associates with a decrease in ER-mediated, pro-proliferative gene expression. Utilizing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and ChIP followed by quantitative polymerase chain reaction, I found that the crosstalk between GR and ER receptors results in altered ER chromatin association in regulatory regions of genes that are important in cell proliferation. My hope is that the information gained through my research will be taken to the clinic to test GR modulators in ER+ breast cancer patients.

As I was considering the next step in my career, I wanted to expand my skills and knowledge in a larger context with broader impact. The HCMI project piqued my interested, and I joined the OCG this summer. Since starting my new position, I have transitioned from utilizing research tools to helping to create new research tools. My role with HCMI started by continuing to develop the case report forms for cancer types in which models are being developed. This role utilizes my research skills in learning more about a specific cancer type including clinical attributes, clinical biomarkers, and treatments. The clinical data is compiled, reviewed, and discussed with clinical collaborators to define which data elements are important to capture for all the researchers who may utilize the data generated through the HCMI program. The clinical data will be available alongside the sequencing data from the matched normal, primary tumor, and cancer model.

While the models are developed and expanded in the laboratory, the associated clinical data and sequencing data from the matched normal, primary tumor, and models are collected and submitted, quality checked, and harmonized for international accessibility. We are working to facilitate the development of the ‘HCMI Searchable Catalog’ where 1,000 models from a wide variety of cancer types including rare and pediatric, together with a subset of clinical data, will be searchable. Links to the models’ associated full clinical and sequencing data at the NCI Genomic Data Commons, as well as purchasing information from the third-party distributor, American Type Culture Collection, will be included in the catalog. Our goal is to launch the HCMI Searchable Catalog in early 2019. These next-generation in vitro models will allow for many downstream applications including high-throughput drug or CRISPR screens where other types of models have proven difficult (e.g. patient-derived xenografts). This process is a highly collaborative effort between all participants of the HCMI program including clinicians, scientists, data analysts, software developers, and project/program managers.

Additionally, NCI has a strong commitment to expanding racially and ethnically diverse research programs with the goal to decrease cancer health disparities. OCG has partnered with the Center to Reduce Cancer Health Disparities to fund several research supplement awards to allow for collection of tumors and generation of models from racial and ethnic minority cancer populations.

So far, my experience in OCG, albeit short, has already taught me so much not only about cancer and developing cancer models but also how to facilitate discussions across a broad range of contributors in large-scale program management. My background gives me a unique perspective as I was once someone who would have been utilizing the tools like the ones developed by the HCMI. Now, I am involved in helping to develop such tools and resources for the broader research community.

I am excited to see how HCMI continues to grow and expand. The next-generation in vitro models generated through the HCMI program have been created to provide more clinically relevant and representative cancer models than the traditional cancer cell lines. The HCMI models may provide better tools to understand how and why a cancer either responds or fails to respond to therapeutics. Expanding the types of cancer models, as well as increasing the number of models from racial and ethnic minorities, will further expand the breadth and scope of knowledge gained by the research community. My hope is that the information gained from utilizing the HCMI models will be taken from the bench back to the bedside and provide better treatment strategies for all patients.