Precision Health member Dr. Sofia D. Merajver is Scientific Director of the Breast Cancer Program, Director of the Breast and Ovarian Cancer Risk Evaluation Program at the UM Rogel Cancer Center. Merajver is the GreaterGood Breast Cancer Research Professor, & Professor of Internal Medicine and Epidemiology at U-M.

Dr. Merajver’s research laboratory is devoted to understanding the molecular and metabolic regulators of very aggressive breast cancer types. The primary areas of focus are systems biology, mathematical oncology, biophysics, cell biology, genetics, and drug development. Dr. Merajver applies her extensive experience to help build and strengthen health programs at the University of Michigan, across the US, and collaborates with institutions in the Middle East, Africa, Latin America, and Germany. The goal of her global cancer work is to work closely with partners to create structures and health care delivery models to prevent cancer, diagnose it early and efficiently, and treat the disease and palliate symptoms in the most effective resource-appropriate manner.

Dr. Nate Merrill, PhD, is a Research Investigator in the Merajver Lab. His research interests involve the identification of biomarkers of drug efficacy in highly aggressive forms of cancer. Dr. Merrill’s academic training and research experiences span many disciplines, including chemistry, biochemistry, genetics, and molecular biology.

• Tell us a bit more about the details of your current research/projects

Our long-term goal is ultimately to pair the right patients with the right drugs; in each project we approach. While we have projects in two completely different disease contexts (lung cancer and breast cancer), the approach in both projects is really similar.

In triple-negative breast cancer, we have extensively tested therapies (>400 drugs) in 35 models of TNBC. In parallel, we have molecularly characterized these same samples (DNA sequencing, RNA sequencing, proteomics). Integrating the drug screening and molecular characterization, we can identify correlates of response that we hope to use to predict response in future samples.

In lung cancer, we are interested in cancers with a particular fusion of two proteins, EML4 and ALK. While we still have interest in screening cell lines and other preclinical models, these resources are extremely limited. For these EML4-ALK samples, we are collecting tissue from the operating room to test drugs and molecularly characterize, using material that is as close as possible to how it existed in a patient. The goal is to use this assay to predict better therapies for patients right now, and to seek new drugs and combinations to target resistance that develops during standard-of-care therapy.

• What is innovative/new/exciting about these projects?

We have worked to evolve with technology in all of our projects. All of our drug screening happens in 3D culture, and we are constantly evaluating newer models. We have fully embraced technologies like single cell sequencing and spatial profiling, and work to integrate these technologies into our work. The goal with our patient-derived material screening is to deliver results to clinicians and patients. This sort of cell-based testing would be the first cell-based assay to deliver results at the University.

• What is the anticipated outcome of this research?

We hope to bring our results to the clinic to become a tool for physicians to select therapies, delivering a ranked list of how we predict drugs will work for a particular patient. To get there, we are working to establish consistency with our assay and pairing this methodology with clinical trials to evaluate the positive predictive value of this platform. While mutations can recommend unranked lists of drugs, we are hoping that our complementary approach can evaluate multiple drugs within a class to deliver a ranked list.

• How does Precision Health support this research, and what about its’ ties to the precision health field? 

All of this work takes a village, and we have lots of collaborators who are part of Precision Health at UM. We are always looking for further opportunities for collaboration, especially in pairing our platform with clinical trials.

Our approach is complementary to many of the other efforts in precision medicine that utilize sequencing and big data to understand drug response. At the same time, our approach can be more agnostic, in that even if we don’t understand WHY, we ultimately want to pick the drug that is the best for the patient.

• What are your research interests, broadly?

Nate: My broad research interests involve the identification of biomarkers of drug efficacy in highly aggressive forms of cancer. The hope is that our work can be used to improve clinical trials to pair the right patients with the right drugs.

Sofia: My main work  goal is to make discoveries that can help patients right now. I think we finally have an alignment of all the technologies that make precision oncology possible.  Just as important, I aim to contribute to the careers of the next generation of translational molecular scientists of many disciplines, especially working in teams.  It is what I have always done.

• If you’d like, please provide links to recent/significant work
• https://merajver.lab.medicine.umich.edu/
• https://www.rogelcancercenter.org/judith-tam-alk-lung-cancer-research-initiative
• https://pubmed.ncbi.nlm.nih.gov/37377606/
• https://pubmed.ncbi.nlm.nih.gov/31655920/

We have a paper that will be submitted shortly that employs our platform in bladder cancer and tests material from 65 bladder tumors, so stay tuned for that in the near future.

• What do you like to do when you aren’t doing research?

Nate: As a relatively new father, I don’t get much down time. But when I can, I enjoy reading, getting outside, brewing beer, and soaking in Michigan sports.

Sofia: I enjoy writing, exercising, and being in nature. I love reading, movies, Argentinian folkloric music, classical music, and visual arts, and following Lionel Messi’s journey.