Characterized by genetic instability and the capacity to adapt to selective pressure, cancer is one of the most multifaceted, heterogeneous, and intractable human diseases. Despite global efforts to control this life-threatening illness, the majority of cancers continue to resist even the most innovative drugs in the era of precision medicine. This fact underscores the enormity of the problem and highlights the urgent need to embrace alternative approaches to oncology research.

I am an American Cancer Society Postdoctoral Fellow and Trainee of the Ludwig Center at Harvard Medical School working in the laboratory of Dr. Peter Sorger. I study the systems immunology of an immunosuppressive brain cancer called glioblastoma (GBM). My decision to pursue a career in this area of research was motivated by the potential for immune-based therapies to create a survivorship for this currently incurable disease. The overall goal of my work is to synthesize an integrated and time-resolved comprehension of GBM’s influence over the cells, cytokines, and network-level architectures of the systemic immune system to ultimately determine if, and how, immunotherapy can be used to target this form of brain cancer.

I earned my doctorate of pharmacy (PharmD) from the University of Rhode Island then my PhD from the University of California, Los Angeles where I began researching malignant brain tumors in the laboratory of Drs. Pedro Lowenstein and Maria Castro. During this time, I contributed to a better understanding of GBM growth and invasion by showing that the tumor cells tend to migrate and proliferate within the potential space surrounding brain blood vessels and that this behavior is an angiogenesis-independent mechanism of tumor vascularization. As a graduate student I also uncovered a novel mechanism by which GBM blocks cancer immunosurveillance. Genetic knockdown of a β-galactoside-binding lectin called galectin-1 in GBM cells caused them to undergo apoptosis soon after their engraftment into the brain of syngeneic mice and rats. Additional experiments demonstrated the dependence of this effect on natural killer (NK) cells—cytotoxic lymphocytes of the innate immune system. These results were supported by clinical data showing that galectin-1 is frequently overexpressed by human GBM and is anti-correlated with patient survival.

Having observed the tumor’s ability to thwart the innate immune system, I was compelled to further evaluate GBM immunology from an integrated perspective. I knew that my ability to achieve this would depend on the collection of large experimental datasets and a firm grasp of computational data analysis. Thus, over the last three years in the systems biology lab of Dr. Peter Sorger, I have established a preclinical brain tumor initiative, collected systemic data from syngeneic mouse models of disease, and gained an expedient knowledge of computer programming. I now routinely use computer-automation in the analysis and visualization of network-level data. This approach has allowed me to better define the mechanisms that initiate and sustain GBM immune evasion, more accurately characterize its immunosuppressive hallmarks, and identify cell states perpetrating immunoregulatory behavior from outside of the brain.

My research has been enhanced by opportunity to network with leaders in the fields of cell signaling, metabolism, and clinical immuno-oncology thanks to the highly-cooperative research environment established by the Ludwig Center at Harvard Medical School. Through burgeoning partnerships, I plan to test the efficacy and modes of action of approved and emerging immunotherapies in the context of preclinical GBM. As I begin taking steps towards becoming the principle investigator of my own lab, I look forward to continuing my work in the area of brain tumor systems immunology. Despite its difficulties, I am regularly reminded of, and inspired by, the potential for my research to positively impact the lives of those touched by cancer. I would encourage those embarking on their own journey in oncology research to actively embrace a culture of interdisciplinary team science and to leverage the power of computation as a powerful means to scientific discovery.

Gregory J. Baker, PharmD, PhD