The Immunology, Microenvironment and Metastasis (IMM) Program explores the basic mechanisms of host-tumor interactions, immune responses and metastatic dissemination to create novel translational avenues for cancer diagnosis and therapy such as immunotherapy.
Wistar professor Rugang Zhang, Ph.D., has recently been appointed leader of the IMM Program, transitioning from his previous appointment as a co-leader of the Gene Expression & Regulation Program (GER). He succeeds Dmitry Gabrilovich, M.D., Ph.D.
Dr. Zhang leads a very productive lab studying the biology of ovarian cancer, the most lethal gynecological malignancy in the developed world, with the goal of developing novel therapeutic approaches to combat the disease with precision. In particular, the lab focuses on alterations in epigenetics, the set of heritable mechanisms that define how our genetic information is read and executed.
In the following Q&A, Dr. Zhang explains the impact and reflections his new appointment will have on the IMM Program and his own research.
Q: You have been part of the GER program ever since you joined Wistar in 2012. Does your new role and affiliation reflect a change in research direction for your lab?
A: In the current era, biomedical research moves at a breathtaking pace and the lines among different disciplines blur quicker than ever before. In the past few years, my research has expanded into understanding the interplay between ovarian tumor and its host microenvironment, in particular the immune microenvironment. While affiliated with the GER Program, I have been routinely attending the IMM programmatic meetings and have collaborated quite extensively with members of the Program prior to this change of affiliation. So in short, yes, the change is, to a large degree, a reflection of the natural evolution of my own research program.
Q: What are the immunology, microenvironment and metastasis aspects of ovarian cancer you are exploring?
A: We are actively studying the effects of an emerging class of therapies that work by targeting epigenetic pathways that are critical in ovarian cancer. Interestingly, in addition to acting on cancer cells, epigenetic drugs have a profound effect on the tumor microenvironment, including immune cells and other cells that facilitate cancer progression. We published a number of papers demonstrating that epigenetic drugs can work together with immunotherapy, such as immune checkpoint blockade, to suppress ovarian cancer. This approach may also be beneficial to prevent the development of resistance to individual therapies. In addition, we are very interested in exploring how epigenetic regulators control the dissemination of ovarian cancer, especially in the abdominal cavity. This process is comparable to metastasis in other types of solid tumors. In essence, we are studying immunology, microenvironment and metastasis from a gene expression and epigenetics point of view.
Q: What will your expertise and scientific accomplishments bring to the IMM Program?
A: As discussed above, my lab brings to the program a mechanistic perspective to study tumor microenvironment and metastasis. In addition, I believe our previous accomplishments in dissecting the interaction between ovarian cancer and the associated microenvironment will add new expertise to the Program and create opportunities for new synergy and collaboration.
Q: What is your vision for the Program moving forward in terms of research priorities and focus? How do you plan to implement it?
A: I envision the Program as a catalyzer of mechanism-guided translational research, complementing and synergizing with the other two Programs in our Cancer Center. I believe a stronger focus on mechanisms would enhance the vast therapeutic potential of the research conducted in the Program. We would like to foster disease-focused, collaborative research opportunities centered around the immune microenvironment and immunotherapy and leverage the unique strength in vaccine development in the IMM Program for cancer applications. Another short-term priority is taking advantage of the enormous amount of publicly available research databases to create a centralized database that could be used to generate clinical evidence-based hypothesis. The focuses of the IMM Program will be refined and sharpened through programmatic efforts and upcoming recruitment activities.
Q: What collaboration opportunities do you see?
A: In the present-day cancer research setting, collaboration is not an option, it’s a necessity, because development of effective therapies demands a more holistic view of cancer that looks at malignant cells in their ecosystem. Essentially, we are studying cancer as a disease organ whose uncontrolled growth depends on both cancer cells and their supporting microenvironment. For this reason, I see many many intra- and inter-programmatic collaboration opportunities. Specifically, my own research program will interface with pretty much everyone in the IMM Program. For example, we are actively collaborating with Dr. Mohamed Abdel-Mohsen on characterizing the role of sugar molecules in ovarian cancer dissemination and metastasis and with Dr. Andrew Hu on exploring the cellular stress response as a vulnerable target in defined subgroups of ovarian cancer. Of course, my research has and will always be rooted in the basic mechanisms of gene expression, which is the reason why I was in the GER Program for the past eight years. In addition, the Molecular & Cellular Oncogenesis Program (MCO) is critical in our understanding of cancer at the system biology level, which is also integral to my research program. In conclusion, I think my move to the IMM Program will strengthen both collaboration within the Cancer Center and across the Institute.