Shivem Shah is one of a new generation of scientists who are developing therapies that will modulate the immune system to combat disease. They are called immunoengineers. A fourth-year biomedical engineering PhD Student, Shah first became interested in biomedical engineering because of the opportunity to create therapies for diseases with inadequate treatments. He is specifically drawn to immunoengineering for its potential to treat and possibly even cure diseases with poor prognosis, such as cancer.
Shah joined Ankur Singh’s research group, the Immunotherapy and Cell Engineering Laboratory (ICEL) at Cornell University after his bachelor’s degree in biomedical engineering from Boston University. The Singh lab creates 3D models, or organoids, of B cell development and cancer.
“An organoid can be informally defined as a mini organ-in-a-dish. An organoid should mimic an organ in terms of its function, architecture, and composition. We focus on modeling the B cell follicle of the lymph node,” says Shah.
B Cells and Lymph Nodes Explained
Shah compares the function of lymph nodes to military checkpoints. Intersecting blood and lymphatic vessels, lymph nodes are scattered throughout the body. While the circulatory system of blood vessels can be seen as the body’s premier highway, the lymphatic vessels run parallel to it and can be seen as the body’s garbage highway. This highway permits the transport of garbage, items foreign to the body, and garbage trucks, cells that carry these items. Upon reaching the lymph node, soldiers filter through the garbage and react appropriately to defend the body. The primary soldiers at lymph nodes are B and T cells.
These B and T cells recognize foreign bodies by the shape of antigens—specific molecules on the surfaces of invading bodies. Shah concentrates on B cells, which differentiate to produce antigen specific antibodies. He describes the antibodies as specific paintballs, since the binding of antibodies to antigens enables other immune cells to see and react to the antigen. For their specificity, manufactured antibodies have proven to be effective therapies for a wide range of diseases and are currently one of the fastest growing therapy types.
“B cells in the germinal center undergo a large number of mutations. We can look at these mutations as a double-edged sword.”
One of Shah’s research emphases is to create antigen specific antibodies, using the organoid system. In the body, B cells form specific antibodies by mutating their antibody genes in the germinal center, a process that is not fully understood and has been difficult to model outside the body. The Singh lab is one of the earliest labs to make a 3D model of the germinal center. Using this system, Shah and others produce antigen-specific antibodies in four to eight days, which is much faster and more effective than the current practice of using mice.
“We are now using the system to form antibodies against antigens that can be important markers of disease but often go overlooked by the immune system,” says Shah.
Using Organoids to Study B Cell Lymphoma
Shah’s research also aims to use the organoid platform to study B cell lymphoma. “B cells in the germinal center undergo a large number of mutations. We can look at these mutations as a double-edged sword. The mutations are necessary to make antibodies that are specific to a foreign body. An accumulation of mutations, however, can lead to cancer,” Shah explains.
B cell lymphoma, the result of these mutations, is being targeted by new specific therapies because of lymphoma’s heterogeneity and poor response to chemotherapy. The efficacy of these therapies varies among patients often due to differences in each patient’s cancer environment. Shah explains that using the organoid system to model the differences in the lymphoma environment could help predict if a patient would respond to certain treatments.
“In the future, I hope the organoid platform can inform patient-specific treatment plans and limit the need for extensive animal/human trials in identifying promising drug candidates,” Shah says. Shah attributes being able to balance both projects to a great lab environment, Ankur Singh’s mentorship, and his five talented undergraduate researchers—Elisabeth Abeles, Katherine Lee, Cassandra York, Nicole Edén Félix, and Cort Breuer.
Learning from the Community, as a Cancer Resource Volunteer
Outside of the lab, Shah volunteers with the Cancer Resource Center of the Finger Lakes. The center is a local organization that provides support to cancer patients through peer groups, financial advocacy, and wellness programs. Shah attends support group meetings every Tuesday.
“The center provides patients a path to wellness in their cancer recovery. I attend these support groups as a cancer researcher and as an aspiring future physician. It is a great opportunity for me not only to learn from their unique perspective as patients, but also to clarify any questions group members may have about their treatment or ongoing research,” Shah explains. He is also a West Campus graduate resident fellow in Flora Rose House and is thankful for the community there that has truly made Cornell his home.
Shah plans to pursue a career in medicine, working with cancer patients directly, while continuing to conduct research on personalized cancer therapies.