Dr. Zhang is developing a new form of cancer immunotherapy with improved safety and controllability. Redirecting the immune system to launch attacks on tumor cells has emerged as an extremely promising approach to fight cancer. One such strategy, named bispecific T cell engager antibody (BiTE) has shown remarkable efficacy against blood cancers, but it is also associated with severe toxicity. Using tools of synthetic organic chemistry, he aims to build a “chemical switch” that can be used to rapidly tune the activity of BiTE, thus allowing the circumvention of toxic side effects without diminishing therapeutic potential. The ultimate goal of this project is to develop a cancer immunotherapy that can be safely employed at doses effective for the treatment of solid tumors.

CAR T cell therapy, in which a patient’s own immune cells are reprogrammed to recognize and kill cancer, has revolutionized the treatment of blood cancers. Unfortunately, however, a significant portion of treated patients relapse, and CAR T cell therapy for aggressive solid tumors has been largely ineffective. A major roadblock preventing this therapy from curing more patients is the gradual loss of CAR T cells’ ability to kill tumor cells, which results in tumor progression or relapse. Dr. Weber aims to develop optimized killer CAR T cells that stay in the fight against cancer. His lab has developed a novel, high-throughput method of analysis that can be used to identify T cell characteristics, genes, and other biological features that enable CAR T cells to serially kill cancer cells. These insights will provide a roadmap for reprogramming T cells with enhanced tumor killing function, paving the way for more efficacious CAR T cell therapies and potentially other cancer immunotherapies for patients in need.

Cancer-associated pain can arise directly from tumor growth or as a side effect of chemotherapy drugs. First-line cancer treatments, such as cisplatin and paclitaxel, contribute to pain hypersensitivity by increasing the activity and expression of TRP ion channels—the receptors that detect painful stimuli in sensory neurons and trigger pain sensation. Research thus far has focused on how these receptors look and behave at a single-molecule level (one copy) or at a cellular/organismal level (many thousands of copies per neuron). However, TRP channels are also proposed to operate in nanoscale clusters (tens of copies) that amplify signaling within a sensory neuron. Dr. Cai’s research will use state-of-the-art microscopy techniques alongside biochemical and cell-based approaches to study how receptors are organized on the surface of sensory neurons. She aims to understand how inflammation and injury, including toxicity from chemotherapy drugs, contribute to acute and chronic pain. This work will provide fundamental insights into pain signaling that can inform the development of new pain management strategies. Dr. Cai received her PhD from The Rockefeller University, New York, and her BS from California Institute of Technology, Pasadena.

Many cancer treatments kill healthy cells along with cancer cells and tumors frequently adapt to treatment and build resistance. These challenges exist because the most important pathological cancer processes occur through complex interactions inside living cells, and the current models used to study cancer cannot fully mimic these complex living interactions. Dr. Zheng aims to combine large-scale genetic screening, advanced single-molecule imaging, and AI modeling to create detailed maps of how cancer-driving genes behave inside living human cells. These maps will show how networks of genes, as well as small DNA changes, alter the real-time behavior of powerful cancer drivers. This work will guide the development of treatments that cause less harm, stay effective longer, and act with far greater precision. Dr. Zheng received his PhD from Massachusetts Institute of Technology, Cambridge, and his BS from Peking University, Beijing.

CAR T cell therapy, which involves genetically engineering a patient’s own immune cells to seek and destroy cancer, has revolutionized the treatment of certain blood cancers. However, it frequently performs poorly against solid tumors because T cells become exhausted or cannot effectively detect the cancer cells. Dr. Banerjee aims to learn the fundamental molecular, genetic, and biophysical rules of internal signaling in T cells. By decoding these rules, he aims to design next-generation CAR T cells with enhanced sensitivity, persistence, and versatility. Taking an atypical approach, he will combine multiple cutting-edge technologies to dissect and engineer the “immunological synapse,” the connection that forms between a T-cell and a tumor cell, to ultimately tune the function of the T cells. This study aims to overcome current limitations in treating leukemias and extend the success of immunotherapy to solid tumors, specifically melanoma. Dr. Banerjee received his PhD from Johns Hopkins University, Baltimore, his MTech from the Indian Institute of Technology, Kanpur, and his BEng from Jadavpur University, Kolkata.

While much has been uncovered about the specific mutations that arise within a tumor, it is not fully understood how the DNA a person is born with (their inherited genetics) influences how those tumors grow. Dr. Mei’s research focuses on a specific, aggressive cancer gene called ERBB2, which is responsible for many breast, lung, and stomach cancers. Dr. Mei aims to discover if a patient’s inherited genetics makes them more likely to develop these specific tumor mutations or makes the cancer more dangerous. By understanding the interaction between a patient’s natural DNA and their tumor’s DNA, we can better predict cancer risks and find more effective, personalized treatments. Dr. Mei received his PhD from The Rockefeller University, New York, and his BS from Peking University, Beijing.

Cancer cells and certain immune cells inside tumors need a lot of energy to survive and function, creating a kind of “tug-of-war” for nutrients in the tumor’s environment. However, until recently, there has not been a good way to measure how these cells use nutrients for energy inside a living tumor. To tackle this challenge, Dr. Peace developed a new technology that can track which nutrients power a key energy pathway—the TCA cycle—in both cancer cells and immune cells, directly in vivo in tumors. By uncovering these details, his work aims to improve how we design cancer treatments, especially immunotherapies that help the immune system fight cancer more effectively. This work has the potential to be relevant for all cancers. Dr. Peace received his PhD and BA from Trinity College, Dublin.

Metastasis, the spread of cancer cells from primary tumors to healthy tissues, accounts for over 90% of cancer-related deaths. A protein called dynein is crucial for cell movement and research indicates that inhibiting dynein can reduce breast cancer cell spread. Typically, dynein moves toward the cell nucleus along microtubules from the plus-end (typically near the cell periphery) to the minus-end (usually near nucleus). However, during cell migration, dynein congregates at the microtubule’s plus-end by a process that is poorly understood. Dr. Mishra aims to establish the molecular mechanism underlying dynein’s localization at the plus-end of the microtubule. This understanding will help elucidate how dynein facilitates cell migration and metastasis, potentially leading to new cancer treatment strategies applicable to various cancer types. Dr. Mishra received his PhD from the Indian Institute of Science, Bengaluru, and his BS from Banaras Hindu University, Varanasi.

Our immune system uses many strategies to defend against viruses. Recent studies have uncovered a surprising bacterial antiviral strategy—instead of cutting DNA to destroy it, this system builds new DNA molecules to stop infections. Dr. He’s project will focus on understanding how this bacterial defense system works and explore whether this system can be repurposed to safely make DNA inside human cells. This could offer a new way to address a major challenge in the development of gene therapy and cancer immunotherapy more broadly: safely and efficiently delivering DNA into target cells without triggering harmful immune reactions. Dr. He received his PhD from the University of Wisconsin-Madison, Madison, and his BS from the University of Chinese Academy of Sciences, Beijing.

Asymmetric cell division is a mechanism by which adult stem cells generate one self-renewing stem cell and one differentiating daughter cell in order to maintain tissue homeostasis. A fundamental unsolved question is how two daughter cells adopt distinct cell fates (e.g., how one becomes a blood cell and one becomes a blood vessel cell) to prevent unchecked proliferation and tumorigenesis. Using fruit flies as a model system, Dr. Yu will investigate the selective inheritance of chromosomes for cell fate decision during asymmetric divisions of stem cells. This work will reveal a fundamental principle of how stem cells use chromatin-based mechanisms to determine cell fate and maintain homeostasis. Moreover, it will provide key insights into how cancer cells hijack these pathways to sustain their immortality and uncover novel vulnerabilities in cancer that could be targeted therapeutically. Dr. Yu received his PhD from Harvard University, Cambridge, and his BS from the University of Science and Technology of China, Hefei.