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.

Cancer is fundamentally a disease of lost tissue integrity, in which cells fail to properly coordinate and regulate one another, leading to abnormal cell growth and invasion within tissues. Dr. Hung aims to uncover basic principles of how cells combine chemical and mechanical signals to maintain tissue integrity. Using flatworms that are capable of tissue regeneration as a model, he will employ live whole-worm imaging of tissue regeneration to study mechanical and chemical signaling at the cellular level. This project will provide key insights about the logic of multicellular signaling circuits for maintaining normal tissue integrity and clues about how these signaling circuits can be dysregulated in cancer. Dr. Hung received his PhD from Stanford University, Stanford, and his BS from the University of Washington, Seattle.

Many different kinds of mutations affect cancer genomes, but the most recurrent are copy number alterations, resulting in a cancer cell with more or fewer copies of a gene than a normal genome. Dr. Baslan is focused on developing novel therapies that target this class of mutations with an emphasis on deletion events. More specifically, using a combination of advanced algorithms and chemical biology tools, Dr. Baslan is investigating specific vulnerabilities that are associated with deletion events and developing strategies to target these sensitivities in pancreatic cancers. Ultimately, Dr. Baslan aims to explore the generalizability of these therapeutic strategies across cancers, as the majority of cancer genomes contain recurrent deletions.

Kinase pathways control how cells grow, divide, and survive. When they malfunction, they drive many forms of cancer. Abnormal kinase signaling also contributes to resistance against current therapies. Rather than blocking these pathways as traditional treatments do, Dr. Zhou’s research explores ways to change the outcome of aberrant kinase signaling. By redirecting these pathways toward anti-tumor responses, this approach has the potential to provide more durable treatments for cancers that evade existing therapies.

Many cancers evade immune attack by creating a local environment that suppresses immune cells, thereby preventing sustained anti-tumor responses. Dr. Carnevale’s research focuses on dendritic cells, which play a central role in activating cancer-fighting T cells. She seeks to understand how these cells can be reprogrammed to function within tumors despite suppressive signals. In addition, she plans to develop new approaches to engineer dendritic cells so they can physically and functionally coordinate multiple types of T cells within tumors, strengthening local immune responses. Ultimately, this research aims to uncover new strategies to harness dendritic cells to overcome immune resistance in cancer.

While much progress has been made in understanding cancer immune responses, natural killer T (NKT) cells remain understudied. These immune cells act as a bridge between innate and adaptive immunity, rapidly responding to targets through their distinctive receptor. This receptor recognizes lipid molecules, but we currently do not know what tumor lipids can activate NKTs or how NKTs help the immune system attack tumors. Dr. Ferris will investigate how NKTs are involved in the cancer immune response, with the goal of defining how NKT cells are activated by tumor lipids and what those lipids are. This research not only seeks to expand our understanding of fundamental immunological processes but also holds potential to develop immunotherapies to target multiple cancer types using NKT cells.

Many cancers develop when crucial “cellular machinery” malfunctions. One component of this machinery is the ring ATPase, which harnesses the energy from ATP to perform essential tasks such as maintaining protein homeostasis and ensuring genome stability—processes vital for preventing uncontrolled cell growth. Understanding precisely how these complex human ring ATPases operate and coordinate their actions remains a significant challenge. Dr. Xu’s [HHMI Fellow] research focuses on a mechanically similar, yet structurally simpler, ring ATPase found in the φ29 bacteriophage. By filming high-resolution “movies” of this viral ring ATPase in action using advanced single-molecule techniques, Dr. Xu aims to uncover the fundamental principles of its mechanochemical cycle. This will reveal, step-by-step, how it converts chemical energy into the precise mechanical forces and coordinated movements required to stabilize DNA. This work is relevant to a range of cancers where cellular ring ATPases are dysregulated, and the insights gained could pave the way for novel therapeutic strategies targeting these essential molecular machines. Dr. Xu received his PhD from Vrije Universiteit, Amsterdam, his MS from the University of Chinese Academy of Sciences, Beijing, and his BS from Northeast Agriculture University, Harbin.

Genetic disturbances can disrupt normal cellular programs, promote unrestricted proliferation (i.e., tumor growth), and expose vulnerabilities that can be targeted therapeutically. However, how cells dynamically respond to such changes over time remains incompletely understood. Dr. Torre [Kenneth G. and Elaine A. Langone Fellow] will use cutting-edge genetic tools, such as CRISPR and single-cell RNA sequencing, to study the precise sequence of molecular events triggered upon silencing of key regulators of cell identity and proliferation in human cells. By combining single-cell data with advanced statistical modeling, this work will reveal how gene perturbations dynamically alter cellular networks and drive survival or cell death, thus helping inform the development of novel cancer treatments. Dr. Torre received his PhD from the Icahn School of Medicine at Mount Sinai, New York, and his BS from the University of Trieste, Trieste.