Genetically engineered immune cell therapies have emerged as breakthroughs in the treatment of certain blood cancers. However, these advances have been limited to the minority of cancers that express a cell surface protein on all tumor cells; this protein is absent from essential normal tissues and can be recognized and targeted by therapeutic immune cells. Dr. Jan seeks to develop synthetic biology tools to engineer immune cells to recognize the heterogeneous tumor proteins present on many advanced cancers and then activate the body's tumor clearance mechanisms. His goal is to develop cell therapy candidates for direct translation to the care of people with advanced prostate cancer.

Dr. Jarjour is searching for novel methods to overcome resistance to immunotherapy. While immunotherapies have had a transformative impact for some patients suffering from specific cancers, some tumors are highly resistant to these treatments. These resistant tumors often lack the majority of immune cell types that could potentially attack the tumor. Dr. Jarjour is addressing this problem by developing antigen-independent methods to stimulate the innate proliferative capacity of tissue-resident CD8+ T cells, based on signaling molecules called cytokines. His generalizable approach could increase the efficacy of existing checkpoint blockade therapies on resistant tumors. His work has implications for many types of cancer, as well as vaccine development.

Every cell contains specialized compartments called organelles that perform distinct functions, and cells employ counting mechanisms to finely tune organelle population. Centrioles are one type of organelle required for proper cell division and mammalian development. Cells normally contain two or four centrioles, depending on cell cycle state, and centriole gains or losses result in cancer. One exception to this rule are the cells that line our airways, brain ventricles, and reproductive tracts. These cells contain hundreds of centrioles-yet how these specialized cells break the rules of conventional cell cycle-regulated counting mechanisms remains a mystery. Dr. Jewett's [Merck Fellow] work utilizes primary cell culture and in vivo models to understand the molecular framework that allows increased numbers of centrioles in certain cell types. This work will advance our understanding of how defects in centriole growth cause human diseases such as cancer. Dr. Jewett received her PhD from the University of Colorado School of Medicine and her BS from the University of Denver. 

Dr. Johnson [HHMI Fellow] studies the role that a particular type of cell-cell communication, known as quorum sensing, plays in the development of spatially structured bacterial communities called biofilms. Biofilm formation promotes disease in many clinically relevant bacterial species, and infections caused by them pose severe risks for patients receiving chemotherapy. Dr. Johnson is currently investigating how quorum sensing within biofilms establishes patterns of gene expression, and in turn, how these patterns drive biofilm development and dictate biofilm architectural features. By defining mechanisms underlying biofilm formation and biofilm architecture, Dr. Johnson hopes to contribute to the generation of new approaches for disrupting quorum-sensing-controlled bacterial community interactions as a means of combating bacterial pathogens. Dr. Johnson received her PhD from MIT and her BS from Yale University.

Dr. Kenney [Merck Fellow] studies how microbes make natural products, a major source of new chemotherapy drug candidates. Dr. Kenney is identifying the chemical reactions used by microbes in nature to synthesize compounds that have the potential to act as chemotherapeutic drugs. Once the biological synthesis of these compounds is understood, this information can be used to identify, investigate, and ultimately re-engineer new families of natural products that can be evaluated for their potential as novel drugs.

Cells are compartmentalized into membrane-bound and membrane-less organelles, providing spatial structure to the cell’s concentration of proteins and nucleic acids. Dr. Kilgore’s research aims to understand the environment inside different organelles and apply this knowledge to the development of targeted cancer therapies, as better targeting within the cell will improve drug efficacy, increase potency, and decrease side effects. Using both live cells and reductionist models, he will investigate how molecules distribute themselves within the cell as a function of their chemical properties. Learning and applying the chemical grammar of this spatial partitioning will enable the design and preparation of molecular probes and drugs that synergize with the chemistry of the cell as a mechanism of treating all cancers. Dr. Kilgore received his PhD from Massachusetts Institute of Technology and his BS from the University of California, Berkeley.

Dr. Kim [HHMI Fellow] is studying the molecular links between cancer cells undergoing metastasis and formation of the face during development (known as craniofacial development). Both craniofacial and cancer cells must enter a migratory state triggered by certain key transcription factors including TWIST1. However, the exact role of TWIST1 appears to vary across cell types, which might explain some of the differences between cells found in various cancers and in normal craniofacial development. Dr. Kim is using genomic tools to dissect how transcription factor cooperation may toggle TWIST1 function across cell types, with potential implications for all cancers.

Cells living in aggregates can perform more complex tasks than individual cells, but they also face key challenges as they have less access to space and nutrients. Tumors, like the healthy tissues they disrupt, must balance these physical forces and effectively distribute metabolites to continue to grow. Dr. Klumpe [Merck Fellow] will use yeast as a simplified model of cell aggregation to engineer diverse aggregates and observe their growth and maintenance over many generations. Understanding how certain properties of an aggregate affect its long-term stability can shed light on "design principles" that underlie the persistence of tumors, as well as what stabilizes other multicellular structures, such as healthy tissue and biomaterials. Dr. Klumpe received her PhD from the California Institute of Technology and her BS/BA from North Carolina State University.

Cancer cells rely on efficient uptake, conversion, and exchange of nutrients and vitamins to support their rapid growth and survival. The molecular transport channels that allow passage of nutrients between the different cellular compartments are critical for the survival of cancer cells and are thus promising as potential drug targets. However, drug discovery efforts are hampered by a lack of basic understanding of these channels' identities, functions, and regulation inside cancer cells. Dr. Kory's research aims to identify transporters central to cancer cell nutrient supply and detoxification pathways and determine their role in the emergence, survival, and aggressiveness of cancer. Her research is relevant to all cancers, but particularly pediatric, blood, and breast cancers.

Cancer initiation and progression stems from cell division errors that promote chromosome breakage and accumulation of mutations. Dr. Krishnamoorthy will use cutting-edge, cross-disciplinary approaches to provide insights into the fundamental question of how cell division shapes the cancer genome. Understanding the mechanisms of cancer genome complexity will help identify better diagnostics and treatments for cancers linked with high levels of genome alterations. Dr. Krishnamoorthy received her PhD from Vanderbilt University, Nashville and her MS from Middle Tennessee State University, Murfreesboro and her BS from PES Institute of Technology, Bangalore.