Dr. Adams [Marion Abbe Fellow] studies a specialized subset of immune cells that secrete potent antitumor cytokines called type I interferons (IFN-I). Within a tumor, these cells, called plasmacytoid dendritic cells (pDCs), are impaired, which contributes to an immunosuppressive state and cancer progression. Dr. Adams aims to uncover the molecular mechanisms that govern IFN-I production and pDC dysfunction in cancer. As dendritic cells are a promising cell therapy for cancer, understanding the regulation of pDC-IFN-I production can guide strategies to harness and integrate their anti-tumor function in new immunotherap

Dr. Andreeva focuses on structural and mechanistic aspects of inflammatory pathways underlying cancer and multiple other pathologies. Inflammation is an early response to various infections and damage initiated by the immune system. While it is essential for pathogen clearance and tissue repair, uncontrolled chronic inflammation promotes cancer development and all stages of tumorigenesis. Since inflammation is one of the hallmarks of cancer, understanding the processes leading to inflammation is critical for development of the next generation of cancer therapeutics. By using various structural, biochemical, and cell-based approaches, Dr. Andreeva aims to explain inflammatory pathways on a molecular level and provide a foundation for novel anti-inflammatory and anti-cancer treatments.

Dr. Ardy [Robert Black Fellow] is investigating the genetic determinants that govern the behavior of fibroblasts, a type of connective tissue cell that has been implicated in arthritis, heart disease, and cancer. Activated fibroblasts can exacerbate disease through various mechanisms, including remodeling tissue architecture and modulating the immune system. Dr. Ardy plans on using state-of-the-art genetic tools, including CRISPR inhibition and activation coupled with single-cell RNA sequencing technology, to uncover the proteins and pathways that regulate fibroblast behavior and thereby inform the development of new targeted cancer treatments. Dr. Ardy received his PhD from the Medical University of Vienna and his BS from the University of California, Los Angeles.

The connection between cardiovascular disease and cancer, the two leading causes of death in the United States, extends beyond cancer treatment’s impact on the cardiovascular system. These complex diseases share several important risk factors and aspects of disease progression. In the development of atherosclerosis, a build-up of fatty material in the arterial walls, vascular smooth muscle cells can change their roles and influence the progression of disease. Dr. Bell aims to determine if the same dynamic activity of smooth muscle cells occurs in the environment of a tumor, and whether these cells influence disease progression or response to therapies. Preclinical data suggests a significant role for these cells in the tumor environment for multiple solid tumor types, such as melanoma, breast cancer, and colon cancer. These findings could represent a new pharmacologic target for multiple cancers.

Evidence that aging is driven by defined, regulated processes (rather than simple “wear and tear”) has sparked hope that we might target these processes to fight age-related diseases. A particularly exciting example is the regulation of protein homeostasis, or the balance between protein synthesis, folding, and degradation. Protein homeostasis is deregulated in both cancer and normal aging, but the underlying mechanisms remain elusive. Dr. Boos will use the short-lived African turquoise killifish as a new model organism to study how different cells and tissues respond to protein misfolding, how they coordinate their responses, and how aging influences these pathways. This research will not only unravel fundamental mechanisms of aging, but also inform new strategies to fight multiple types of cancer. Dr. Boos received his PhD and his B.Ed. from the University of Kaiserslautern.

Dr. Bridges studies how bacterial cells form communities called biofilms that have particular three-dimensional architectures. He is investigating how the bacterial cell-cell communication process called quorum sensing drives the spatio-temporal gene expression patterns that govern biofilm formation. Biofilm bacteria are implicated as causal in various cancers and, furthermore, cancer patients receiving chemotherapy frequently suffer from infections caused by bacteria that rely fundamentally on biofilm formation for pathogenesis. By discovering the quorum-sensing program that bacteria execute to sculpt biofilm architectures, he hopes to contribute to the development of new strategies to interfere with formation of these bacterial communities.

Dr. Catipovic [HHMI Fellow] focuses on the mechanisms governing the resolution of errors that arise during RNA translation in mammals. Ribosomes translating the same message can collide if they are damaged or encounter blockages much like cars involved in a traffic accident. While cells can tolerate small numbers of these incidents, pervasive collisions overwhelm the cell and force it to make crucial decisions regarding long-term viability. Dr. Catipovic investigates the biochemical mechanisms governing this determination. He uses reconstituted translation systems, consisting of purified translation factors in vitro, as a tool to study the signaling pathways initiated by ribosomal collisions that effect the life-death decisions of severely stressed cells. Perturbation of these pathways can cause premature cell death or unregulated cellular proliferation, which is found in almost all cancers.

Proper cell division, including equal partitioning of DNA into two “daughter” cells, is critical for cell viability. However, many cancers continue to divide despite having atypical numbers of chromosomes and can even contain additional copies of the entire genome (polyploidy). Understanding how large increases in chromosome number affect cell division machinery has been limited by the methods used to generate polyploid cells. Serendipitously, stable polyploidy has arisen in multiple organisms, such as plants, fish, and amphibians. By utilizing the natural polyploidy found in Xenopus clawed frogs (ranging from two copies to twelve copies of the genome), Dr. Cavin-Meza [Merck Fellow] will explore the mechanisms that lead to increased but stable genome size. He will also analyze the proteome across Xenopus species to reveal how proteins have adapted to promote stable polyploidy over time, giving valuable insight into how stable polyploidy could arise in cancers. Dr. Cavin-Meza received his PhD from Northwestern University, Evanston and received his BS from the University of California, San Diego.

Dr. Chang is studying protamines—short, positively-charged proteins that condense DNA into chromatin and regulate gene expression in sperm nuclei. While eukaryotic cells use histones to package genomes in a way that allows access for transcription and replication, sperm cells must package their genomes more tightly. For this, many animals deploy protamines instead of histones. Despite sharing certain functions with highly conserved histones, protamines have independently arisen in evolution multiple times and are continuing to rapidly evolution. Using Drosophila fruit fly species as a model, Dr. Chang studies how sperm chromatin regulates gene expression and reproductive fitness. Additionally, although protamine expression is typically limited to testes, their misexpression has been observed in many cancers, indicating an opportunity for therapeutic intervention.

Dr. Chappleboim studies how cells communicate during a developmental process called somitogenesis, which drives the formation of repeated structures such as the spinal vertebrae. The signals that guide cell communication during this process can get misinterpreted by cancer cells, resulting in uncontrolled growth. These pathways are implicated in numerous cancer types but are notably associated with colorectal, ovarian, and breast cancer. Using cutting-edge techniques in human stem cells and 3D-models called organoids, along with the tools of computational biology, Dr. Chappleboim aims to deliberately perturb and examine these signaling pathways to gain a comprehensive understanding of how they function. Dr. Chappleboim received his PhD, MS, and BS from Hebrew University of Jerusalem, Jerusalem.