Cancer Cell Biology Research

Cancer Cell Metabolism

Research in cancer cell metabolism focuses on altered cellular metabolic pathways that support the cancer phenotype, which is characterized by unchecked cell proliferation, resistance to metabolic and oxidative stress, evasion of programmed cell death, reduced dependence on growth factor signals, insensitivity to growth inhibitory signals, and resistance to therapeutic interventions.

Key research areas include:

• Oncogenic reprogramming of cellular metabolism (e.g., the Warburg Effect, glutamine addiction, upregulated/deregulated fatty acid metabolism)
• The links between protein translation, ribosome biogenesis, and metabolism
• Tumor metabolite profiling and characterization
• Regulation and mechanisms of nutrient, metabolic intermediate, as well as ion transport and processing in cancer cells
• The molecular mechanisms that lead to cancer cachexia

Emerging areas in cancer metabolism include biological functions of metabolic intermediates, the molecular link between body homeostasis and cancer cell biology, mechanisms underlying the intersection between obesity and cancer, the metabolic plasticity of cancer cells, and the mechanisms through which diet and fasting affect cancer initiation and maintenance.

Cancer Cell Stress Responses

Research in cancer cell stress responses focuses on the cell’s reaction to intrinsic and environmental stressors that determine whether a cell will die or adapt to survive. Examples of the types of stress included in this research area are oxidative stress, oncogenic stress, accumulation of unfolded or misfolded proteins, hypoxia, metal ions, chemotherapy, and inflammation.

Key research areas include:

• Mechanisms of cell death (e.g., apoptosis, necrosis/necroptosis, autophagy, anoikis, ferroptosis, and other forms of programmed/non-programmed cell death)
• Recycling of cellular components in response to stress (e.g., autophagy, mitophagy, lipophagy)
• Endoplasmic reticulum (ER) stress and the unfolded protein response
• Exosome release as a mediator of cellular stress response and intercellular communications
• Altered processing of growth factors and their associated receptors
• Mechanisms of cellular control of toxic byproducts from biological processes (e.g., redox control)

Emerging areas relevant to this research include novel exosomes and cell-cell micro-channels exploited by cancer cells, mechanisms of metal ions homeostasis, such as iron and copper, and their associated cellular targets and functions, and understanding the global effects of metal ions accumulation.

Organelle Biology

Research in organelle biology investigates the mechanisms and role of dysregulated organelle biology in driving or supporting the cancer phenotype.

Key research areas include:

• Dysregulation of organelle biogenesis and function (e.g., mitochondria, endoplasmic reticulum, Golgi, lysosomes, lipid droplets, peroxisomes, endosomes, and cilia)
• Processing and trafficking of intracellular membranes and proteins
• Endocytosis and endosome sorting and recycling
• Interactions between nuclear-encoded oncogenic proteins and mitochondrial function
• Role of cell organelles in cancer-associated phenotypes

Emerging areas relevant to this research include regulation of mitochondrial growth and division, energy-independent functions of mitochondria.

Cancer Cell Cycle Control

Dr. Sita Kugel Investigates the Biology of Pancreatic Cancer and Cholangiocarcinoma

Cell cycle dysregulation is a hallmark of cancer, and cell cycle components have been aggressively targeted in cancer therapeutic strategies. Research in this area focuses on altered cell cycle regulation and its contribution to oncogenic transformation and tumor maintenance.

Key research areas include:

• Characterization of factors that regulate cell cycle, mitosis, cytokinesis, centrosome duplication, and DNA replication in cancer cells 
• Alternative, kinase-independent functions of cell cycle regulators
• Mechanisms that alter protein stability and function of cell cycle components in cancer cells
• Understanding the biological effects of cell cycle inhibitors in tumors, either alone or in combination with other therapies

Emerging areas relevant to this research include the elucidation of nutrient-sensing cell cycle checkpoints,  understanding mechanisms that allow for the bypass of cell cycle checkpoints, and exploration of combination therapies with CDK inhibitors for certain cancers.

Post-transcriptional Regulations Influencing Cancer

Research in this area investigates the wide-ranging mechanisms and functional effects of post-transcriptional regulations and their cross-talk  that affect  the cancer phenotype.

Key research areas include:

• Altered mechanisms and regulations of RNA stability, splicing, modifications, transport, and mRNA translation
• Regulation and mechanisms of alternative splicing in cancer
• The role of non-coding RNAs and RNA binding proteins in the regulation of splicing, modifications, transport, translation, and mRNA stability
• Translation factors that act as oncogenes or tumor suppressors
• Changes in protein maturation and stability, including diverse post-translation modifications (e.g., phosphorylation, acetylation, methylation, hydroxylation, ubiquitylation, sumoylation, neddylation, and glycosylation), as well as modifications of signaling effectors (e.g., promotors and drivers of tumorigenesis or cancer progression)

Emerging areas relevant to this research include the study of chemical modifications to RNAs and protein molecules, including writers, erasers, and readers of such modifications, that affect their stability, trafficking, RNA splicing and translation, and protein function, the development of novel technologies for efficient profiling of these modifications, and the interplay between different modifications and their alterations in cancer.

Basic Mechanisms of Cell Transformation

Research in this area includes mechanisms and effectors that govern the transition from normal cell to pre-cancer, early lesion, and cancer cell, as well as the identification of early biological events in transformation. Studies cover the role of tumor-initiating cells, field cancerization, cell state changes, and cellular signaling pathways governing cell fate determination and tumor formation. Research also examines the functions and regulations of oncogenes and tumor suppressor genes/proteins.  

Key research areas include:

• Functional and molecular characterization of oncogenes and tumor suppressors and their affected pathways, as well as oncogene dependencies in cancer
• Oncogenic signal transduction and their rewiring during tumor initiation, growth, and response or resistance to treatment
• The biology of tumor-initiating cells and cancer stem cells
• Cancer cell states and plasticity influenced by various effectors including injury, inflammation, cell/tissue of origin, etc.
• Role of developmental and early cell/lineage commitment programs in preneoplasia and cancer
• Senescence as an oncogenic or tumor suppressive mechanism, the relationship between quiescence and senescence states, and the relationship between senescence, aging, and cancer

Emerging areas relevant to this research include understanding lineage affiliation of stem and progenitor cells and its role in oncogenesis, characterizing the actual cell targets for oncogenic transformation, and deciphering the functional effects of multiple mutations in normal cells and their role in transformation.

Biospecimen Resources to Support Cancer Biology Research

Research in this area includes the development of projects that encompass the collection, storage, processing, and dissemination of human biological specimens—including nucleic acids and tissue arrays—and associated models and data for studies of human cancer biology, particularly early events in cancer formation and pre-neoplasia.