Cellular and Molecular Oncology

The overarching goal of the Cellular and Molecular Oncology (CMO) Research Program is to conduct basic,
cancer-relevant research to discover cellular and molecular mechanisms governing tumor initiation and cancer progression. We aim to translate our discoveries into diagnostic and prognostic biomarkers and targets for intervention in clinical and community settings. Guided by Community Outreach & Engagement (COE), we place an emphasis on cancers with high incidence, mortality, or differing outcomes in our catchment area. Conversely, clinical and community observations guide mechanistic CMO research. Thus, CMO acts as the hub of fundamental science, linking population-based research in the Cancer Control and Population Science (CCPS) Program and clinical-translation research in the Cancer Therapeutics (CT) Program.

We employ multidisciplinary approaches that combine sophisticated cell and tissue imaging platforms with computational modeling, and genetic and genomic analyses in cell and animal models with complementary biochemical and structural studies. These approaches are used to determine the molecular basis for disrupted genome regulation and cell signaling during carcinogenesis and the mechanisms by which exposures and other risk factors influence cancer development. We identify cancer-promoting mutations and genome-wide mutational signatures resulting from environmental exposures in CA cancers and combine the discoveries with studies focused on how these mutations perturb cellular functions, facilitating reverse translation. CMO members actively participate in Cancer Research Career Enhancement with CRTECC and also contribute to COE by participation in community outreach.

The CMO has three cross-cutting Scientific Aims:

1. Carcinogenic Mechanisms of Environmental Exposures: Discover the molecular and cellular mechanisms by which environmental carcinogens and behavioral risk factors relevant to our catchment area promote cancer.
2. Genome Regulation: Define the mechanisms and pathways by which genome stability, epigenetic alterations, and transcriptional regulation are disrupted in cancer cells.
3. Cellular Signaling and the Tumor Microenvironment: Determine how cell signaling pathways, cellular activities, and cell-cell interactions are altered during cancer initiation and progression and within the tumor microenvironment.

Aim 1. Carcinogenic Mechanisms of Environmental Exposures: Discover the molecular and cellular mechanisms by which environmental carcinogens and behavioral risk factors relevant to our catchment area promote cancer. The genetic, genomic, and biochemical processes affected by risk factors (e.g., tobacco use, viruses), toxic exposures, and environmental contaminants (UV radiation, arsenic, uranium) prevalent in NM are studied through the application of cell culture systems, model organisms, and human samples to define novel cellular and molecular mechanisms contributing to cancer and to identify potential diagnostic biomarkers.

Research Projects:

• Exposure to environmental metals, cancer etiology, and risk
• Environmental microplastics
• Arsenic & UV radiation (UVR) as co-carcinogens (also Aim 2)
• Transcription-coupled DNA repair (also Aim 2)
• Epigenetic alterations & genotoxic stress in lung carcinogenesis (also Aim 3)
• Genomic mechanisms underlying the disproportionate effects of cancers in populations (also Aim 2)
• MEK signaling as a therapeutic target in human papillomavirus (HPV)-induced pre-cancers (also Aims 2 and 3)

Aim 2. Genome Regulation: Define the mechanisms and pathways by which genome stability, epigenetic alterations, and transcriptional regulation are disrupted in cancer cells. Studies of the pathways that regulate genome integrity and function in normal and cancer cells are investigated using cell/tissue culture systems, animal models, and biochemical/biophysical approaches. Genome analyses define the spectrum of novel cancer-promoting mutations and mutational signatures reflective of environmental exposures and behaviors in catchment area-relevant cancers, particularly in American Indian and Hispanic communities. In turn, we define how these mutations disrupt normal molecular and cellular functions to promote carcinogenesis.

Research Projects:

• Advances in research on tobacco smoke exposure, electronic E-cigarettes, and lung cancer carcinogenesis
• Advances in DNA Damage Repair Research
• DNA replication & DNA damage repair
• Advances in studies using next-generation sequencing & genomic analyses to inform mechanisms responsible for differential cancer outcomes in our NM catchment area
• Advances in gene expression research
• Oncogene activation
• Arsenic & UV radiation (UVR) as co-carcinogens (also Aim 1)
• Transcription-coupled DNA repair (also Aim 1)
• Genomic mechanisms underlying the disproportionate effects of cancers in populations (also Aim 1)
• Epigenetic alterations & genotoxic stress in lung carcinogenesis (also Aims 1 and 3)
• MEK signaling as a therapeutic target in human papillomavirus (HPV)-induced pre-cancers (also Aims 1 and 3)
• Stem cells, circulating tumor cells & metastasis (also Aim 3)
• Auranofin & cisplatin as improved cancer therapy (also Aim 3)
• Iron chelation as prevention & treatment for colorectal cancer (also Aim 3)

Aim 3. Cellular Signaling and the Tumor Microenvironment: Determine how cell signaling pathways, cellular activities, and cell-cell interactions are altered during cancer initiation and progression and within the tumor microenvironment. We apply innovative cutting-edge imaging and genomics in normal and cancer cells to discover and dissect fundamental mechanisms whereby signaling pathways, cellular phenotypes, cell–cell interactions, and the tissue and tumor microenvironment are altered in and contribute to cancer.

Research Projects:

• Innovations in cell signaling research
• Spatiotemporal control of oncogenic signaling
• Advances in stem cell & microenvironment research
• Epigenetic alterations & genotoxic stress in lung carcinogenesis (also Aims 1 and 2)
• MEK signaling as a therapeutic target in human papillomavirus (HPV)-induced pre-cancers (also Aims 1 and 2)
• Humanized mice recapitulate complex tumor interactions with the microenvironment (also Aim 2)
• Stem cells, circulating tumor cells & metastasis (also Aim 2)
• Advances in Identifying Targetable Tumorigenic Pathways & Evaluating Therapeutic Approaches
• Ras-related Rac1 & Cdc42 GTPases targeted by R-ketorolac in cancers
• Auranofin & cisplatin as improved cancer therapy (also Aim 2)
• Iron chelation as prevention & treatment for colorectal cancer (also Aim 2)