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. Informed by interactions with the UNMCCC Community Outreach & Engagement Office (COE), particular emphasis is given to cancers with high incidence, mortality, or unequal distributions in New Mexico, with discoveries translated into interventions in clinical and community settings.

In parallel, clinical and community-based observations guide mechanistic research by CMO members. This positions the CMO Program as the hub of basic mechanistic science, linking population-based research in the Cancer Control and Population Science (CCPS) Program and clinical/translational research in the Cancer Therapeutics (CT) Program. Furthermore, CMO members are actively engaged in cancer research training and education coordinated by the Cancer Research Training and Education Coordination Core (CRTECC).

The overall goals of CMO to discover fundamental mechanisms contributing to cancer etiology and progression are set forth in three Specific Aims:

1. Carcinogenic Mechanisms of Environmental Exposures: Discover mechanisms regulating cellular responses to environmental carcinogens and risk factors relevant to people in New Mexico.
2. Genome Regulation: Define mechanisms and pathways regulating genome stability, epigenetics, and transcriptional regulation that are disrupted in cancer cells.
3. Cellular Signaling and the Tumor Microenvironment: Investigate 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)