Molecular and Cellular Oncology
Molecular and Cellular Oncology Program
The Molecular and Cellular Oncology Program (MCO) organizes an outstanding group of researchers whose work provides insights into gene expression regulation and its deregulation in cancer, mechanisms underlying genomic integrity, the molecular structure of cancer-relevant proteins, and new signaling processes driving tumor growth.
Our researchers collaborate with other programs to translate their basic discoveries into better tools for cancer prevention, diagnosis, and treatment.
We develop these novel technologies and approaches:
- Advanced crystallographic, electron microscopy, and NMR studies of protein structure
- Cutting-edge metabolomics approaches to uncover weaknesses in cancer cells that can be exploited to therapeutic advantage
- Single-cell analyses to understand heterogeneity in normal tissues and tumors
- Synthetic lethal screens to identify pathways conferring resistance to targeted therapies
- New phospho-proteomics approaches to elucidate oncogenic protein kinase signaling pathways
- Identification of metabolic vulnerabilities in cancer stem cell populations
Scientific Goals
Research in the MCO program is directed toward elucidating fundamental biological processes in cancer biology and translating these basic discoveries into better tools for cancer prevention, diagnosis, and treatment through collaborative research with other CU Cancer Center programs and other cancer centers.
Research Themes
Maintenance of Genomic Integrity: Investigators work on genomic re-arrangements and retro-transposition; DNA replication, repair, and DNA damage checkpoints; and mutagenesis and response to ionizing irradiation.
Telomere Structure and Function: Across three campuses (Anschutz Medical Campus, CU Boulder and CSU Fort Collins), investigators lead research programs to understand telomere dynamics and regulation; their critical roles in cell division and genome integrity; and their dysregulation during spaceflight, aging and disease.
Gene Expression and Biomarkers: Investigators work on the specification of cell fates; nuclear acceptors of signaling and environmental pathways; fundamental mechanisms of transcriptional regulation; the interplay between transcription and RNA processing; mis-regulation of translation; cancer survival pathways; and identification of cancer biomarkers that result from altered gene expression including cell-free DNA biomarkers.
Structural Biology of Cancer Drivers: Investigators delineate the molecular structure of RNA & DNA-binding proteins involved in chromatin and oncogenes/tumor suppressors and signaling molecules using biophysical techniques, cryo-EM, NMR, and X-ray crystallography.
Pediatric Cancers: MCO members focus on high-risk pediatric sarcomas, blood cancers and brain tumors. Several MCO members are part of a highly collaborative pediatric brain tumor community that also spans DT and THI. A recent focus of this group has been to analyze the benefits and downsides of radiation therapy as part of brain tumor therapy.
Blood Cancers: MCO members study adult and pediatric pre-cancer malignancies and blood cancers including AML. Research projects span studies of molecular mechanisms to development of innovative clinical trials.
Programmatic Goals
- Promote career development for junior members and trainees
- Ensure engagement, access, and success for all members
- Stimulate inter- and intra- program collaborations
- Facilitate access to new technologies and resources
- Create forums for scientific exchange and discussion
- Discover basic cancer processes that can be collaboratively translated to the clinic
- Generate improved understanding and treatment of cancer types relevant to Colorado populations
MCO Program Activity Highlights
Molecular and Cellular Oncology (MCO) program welcomes Cecilia Caino, PhD, as our liaison to the offices of Community Outreach and Engagement (COE), Cancer Research Training and Education Coordination (CRTEC) and Engagement, Access and Success (EAS). Dr. Caino is an MCO member studying how mitochondrial biology impacts breast and prostate cancers. MCO co-leaders look forward to implementing the Cancer Center’s missions of research education, training and community engagement activities, including how to improve access to training and career development programs for all our trainees in collaboration with CRTEC and new initiatives to enhance success for all in our workforce in collaboration with EAS.
Discoveries by MCO members should benefit all cancer patients. Towards this end, MCO co-leaders continue to raise awareness regarding issues of access. At the 2021 MCO retreat as the keynote speaker and again as Cancer Center invited speaker, Anne-Kathrin Eisfeld, MD, from Ohio State University, presented on racial and socioeconomic disparities in survival of adult AML patients. At the 2022 retreat, MCO member Adam Green, MD, presented his work on pediatric cancer disparities. In 2023, our program retreat was held jointly with COE and CPC (Cancer Prevention and Control program), and featured MCO member Nikita Pozdeyev, MD, who described how genetic risk for cancer could be assessed across diverse populations through the Biobank at the Colorado Center For Personalized Medicine.
A brainstorming session at the 2021 MCO retreat produced many good ideas on how MCO can support researchers who want to incorporate race/ethnicity information into their work with bio-samples such as cell lines. MCO has compiled some resources to help Cancer Center members ensure that bio-samples in their experiments represent the population.
MCO co-leaders continue to infuse catchment-relevant issues into the scientific consciousness of MCO members, with the aim that such issues will guide future research in MCO. To this end, we invited leaders from the Community Outreach and Education office to attend our annual retreats and give talks. In 2021, Evelinn Borrayo, PhD, spoke about disparities in Colorado cancer patients. In 2022, Jan Lowery spoke about the COE mission and how it has integrated with cancer research projects and described resources available to researchers through the Biobank at the Colorado Center For Personalized Medicine. In 2023, our program retreat was held jointly with COE and CPC (Cancer Prevention and Control program), featuring a morning section devoted to catchment-relevant research projects. In 2024, Jeanette Waxmonsky, PhD, introduced the liaison program (see below).
Since 2023, MCO has joined forces with COE to award pilot grants with catchment-relevance. In 2023, pilots were awarded to Green for a project overcoming radiation-induced glioma in Colorado-based children; to a collaborative team led by Amaya for the role of inflammation in a VA population prone to myelodysplastic syndrome/T-cell leukemia; and to Su to study the effect of heavy metal runoff from mining on genome stability in Drosophila and human cell models. In 2024, an MCO-COE joint pilot grant was awarded to Sartorius to study the link between dietary fatty acids and breast cancer, the most commonly diagnosed cancer for Colorado women. Cell lines and patient specimens derived from Colorado patients will be used in this project.
We are excited to welcome MCO member Cecilia Caino, PhD, as our liaison to COE, CRTEC and EAS. Dr. Caino is an expert on how mitochondrial biology impacts breast and prostate cancers. MCO co-leaders look forward to implementing many ideas that we have discussed with her, including ways to disseminate our basic science findings to the public in collaboration with COE.
We hold annual retreats, rotating between campuses, which are typically held in November. Our 2023 retreat on the Anschutz campus was held jointly with CPC (Cancer Prevention and Control), including joint and separate events to promote cross-pollination of research approaches. Our 2024 retreat was held on the Boulder campus. Speakers include representatives from the office of COE to communicate the importance of serving our catchment and to present new tools to facilitate this work to our members. We also use this forum to have new mentored members featured as speakers, to facilitate new collaborations.
MCO also supports themed meetings that are developed from the ground up by our members. For example, a new recurring networking group meeting developed by early career MCO members Amaya and Caino was launched in 2023 with MCO support. It is called “Super Mito Group” and features Cancer Center and other regional faculty from the VA, Children’s Hospital and Jewish Health who focus on the role of mitochondria in health and disease, with a strong focus on how mitochondria are linked to cancer, including: 1) mitochondria as metabolic and signaling hubs in cancer, 2) underlying metabolic vulnerabilities in cancer, and 3) providing adaptation to cellular and therapy stresses and coordinating cell death in cancer. We also support the annual Colorado Genome Regulation meeting that brings together over 100 researchers from the state to present the latest in histone modifications, chromatin regulation, RNA-protein interactions in gene regulation and other topics. The keynote speaker in 2024 was Nobel Laureate Tom Cech.
To enhance our members’ awareness of NCI funding mechanisms, at our 2024 Program Retreat, we featured NCI Program officers describing some lesser-known funding initiatives and strategies. The materials from these program officers are available below:
Anu Sharman, Ph.D. - Overview of Funding Opportunities in Cancer Biology
John Giraldes, MS - NCI Drug Development Resources: Stepping Stones, NExT and Consultation Service
Colorado Biobank Portal
The portal supports queries across ~1,300 genome-wide association studies using ICD-derived PheCodes. The GWAS runs were performed on full TOPMed imputation and involve ~50 million sites along the genome in our currently-genotyped freeze of ~34,000 CCPM (Colorado Center for Personalized Medicine) participants.
Here is what you can do with the data:
Query by phenotype: Most phenotypes will autocomplete in the search bar. The mapping of phenotypes from ICD codes is available at https://phewascatalog.org/
Query by chromosome and position: The Portal shows SNP density in your region.
Query by gene or transcript: The portal shows all SNPs annotated to a gene as a table and a plot with variants in or near coding regions.
Do a phenome-wide association study (PheWAS) on the fly by querying a SNP of interest.
This portal is intended to provide preliminary analyses to support grant proposals and generate hypotheses. If you are interested in accessing the tool, register at https://ucdenverdata.formstack.com/forms/cbe_user_signup_ccpm.
Articles that explain the need to consider genetic ancestry and sex
Awareness is created by visibility talks about the need to have cell lines that represent human populations equally.
Misclassification of some cancer cell lines with regard to their genetic ancestry.
Ancestry matters: Building inclusivity into preclinical study design.
The need to use diverse cell lines in drug development.
Papers that address the genetic background of common cell line models
Carrot-Zhang et al., Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer. Cancer Cell 2020 May 11;37(5):639-654.e6. PMID: 32396860
Ghandi et al., Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature volume 569, pages503–508 (2019). PMID: 31068700 Supplementary Table 1
Dutil et al., An Interactive Resource to Probe Genetic Diversity and Estimated Ancestry in Cancer Cell Lines. Cancer Res 2019 Apr 1;79(7):1263-1273. PMID: 30894373
Kessler et al., Ancestral characterization of 1018 cancer cell lines highlights disparities and reveals gene expression and mutational differences. Cancer 2019 Jun 15;125(12):2076-2088. PMID: 30865299
Yuan et al., Integrated Analysis of Genetic Ancestry and Genomic Alterations across Cancers. Cancer Cell. 2018 Oct 8;34(4):549-560.e9. PMID: 30300578
Online resources with ancestry/sex information for biologics
UCCCReporter: Cell line ancestry for common cancer cell lines https://seandavi.github.io/UCCCReporter/reference/cell_line_ancestry.html
COSMIC (catalog of somatic mutations in cancer) https://cancer.sanger.ac.uk/cosmic
Cellosaurus, a knowledge resource on cell lines. https://web.expasy.org/cellosaurus/
Colorado Central Cancer Registry https://cdphe.colorado.gov/center-for-health-and-environmental-data/registries-and-vital-statistics/colorado-central-cancer
Funding
Please also see more current listings at https://medschool.cuanschutz.edu/colorado-cancer-center/research/funding-opportunities
Innovative Molecular Analysis Technologies - The IMAT program supports the early-stage development, maturation, and dissemination of novel technologies offering new or improved capabilities for basic, clinical, or epidemiological cancer research.
Informatics Technology for Cancer Research – The ITCR supports the development of critical tools and resources to improve the acquisition, analysis, visualization, and interpretation of data across the cancer research continuum.
Human Cancer Models Initiative
The goal of HCMI is to create up to 1,000 patient-derived next-generation cancer models (i.e., organoids, conditionally reprogrammed cells, neurospheres, or optimal growth condition models) as a community resource.
Patient-Derived Models Repository
The NCI is developing a national repository of Patient-Derived Models (PDMs) comprised of patient-derived xenografts (PDXs), in vitro patient-derived tumor cell cultures (PDCs) and cancer associated fibroblasts (CAFs) as well as patient-derived organoids (PDOs). These models will serve as a resource for public-private partnerships and for academic drug discovery efforts.
NCI Mouse Repository
The NCI Mouse Repository is a resource for murine cancer models, associated strains and mouse embryonic stem cells (mESCs) harboring inducible microRNA species. Managed by the Frederick National Laboratory, mouse strains are free, investigators only have to pay shipping costs.
Oncology Models Forum Webinar Series
This program is devoted to ensuring mammalian models used for translational research questions are appropriate robust representations for those purposes and the models provide reliable and informative data for patient benefit. Contact Christine.Nadeau@nih.gov if interested in attending an upcoming Webinars.
Molecular and Cellular Oncology Leadership
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Patricia Ernst, PhD
Program Co-Leader
Dr. Ernst is the Co-Leader for the Molecular and Cellular Oncology (MCO) Program. She is a Professor in the Department of Pediatrics, Heme/Onc/BMT section. Her research program focuses on childhood leukemia, normal hematopoiesis, and epigenetic factors regulating these processes. She has been continuously funded for over 17 years by grants from NIDDK, NHLBI, NIAID, OD, and NCI. Dr. Ernst served as Associate Director of the University of Colorado MSTP for seven years and is a former President of the International Society for Experimental Hematology. She serves on the editorial boards of Blood, Journal of Experimental Medicine, and Frontiers in Immunology. As program co-leader, Dr. Ernst serves as the site leader for the University of Colorado Anschutz Campus and a liaison for training programs at the University of Colorado Denver. Together with MCO co-leader Dr. Su she works to coordinate all aspects of MCO planning, development, execution, and evaluation.
Tin Tin Su, PhD
Program Co-Leader
Dr. Su is the Co-Leader for Molecular and Cellular Oncology (MCO) Program. She is a Professor in the Department of Molecular, Cellular and Developmental Biology at the University of Colorado, Boulder. She is an experienced investigator in the field of radiation biology of Drosophila and human cancer models. She is currently the PI of R35GM130374 and is one of two PIs for the NCI SBIR phase II contract 75N910196C00038. In addition to her role as program co-leader, Dr. Su serves as the Director of Graduate Student Affairs in her home department. She is the current President of the Drosophila Board and serves as the chair of NIH CSRS Study Section. She was appointed as program co-leader for MCO in 2018. As program co-leader, Dr. Su serves as the site leader for the University of Colorado Boulder Campus and a liaison for the Colorado State University and works closely with MCO co-leader Dr. Ernst to coordinate all aspects of MCO planning, development, execution, and evaluation.