Chromatin Dynamics in Stem Cells and Cancer Lab
Sylvester Comprehensive Cancer Center
Cancer Epigenetics Program
University of Miami-Miller School of Medicine
Our research aims to understand the epigenetic mechanisms mediated by the Polycomb-group complexes which underly cell fate decisions and cancer.
EPIGENETIC MECHANISMS IN BREAST CANCER
Breast cancer is one of the most commonly diagnosed maladies in women. In 2018, according to the American Cancer Society, more than 270,000 new cases of invasive breast cancer will be diagnosed in the US. Breast cancer is a heterogeneous disease originating from the basal and luminal cells of the mammary glands. Each of these subtypes has different risk factors for disease incidence, response to treatment, risk of progression, and preferential organ sites of metastases. Therefore, understanding the specific molecular and epigenetic mechanisms that control the oncogenic pathways deregulated in the different subtypes of breast cancer is crucial for the development of new therapeutic strategies.
PLURIPOTENCY AND DIFFERENTIATION
The potential to generate specific cell types capable of replacing damaged or aged human tissue is the vision of regenerative medicine. Human induced pluripotent stem cells (hiPSCs) hold promise to fulfill this vision, as they display the potential to differentiate into any specific cellular lineage. Despite tremendous advances, the molecular and epigenetic mechanisms that control hiPSCs pluripotency and cellular fate decisions remain poorly defined. We and others demonstrated previously that Polycomb-group proteins (PcG) orchestrate cell fate decisions and pluripotency in mouse embryonic stem cells (mESCs). However, the mechanisms whereby Polycomb proteins control pluripotency in human cells and drive stem cell differentiation into distinctive cell types remain largely unknown.
CHROMATIN ARCHITECTURE IN STEM CELLS AND CANCER
Chromatin structure is emerging as an important regulator of gene expression, cell fate determination and cancer progression. We are investigating the chromatin dynamics imposed by Polycomb complexes in stem cells and cancer models
POLYCOMB COMPLEXES ASSOCIATE WITH ENHANCERS AND PROMOTE ONCOGENIC TRANSCRIPTIONAL PROGRAMS IN CANCER THROUGH MULTIPLE MECHANISMS
Nature Communications, 2018
THE POLYCOMB GROUP PROTEIN CBX6 IS AN ESSENTIAL REGULATOR OF EMBRYONIC STEM CELL IDENTITY
Nature Communications, 2017
3D STRUCTURES OF INDIVIDUAL MAMMALIAN GENOMES STUDIED BY SINGLE-CELL HI-C.
LOSS OF ASXL2 LEADS TO MYELOID MALIGNANCIES IN MICE
Nature Communications, 2017
ANALYSIS OF ENDOGENOUS PROTEIN INTERACTIONS OF POLYCOMB GROUP OF PROTEINS IN MOUSE EMBRYONIC STEM CELLS
Methods Mol Biol. 2016
DNMT3A AND DNMT3B ASSOCIATE WITH ENHANCERS TO REGULATE HUMAN EPIDERMAL STEM CELL HOMEOSTASIS.
Cell Stem Cell, 2016
The Sylvester Comprehensive Cancer Center at University of Miami currently has an opening in our NIH-funded post-doctoral T32 Cancer Epigenetics Training Grant. A post-doctoral position is available for a research project studying the role of Polycomb complexes in cancer.
The laboratory of Dr. Lluis Moreyfocuses on studying the contribution of Polycomb group complexes in dictating cell fate determination of human stem cells and cancer. We recently showed that the Polycomb Repressive Complex 1 (PRC1) core subunit RING1B is amplified in multiple cancer types. Mechanistically, RING1B is recruited to active enhancers in breast cancer, leukemia and hepatocellular carcinoma, indicating a general and unexpected RING1B function in regulating oncogenic pathways in multiple cancer types (Chan et al. Nature Comm, 2018). Our previous work demonstrated that pluripotency and differentiation of embryonic stem cells (ESCs) is regulated by different Cbx-associated PRC1 complexes with unique functions (Morey et al. Cell Stem Cell, 2012; Morey et al. Cell Reports, 2013; Santanach et al. Nature Comm, 2017). Furthermore, we have identified that PCGF2 uniquely regulates PRC1 to specify mesoderm cell fate (cardiac and cartilage) in embryonic stem cells (Morey et al. Cell Stem Cell, 2015).
We are seeking an independent and highly creative postdoctoral fellow with experience in molecular biology, biochemistry, and/or structural biology. Familiarity with programming languages is important. Prior experience in epigenetics is preferred but not required. It is expected that the candidate will have the ability design experiments, collect and tabulate data, publish and present results, as well as to participate in the training of graduate and rotation students in a research laboratory setting. The project will include genome-wide studies of enhancer-promoter interactions, genome-editing, biochemistry and mouse models.
Ph.D. in molecular biology, cancer biology or related fields. Experience in a research laboratory setting. Evidence of scholarly ability (record of publication in peer reviewed journals, etc.). Ability to communicate in written and spoken English is absolutely required. Applications should include full curriculum vitae, publication list, information on years of experience in research and laboratory work.
Two reference letters, one of them from the Ph.D. advisor, are required.
Please note, Cancer Epigenetics T32 Training Grant Program applicants must meet the following criteria to be considered:
· Must be a US Citizens or Permanent Resident or a non-citizen national, or must have been lawfully admitted for permanent residence and possess an Alien Registration Receipt Card (1-151 or 1-551) or some other verification of legal admission as a permanent resident.
· Must be within 4 years of obtaining their Ph.D.
· M.D.s must be within 4 years of their residency or fellowship
· Candidates must be available for a Full-time, 12-month appointment and agree to undertake a minimum of two years of research, research training, or comparable experiences from the time of appointment.
· Must be accepted to a T32 Mentor’s lab
How to apply:Please submit CV, and contact information for 2 references combined into one PDF file by email to Dr. Lluis Morey email: