Ronald Parchem

Ronal J. Parchem

 

E-mail: ronald.parchem@bcm.edu

Assistant Professor, Baylor College of Medicine

B.S., University of Illinois, Urbana-Champaign, 1999
Ph.D., University of California, Berkeley, 2008
Postdoc, University of California, San Francisco, 2009-15


 Neural development, neural crest development, stem cells and cancer biology

Embryonic and neural crest stem cells

Embryonic stem cells derived from blastocysts or generated via somatic cell reprogramming possess pluripotent potential and have received considerable attention due to their remarkable ability to generate all cell types of the body. Interestingly, another type of highly potent and migratory pluripotent stem cell is found during early vertebrate development. Known as neural crest cells, this cell lineage generates an incredible diversity of cell types such as the peripheral nervous system, bones and cartilage of the face, smooth muscle, and melanocytes. Despite their unique migratory and highly potent properties, relatively few studies have focused on their possible uses in regenerative medicine and as a model for metastasis. Additionally, many diseases and birth defects are associated with neural crest cells. Therefore, our goal is to understand the mechanisms that neural crest cells use to make cell fate decisions and acquire pluripotency from a previously restricted ectodermal lineage. Specifically, we have identified a microRNA cluster that plays a major role in neural crest specification and differentiation. Using genetic, molecular, and genomic approaches we aim to identify important mechanisms underlying neural crest development and apply these insights towards therapeutic intervention and disease study. These include the generation of neural crest cells in vitro for disease modeling and directed differentiation of neural crest cells into therapeutic cell types to treat patients. We use several model systems including the mouse, chick, human embryonic stem cells and tumor cells to address important questions.

Placental development

Placental mammals possess the ability for prolonged intrauterine development via the evolution of a special organ called the placenta. The placenta has the remarkable ability to invade the uterus of the mother without inducing an immune response and then becomes a major source of hormone secretion and nutrient delivery throughout gestation. Development of the placenta is poorly understood despite being a major cause of pregnancy related diseases and preterm birth. Furthermore, the invasion, immune tolerance, and vascular remodeling that occur during placental development reflect several aspects of cancer progression and tumorigenesis. We are currently trying to understand the developmental basis for placental diseases using a mouse model alongside clinical collaborations to study human tissue and fluid samples.

Cancer stem cells and metastasis

Tumor cells with stem-like properties have been shown to play pivotal roles in multiple types of cancer. Indeed, cancer stem cells have been implicated in some of the most lethal characteristics of cancer, including metastatic spread, tumor re-growth following treatment, and resistance to chemotherapy. Cancer stem cells display a phenotype that is strikingly similar to embryonic stem cells, strongly suggesting that cancer develops the ability to replicate uncontrollably, spread around the body, and renew itself following treatment, through a process of reverse embryonic differentiation, or “de-differentiation.” We recently studied the most highly expressed miRNA clusters in embryonic stem cells and found that they regulate hundreds of genes involved in cell biological processes such as cell death, proliferation, signaling, and differentiation. Accordingly, we hypothesize that embryonic miRNAs regulate the stem-like properties of cancer stem cells. Specifically, several reports have indicated that embryonic miRNAs are up-regulated in cancer stem cells analogous to their high levels of expression in embryonic stem cells. Future work in my lab will focus on understanding how embryonic miRNAs drive de-differentiation and metastasis across various types of cancers. Specifically, we have collaborations with clinicians to obtain patient tumor samples to derive primary cell lines and characterize miRNA expression in solid tumors. Additionally, using mouse models of cancer and xenograft studies we aim to mechanistically understand how embryonic miRNAs endow cancer stem cells with their unique properties. These studies have the potential to uncover novel targets for therapeutic approaches to cancer and identify predictive miRNA biomarkers for metastatic disease.


Selected Publications

Parchem RJ, Perry MW, Patel NH (2007) Patterns on the insect wing. Current Opinion in Genetics Development 17:300-308.

Parchem RJ, Ye J, Judson RL, LaRussa MF, Krishnakumar R, Blelloch A, Oldham MC, Blelloch R (2014) Two miRNA clusters reveal alternative paths in late-stage reprogramming. Cell Stem Cell 14:617-631.

Parchem RJ, Moore N, Fish JL, Parchem JG, Braga TT, Shenoy A, Oldham MC, Rubenstein JL, Schneider RA, Blelloch R (2015) miR-302 is required for timing of neural differentiation, neural tube closure, and embryonic viability. Cell Reports 12:760-773.

Krishnakumar R, Chen AF, Pantovich MG, Danial M, Parchem RJ, Labosky PA, Blelloch R (2016) FOXD3 regulates puripotent stem cell potential by simultaneously initiating and repressing enhancer activity. Cell Stem Cell 18:104-117.

Tran ND, Kissner M, Subramanyam D, Parchem RJ, Laird DJ, Blelloch RH (2016) A miR-372/let-7 axis regulates human germ versus somatic cell fates. Stem Cells 34:1985-1991.


Contact Information

 

Ronald Parchem, Ph.D.
Department of Neuroscience
Center for Cell and Gene Therapy
Baylor College of Medicine
One Baylor Plaza N1020
Houston, Texas 77030, U.S.A.

Tel: (713) 798-7872
E-mail: ronald.parchem@bcm.edu

 

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