Ruben’s research focuses on how neurons communicate and how dysfunction at the molecular level contributes to disruption of this communication in neurological disorders. Ruben is a PhD candidate in the Shen Lab. His current work includes investigation of synaptic vesicle regulation and synaptic specificity. Neurons largely communicate via chemical synapses. At the pre-synaptic neuron terminal, neurotransmitters are packaged in synaptic vesicles and released into the synapse to convey messages to post-synaptic neurons. The molecular mechanisms that regulate synaptic vesicle activity are crucial for the appropriate function of neural networks. Disruptions of these processes appear to be involved in a variety of neurological disorders. Ruben is investigating the molecular mechanisms involved in these processes to better understand how neurons communicate and how molecular dysfunction might disrupt this communication. In his free time, Ruben is involved in several efforts to promote student and community mental health and well-being at Stanford and beyond. He also likes to run, hike and play ultimate frisbee.
The orphan nuclear receptor NR4A1 specifies a distinct subpopulation of quiescent myeloid-biased long-term HSCs.
Stem cells (Dayton, Ohio)
2015; 33 (1): 278–88
Hematopoiesis is maintained throughout life by self-renewing hematopoietic stem cells (HSCs) that differentiate to produce both myeloid and lymphoid cells. The NR4A family of orphan nuclear receptors, which regulates cell fate in many tissues, appears to play a key role in HSC proliferation and differentiation. Using a NR4A1(GFP) BAC transgenic reporter mouse we have investigated NR4A1 expression and its regulation in early hematopoiesis. We show that NR4A1 is most highly expressed in a subset of Lin(-) Sca-1(+) c-Kit(+) CD48(-) CD150(+) long-term (LT) HSCs, and its expression is tightly associated with HSC quiescence. We also show that NR4A1 expression in HSCs is induced by PGE2, a known enhancer of stem cell engraftment potential. Finally, we find that both NR4A1(GFP+) and NR4A1(GFP-) HSCs successfully engraft primary and secondary irradiated hosts; however, NR4A1(GFP+) HSCs are distinctly myeloid-biased. These results show that NR4A1 expression identifies a highly quiescent and distinct population of myeloid-biased LT-HSCs.
View details for DOI 10.1002/stem.1852
View details for PubMedID 25284014
View details for PubMedCentralID PMC4270858