Neural Development & Stem Cell Biology
We are interested in asymmetric cell division, retinal stem cells, pancreatic stem cells, as well as cell lineage and brain development. Our lab is interested in the lineage steps in the development of the mammalian brain from totipotent embryonic stem (blastocyst) cells to neural stem cells to more restricted neural progenitor cells that make neurons and glia. Our lab discovered adult mouse and human pancreatic stem cells, whose progeny have the ability to produce new endocrine insulin producing cells that may be useful in treating diabetes in the future. Our lab was the first to report retinal stem cells in the adult mouse and human eye. This work has resulted in the ability to grow retinal stem cells in large numbers in the lab and differentiate them into all the different cell types in the retina. More remarkable we found a way to activate retinal stem cells resident in the eye.
- Sachewsky et al. Primitive neural stem cells in the adult mammalian brain give rise to GFAP-expressing definitive neural stem cells. Stem Cell Reports. 2(6) (2014) 810-824.
- Smukler et al. The adult mouse and human pancreas contain multipotential stem cells that express insulin. Cell Stem Cell. 8 (2011) 281-293.
- Tropepe et al. Retinal stem cells in the adult mammalian eye. Science. 287 (2000) 2032-2036.
Neurobiology of Motivation
The primary objective for our Neurobiology of Motivation research is to characterize the neurobiological substrates of motivation. Our overall hypothesis is that separate, double dissociable, neural mechanisms underlie the rewarding effects of opiates in drug naive versus drug-dependent and deprived animals.
- Vargas-Perez et al. Ventral tegmental area BDNF induces an opiate-dependent-like reward state in naive rats. Science. 324 (2009) 1732-1734.
- Grieder et al. Identification of CRF neurons in the ventral tegmentatal area that control the aversive effects of nicotine withdrawal. Nature Neuroscience. 17(12) (2014) 1751-1758.
Learning and Memory
A mutational analysis has begun to reveal the component processes of Learning and Memory, our third area of research. We have developed associative (classical conditioning) and non-associative (habituation) learning paradigms using olfactory and taste stimuli in the best-understood multicultural organism, the worm C. elegans. Mutational screens in progress have identified new genes, which code for critical components of associative learning (lrn-1 and lrn-2). These new genes reveal the separable neuronal and molecular substrates underlying associative learning and habituation. Mutations in an insulin gene (ins-1) block selectively memory retrieval but not memory acquisition.
- Lin et al. Insulin signaling plays a dual role in Caenorhabditis elegans memory acquisition and memory retrieval. Journal of Neuroscience. 30 (2010) 8001-8011.
- Pereira, et al. Two forms of learning following training to a single odorant in Caenorhabditis elegans AWC neurons. Journal of Neuroscience. 32 (2012) 9035-9044.