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David J. Reiner

David J. Reiner
David J. Reiner, PhD

Associate Professor

Contact

Center for Translational Cancer Research
2121 W. Holcombe Blvd
Houston, TX 77030
dreiner@tamu.edu
Phone: 713.677.7416
Fax: 713.677.7779
Reiner Lab

Education and Training

  • Bachelor of Arts in Biology, Carleton College
  • Ph.D. in Genetics, University of Washington
  • Damon Runyon Postdoctoral Fellow, University of California, Berkeley
  • Assistant Professor, Department of Pharmacology, University of North Carolina

 

  • Co-corresponding author and designer of cover layout for January 23, 2014 issue of Molecular Cell:

Mol Cell 012314 cover

Research Interests

A long-term goal of the Reiner lab is to understand the molecular basis underlying the contribution of signal transduction to development. What determines the extraordinarily high fidelity of developmental systems – and how novel signaling mechanisms and components contribute to that fidelity – remains a fundamental gap in the field. The skeleton of most core signaling cascades has been defined by the convergence of complementary research using model genetic organisms, mechanistic analyses in mammalian cell culture, biochemical and biophysical studies, and pathophysiological definitions of important players. We even know many so-called “modulator” genes to flesh out the signaling world. Yet how these components are woven into dynamic and plastic signaling networks during development is still not well understood.

Our research bootstraps from the Ras small GTPase, the most mutated mammalian oncoprotein. Among the relatives of Ras, we look downstream of Ras (Ral), in the shadow of Ras (Rap1), and at a cousin of Ras in metabolism and development (Rheb), which also connects back to Ral. We have also found novel signals downstream of Ral, a missing link in Ras-dependent tumors. Most of our work uses the genetic model organism, C. elegans, though we have published cross-platform studies by letting the worm lead the way to insights into mammalian biology.

Another focus of the Reiner lab is to harness the power of C. elegans genetics to engineer animals for highly sensitized drug discovery screens. Here in the IBT Center for Translational Cancer Research on the 9th floor of the Alkek building is the John S. Dunn High Throughput Screening Core Facility, part of the Gulf Coast Consortia for Quantitative Biomedical Sciences. Also our neighbor on the 9th floor is the Center for Advanced Imaging, which contains state of the art confocal imaging as well as high throughput imaging instruments, and the expertise to use them. With them we are working to define a novel cross-platform drug discovery pipeline, with model organism small molecule inhibitor identification generating candidates for cell culture and mouse validation, and from there into the clinic. Consequently, our efforts are inherently collaborative. A key element of our project design is that, unlike conventional targeted drug therapy paradigms, we do not assume that we know the best target in a given system. Rather, we sensitize a system with a known mutation as an entry point for high throughput small molecule screening for specific phenotypic endpoints. We reason that the target identification can come later; we are looking for potentially valuable inhibitors in a given system regardless of the target, thereby complementing existing drug discovery paradigms. We began with oncogenic Rac and Ras as proofs of principle, and will extend to other entry points. We emphasize that in the long term our drug discovery scheme is generalizable: to other diseases with highly conserved molecular entry points (channelopathies, neurodegeneration, dystrophies, etc., as well as oncogenes) and to other model system platforms (yeast, worms, flies, frogs and fish).

Selected Publications

  1. Qi Zhang, Heather Hrach, Marco Mangone, David J Reiner (2022). Identifying the C. elegans vulval transcriptome. G3: Genes, Genomes, Genetics 12(6). PMID: 35551383.

  2. Jeff Hardin, Joel Serre, Ryan King, Elise Walck-Shannon E, David Reiner (2022) Imaging Epidermal Cell Rearrangement in the C. elegans Embryo. Methods in Molecular Biology 2438:345-376. doi: 10.1007/978-1-0716-2035-9_22. PMID: 35147953

  3. Katherine H. Pedone, Vanessa González-Pérez, Luciana E. Leopold, Neal R. Rasmussen, Channing J. Der, Adrienne D. Cox, Shawn Ahmed and David J. Reiner  (2021). Engineering threshold-based selection systems. G3: Genes, Genomes, Genetics 11(9). PMID: 34544135.

  4. Neal R. Rasmussen and David J. Reiner (2021). Nuclear translocation of the tagged endogenous MAPK MPK-1 denotes a subset of activation events in C. elegans development. J Cell Science 134(17). PMID: 34341823.

  5. Neal R. Rasmussen, Harold E. Smith and David J. Reiner (2021). The MLK-1/SCD-4 Mixed Lineage Kinase/MAP3K functions to promote dauer formation upstream of DAF-2/InsR. MicroPubl Biol doi: 10.17912/micropub.biology.000405. PMID: 34142023.

  6. Jacob I. Mardick, Neal Rasmussen, Bruce Wightman, David J. Reiner (2021). Parallel Rap1>RalGEF>Ral and Ras signals sculpt the C. elegans nervous system. Developmental Biology 477:37-48. PMID: 33991533.

  7. Neal R. Rasmussen, and David J. Reiner (2021). Ras, Ral and Rap1 in C. elegans. Methods Mol Bio 2262:423-436. PMID: 33977493.

  8. You Wu and David J. Reiner (2021). A signaling Cascade for Ral. Small GTPases 6;1-8. PMID: 33956571.

  9. Guinevere E. Ashley, Tam Duong, Max T. Levenson, Michael A.Q. Martinez, London C. Johnson, Jonathan D. Hibschman, Hanna N. Saeger, Nicholas J. Palmisano, Ryan Doonan, Raquel Martinez-Mendez, Brittany R Davidson, Wan Zhang, James Matthew Wagle, Taylor N. Medwig-Kinney, Sidney S. Sirota, Bob Goldstein, David Q. Matus, Daniel J. Dickinson, David J. Reiner, and Jordan D. Ward (2021). Genetics 217(3). PMID: 33677541.

  10. Tam Duong, Neal R. Rasmussen and David J. Reiner (2020). Insulated Switches: Dual-Function Protein RalGEFRGL-1 Promotes Developmental Fidelity (2021). Int J Mol Sci 21(20):7610. PMID: 33076222.

  11. Tam Duong, Neal R. Rasmussen, Elliot Ballato, F. Sefakor Mote and David J. Reiner (2020). The Rheb-TORC1 signaling axis functions as a developmental checkpoint. Development 147(5), PMID: 32041790.

  12. Hanna Shin, Christian Braendle, Kimberly B. Monahan, Rebecca E.W. Kaplan, Tanya P. Zand, F. Sefakor Mote, DeSean R. Craig, Eldon Peters and David J. Reiner (2019). Developmental fidelity imposed by the RGL-1 balanced switch mediating opposing signals. PLoS Genetics. 5(5):e1008056. doi: 10.1371/journal.pgen.1008056. PMID: 31086367

  13. Neal R. Rasmussen, Daniel J. Dickinson and David J. Reiner (2018)). Ras-dependent cell fate decisions are reinforced by the RAP-1 small GTPase in C. elegans. Genetics 210(4):1339-1354. PMID: 30257933

  14. Hanna Shin, Rebecca E.W. Kaplan, Tam Duong, Razan Fakieh and David J. Reiner (2018). Ral signals through a MAP4 Kinase-p38 MAP kinase cascade in C. elegans cell fate patterning. Cell Reports 24(10): 2669-2681. PMID: 30184501

  15. David J. Reiner and Erik Lundquist (2016). Small GTPases. Chapter in Wormbook. doi: 10.1895/wormbook.1.67.2 PMID: 27218782

  16. Elise Walck-Shannon, Ian Chin-Sang, David Reiner, Hunter Cochran, and Jeff Hardin (2016). CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis. PLoS Genetics 12(11): e1006415. doi: 10.1371/journal.pgen.1006415 PMID: 27861585

  17. Elise Walck-Shannon, David Reiner, and Jeff Hardin (2015). Polarized Rac-Dependent Polarized Rac-dependent protrusions drive epithelial intercalation in the embryonic epidermis of C. elegans. Development 142: 3539-3560. PMID: 26395474

  18. Ambrose R. Kidd III, Vanessa Muñiz-Medina, Channing J. Der, Adrienne D. Cox and David J. Reiner (2015). The C. elegans Chp/Wrch Ortholog CHW-1 Distinguishes LIN-18/Ryk from LIN- 17/Frizzled Signaling in Cell Polarity. PLoS ONE 10: 1-21. PMID: 26208319

  19. Martin, TD, Chen, X-W, Kaplan, REW, Saltiel, AR, Walker, CL, Reiner, DJ§,†, Der, CJ. (2014). Ral and Rheb GTPase Activating Proteins Integrate mTOR and GTPase Signaling in Aging, Autophagy, and Tumor Cell Invasion. Molecular Cell 53: 209-220. PMID: 24389102
    §co-corresponding author
    †Designed cover

  20. Dickinson, DJ, Ward, JD, Reiner DJ and Goldstein, B (2013). Engineering the C. elegans genome using Cas9-triggered homologous recombination. Nature Methods 1028-34. PMID: 23995389

  21. Peters, EC, Gossett, AJ, Goldstein, B, Der, CJ, Reiner, DJ (2013). Redundant Canonical and Non-canonical C. elegans p21-Activated Kinase Signaling Governs Cell Migrations. G3 (Bethesda) 3: 181-195. PMID: 23390595

  22. Reiner, DJ (2011) Ras Effector Switching as a Developmental Strategy. Small GTPases 2: 109-112. PMID: 21776412

  23. Zand TP, Reiner DJ§,†, Der CJ (2011). Ras Effector Switching Promotes Divergent Cell Fates in C. elegans Vulval Patterning. Developmental Cell. 20: 84-96. PMID: 21238927
    §corresponding author
    †Received two Faculty of 1000 citations

  24. Neel, NF, Martin, TD, Stratford, JK, Zand, TP, Reiner, DJ, Der, CJ (2011). The RalGEF-Ral Effector Signaling Network: the Road Less Traveled for Anti-Ras Drug Discovery. Genes and Cancer. 2: 275-287. PMID: 21779498

  25. Gonzalez-Perez, V, Reiner, DJ, Alan, JK, Mitchell, C, Edwards, LJ, Khazak, V, Der, CJ, Cox, AD. (2010) Genetic and functional characterization of putative Ras/Raf interaction inhibitors in C. elegans and mammalian cells. Journal of Molecular Signaling. 5: 2. PMID: 20178605

  26. Reiner, DJ, Gonzalez-Perez, V, Der, CJ and Cox, AD (2008). Use of C. elegans to evaluate inhibitors of Ras function in vivo. Methods in Enzymology. 439: 425-449. PMID: 18374181

  27. Reiner, DJ, Ailion, M, Thomas, JH, Meyer, BJ (2008) C. elegans anaplastic lymphoma kinase SCD-2 controls dauer formation by modulating TGF-beta signaling. Current Biology§. 18: 1101-9. PMID: 18674914
    §Full length article

  28. Reiner, DJ, Weinshenker, D, Tian, H, Thomas, JH, Nishiwaki, K, Miwa, J, Gruninger, T, Leboeuf, B, Garcia, LR (2006). Behavioral genetics of Caenorhabditis elegans unc-103-encoded erg-like K+ channel.  Journal of Neurogenetics. 20: 41-66. PMID: 16807195

  29. Petersen, CI, McFarland, TR, Stepanovic, SZ, Yang, P, Reiner, DJ, Hayashi, K, George, AL, Roden, DM, Thomas, JH, Balser, J.R.  (2004).  In vivo identification of genes that modify ether-a-go-go-related gene activity in Caenorhabditis elegans may also affect human cardiac arrhythmia.  PNAS 101(32):11773-8. PMID: 15280551

  30. Reiner, DJ, Newton, EM, Tian, H, Thomas, JH (1999).  Diverse behavioral defects caused by mutations in Caenorhabditis elegans unc-43 CaM kinase II.  Nature 402: 199-203. PMID: 10647014