Assistant Professor of Oncological Sciences and
Adjunct Assistant Professor of Bioengineering and of Biochemistry
A.B. Harvard University
Ph.D. University of California, San Francisco
Ben Myers' Lab Page
Ben Myers' PubMed Literature Search
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Molecular Biology Program
Biological Chemistry Program
Signaling across the membrane in development and cancer: Hedgehog, Wnt,
primary cilium, membrane proteins / lipids, second messengers
In multicellular organisms, cells need to communicate with one another to ensure proper tissue and organ development, and to prevent diseases such as cancer. My lab studies a key aspect of this process: how extracellular signals are transmitted across the membrane to the cell interior. We are tackling this problem from an interdisciplinary perspective, drawing on protein and lipid biochemistry, cell biology, physiology, embryology, and a range of related approaches.
Current research in my lab focuses on:
- Biochemical mechanisms of signal transduction in the Hedgehog pathway, a quintessential cell fate specification cascade that controls the development of nearly all of our tissues and organs. Besides its relevance to development and cancer, our work on Hedgehog has led us to discover new principles in cellular signaling regarding a) how lipids can bind to and activate membrane receptors, and b) how membrane receptors can control intracellular kinases.
- The physiology of the primary cilium, a tiny antenna-shaped membrane protrusion critical to Hedgehog signaling as well as a range of related pathways in the nervous, cardiovascular, and musculoskeletal systems
- Developing new tools to study how transmembrane signaling affects cellular identity more broadly throughout animal biology
A better understanding of these processes will teach us how cellular identity is specified during development and in post-embryonic tissues. It will also help us to design better therapies for birth defects, cancers, and other diseases.
- , J, , D, , J, , J, , D, , , J, , S, , I, , M, , N, , D,, R, Myers, B. Smoothened Transduces Hedgehog Signals via Activity-Dependent Sequestration of PKA Catalytic Subunits. biorxiv, July 2 2019. https://www.biorxiv.org/content/10.1101/2020.07.01.183079v1
- Deshpande, I, Liang, J, Hedeen, D, Roberts, K.J., Zhang, Y, Ha, B, Latorraca, N.R., Faust, B, Dror, R.O., Beachy, P.A., Myers, B.R.^, Manglik, A.^ Smoothened Stimulation by Membrane Sterols Drives Hedgehog Pathway Activation. Nature, 2019 Jul 1; https://doi.org/10.1038/s41586-019-1355-4 (^ = corresponding author)
- Zhang, Y, Bulkley, DP, Xin, Y, Roberts, KJ, Asarnow, DE, Sharma, A, Myers, B.R., Cho W, Cheng Y, Beachy PA. Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched. Cell, Nov 15;175(5):1352-1364.e14 (2018)
- Myers, B. R.*^, Neahring, L.*, Zhang, Y., Roberts, K. R., Beachy, P. A.^. Rapid, direct activity assays for Smoothened reveal
Hedgehog pathway regulation by membrane cholesterol and extracellular sodium. Proc Nat Acad Sci10.1073/pnas.1717891115 (2017) (* = first author; ^ = corresponding author). pdf
- Commentary by Blassberg and Briscoe in Dev Cell: pdf
- Sweeney, R.T.*, McClary, A.C.*, Myers, B.R.*, Biscocho, J.*, et al. Identification of Recurrent SMO and BRAF Mutations in Ameloblastomas. Nat Gen46(7):722-5 (2014). (* = first author)
- Myers, B. R., Sever, N., Chong, Y. C., Kim, J., Belani, J. D., Rychnovsky, S., Bazan, J. F., Beachy, P. A. Hedgehog Pathway Modulation by Multiple Lipid Binding Sites on the Smoothened Effector of Signal Response. Dev Cell 26(4):346-57 (2013).
- Myers, B. R., Sigal, Y. M., Julius, D. Evolution of Thermal Response Properties in a Cold-Activated TRP Channel. PLoS ONE 4(5): e5741. doi:10.1371/journal.pone.0005741 (2009).
- Prober, D. A., Zimmerman, S., Myers, B. R., McDermott, B. M., Caron, S., Rihel, J., Kim, S., Kettleborough, R. N. W., Stemple, D. L., Solnica-Krezel, L., Julius, D., Hudspeth, A. J., Schier, A. F. Zebrafish TRPA1 Channels are Required for Behavioral Responses to Mustard Oil but not for Thermosensation or Mechanosensory Hair Cell Function. J Neurosci 28(40):10102-10 (2008).
- Myers, B. R., Saimi, Y., Kung, C., Julius, D. Multiple Unbiased Prospective Screens Identify TRP Channels and their Conserved Gating Elements. J Gen Physiol. 132(5): 481-6 (2008).
- Myers, B. R., Bohlen, C., Julius, D. A Yeast Genetic Screen Reveals a Critical Role for the Pore Helix Domain in TRP Channel Gating. Neuron 58(3):362-73 (2008).
- Myers, B. R., Julius. D. TRP Channel Structural Biology: New Roles for an Old Fold. Neuron 54(6):847-50 (2007).
- Desai, B. N., Myers, B. R., Schreiber, S. L. FKBP12-rapamycin associated protein associates with mitochondria and senses osmotic stress via an intermediate mitochondrial dysfunction. Proc. Natl. Acad. Sci. USA 99(7):4319-24 (2002).