David Breslow, PhD
Assistant Professor, Molecular, Cellular and Developmental Biology
Research & Publications
Biography
Locations
Research Summary
The goal of David Breslow's current research is understanding the functions of the mammalian primary cilium, a micron-scale structure protruding from the surface of most cells in the human body. Overlooked for many years, the cilium has recently been found to control key aspects of cellular and organismal physiology and to be disrupted in a group of pediatric diseases known as ciliopathies. Using a combination of functional screening, microscopy and biochemistry, the Breslow lab is investigating the basic processes by which cilia are assembled, maintained, and disassembled. Areas of particular interest include understanding how the cilium serves as an essential organizing center for select signaling pathways (e.g. Hedgehog signal transduction) and dissecting the complex interplay between cell cycle progression and regulation of of cilium assembly/disassembly. Together these studies aim to provide fundamental biological insights, to shed light on the pathogenic mechanisms of ciliopathies, and to reveal new strategies for targeting Hedgehog-driven cancers.
Coauthors
Research Interests
Organelle Biogenesis; Cell Compartmentation; Cell Cycle; Cell Division; Cell Biology; Homeostasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Malformations; Signal Transduction; Genomics; Cell Shape; Organelle Shape; High-Throughput Screening Assays
Selected Publications
- Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndromeBruel A, Ganga A, Nosková L, Valenzuela I, Martinovic J, Duffourd Y, Zikánová M, Majer F, Kmoch S, Mohler M, Sun J, Sweeney L, Martínez-Gil N, Thauvin-Robinet C, Breslow D. Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome. Human Molecular Genetics 2023, 32: 2822-2831. PMID: 37384395, PMCID: PMC10481091, DOI: 10.1093/hmg/ddad109.
- Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathwayGanga AK, Kennedy MC, Oguchi ME, Gray S, Oliver KE, Knight TA, De La Cruz EM, Homma Y, Fukuda M, Breslow DK. Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway. Current Biology 2021, 31: 2895-2905.e7. PMID: 33989527, PMCID: PMC8282722, DOI: 10.1016/j.cub.2021.04.075.
- Mechanism and Regulation of Centriole and Cilium BiogenesisBreslow DK, Holland AJ. Mechanism and Regulation of Centriole and Cilium Biogenesis. Annual Review Of Biochemistry 2019, 88: 1-34. PMID: 30601682, PMCID: PMC6588485, DOI: 10.1146/annurev-biochem-013118-111153.
- A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathiesBreslow DK, Hoogendoorn S, Kopp AR, Morgens DW, Vu BK, Kennedy MC, Han K, Li A, Hess GT, Bassik MC, Chen JK, Nachury MV. A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies. Nature Genetics 2018, 50: 460-471. PMID: 29459677, PMCID: PMC5862771, DOI: 10.1038/s41588-018-0054-7.
- An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrierBreslow DK, Koslover EF, Seydel F, Spakowitz AJ, Nachury MV. An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier. Journal Of Cell Biology 2013, 203: 129-147. PMID: 24100294, PMCID: PMC3798247, DOI: 10.1083/jcb.201212024.
- Orm family proteins mediate sphingolipid homeostasisBreslow DK, Collins SR, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, Ejsing CS, Weissman JS. Orm family proteins mediate sphingolipid homeostasis. Nature 2010, 463: 1048-1053. PMID: 20182505, PMCID: PMC2877384, DOI: 10.1038/nature08787.
- Chapter 11 Analysis of soluble protein entry into primary cilia using semipermeabilized cellsBreslow DK, Nachury MV. Chapter 11 Analysis of soluble protein entry into primary cilia using semipermeabilized cells. 2015, 127: 203-221. PMID: 25837393, PMCID: PMC4797650, DOI: 10.1016/bs.mcb.2014.12.006.
- The Intraflagellar Transport Protein IFT27 Promotes BBSome Exit from Cilia through the GTPase ARL6/BBS3Liew GM, Ye F, Nager AR, Murphy JP, Lee JS, Aguiar M, Breslow DK, Gygi SP, Nachury MV. The Intraflagellar Transport Protein IFT27 Promotes BBSome Exit from Cilia through the GTPase ARL6/BBS3. Developmental Cell 2014, 31: 265-278. PMID: 25443296, PMCID: PMC4255629, DOI: 10.1016/j.devcel.2014.09.004.
- Sphingolipid Homeostasis in the Endoplasmic Reticulum and BeyondBreslow DK. Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond. Cold Spring Harbor Perspectives In Biology 2013, 5: a013326. PMID: 23545423, PMCID: PMC3683901, DOI: 10.1101/cshperspect.a013326.
- Single molecule imaging reveals a major role for diffusion in the exploration of ciliary space by signaling receptorsYe F, Breslow DK, Koslover EF, Spakowitz AJ, Nelson WJ, Nachury MV. Single molecule imaging reveals a major role for diffusion in the exploration of ciliary space by signaling receptors. ELife 2013, 2: e00654. PMID: 23930224, PMCID: PMC3736543, DOI: 10.7554/elife.00654.
- Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiaeRoelants FM, Breslow DK, Muir A, Weissman JS, Thorner J. Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 19222-19227. PMID: 22080611, PMCID: PMC3228448, DOI: 10.1073/pnas.1116948108.
- A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and SmoothenedSeo S, Zhang Q, Bugge K, Breslow DK, Searby CC, Nachury MV, Sheffield VC. A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened. PLOS Genetics 2011, 7: e1002358. PMID: 22072986, PMCID: PMC3207910, DOI: 10.1371/journal.pgen.1002358.
- Primary Cilia: How to Keep the Riff-Raff in the Plasma MembraneBreslow DK, Nachury MV. Primary Cilia: How to Keep the Riff-Raff in the Plasma Membrane. Current Biology 2011, 21: r434-r436. PMID: 21640903, DOI: 10.1016/j.cub.2011.04.039.
- Membranes in Balance: Mechanisms of Sphingolipid HomeostasisBreslow DK, Weissman JS. Membranes in Balance: Mechanisms of Sphingolipid Homeostasis. Molecular Cell 2010, 40: 267-279. PMID: 20965421, PMCID: PMC2987644, DOI: 10.1016/j.molcel.2010.10.005.
- A comprehensive strategy enabling high-resolution functional analysis of the yeast genomeBreslow DK, Cameron DM, Collins SR, Schuldiner M, Stewart-Ornstein J, Newman HW, Braun S, Madhani HD, Krogan NJ, Weissman JS. A comprehensive strategy enabling high-resolution functional analysis of the yeast genome. Nature Methods 2008, 5: 711-718. PMID: 18622397, PMCID: PMC2756093, DOI: 10.1038/nmeth.1234.
- Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noiseNewman JR, Ghaemmaghami S, Ihmels J, Breslow DK, Noble M, DeRisi JL, Weissman JS. Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature 2006, 441: 840-846. PMID: 16699522, DOI: 10.1038/nature04785.