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Richard S. Mann, PhD

Academic Appointments

  • Higgins Professor of Biochemistry and Molecular Biophysics
Richard S. Mann, PhD

Our lab uses the fruit fly, Drosophila melanogaster, to study three main problems: Hox protein function and specificity; appendage development; and the development and function of the adult motor system.

Our work on Hox proteins centers around two questions: 1) how these homeodomain-containing transcription factors achieve specificity in vivo and 2) what are the relevant target genes that these factors regulate to control morphogenesis? To answer these questions, we are using a variety of in vitro DNA binding assays, structural biology, in vivo reporter gene assays, and genome-wide methods to discover and validate Hox target genes and Hox binding sites. Genetic methods are used to analyze the function of putative target genes and their specific contributions to morphology.

Our work on appendage development focuses on two questions: 1) how is positional information generated along the proximo-distal (PD) axis and 2) how is cell proliferation regulated and coordinated with cell differentiation? To answer the first question, our main approach is to dissect at high resolution the transcriptional responses of genes expressed at specific positions along the PD axis, primarily in the legs. To answer the second question, we are identifying the genes and pathways that selector genes regulate to modulate cell proliferation during appendage development.

Our work on the adult motor system stems from our work on leg development. Here, we are studying how the motor neurons that innervate the adult leg are generated and specified to target the correct muscles and generate the correct dendritic pattern in the CNS. Using this information, we are beginning to study how the movement of the legs is coordinated by local interneurons and sensory feedback. Locomotion assays to study adult walking behavior are used to analyze the wild type circuitry and the consequences to when this circuit is perturbed.

Control of pattern formation by homeotic genes and their downstream targets in Drosophila.

Departmental Appointments

  • Department of Biochemistry and Molecular Biophysics

Lab Locations

  • Jerome L. Greene Science Center

    3227 Broadway
    L9-001
    New York, NY 10027
    Phone:
    (212) 853-1028
    Email:
    rsm10@cumc.columbia.edu

Research Interests

  • Stem Cell Biology
  • Neurogenetics
  • Axon Pathfinding and Synaptogenesis
  • Cell Specification and Differentiation
  • Cellular/Molecular/Developmental Neuroscience

NIH Grants

  • INTERPRETING AND DEPLOYING GENOMIC INFORMATION DURING ANIMAL DEVELOPMENT (Federal Gov)

    May 3 2016 - Apr 30 2021

    PROXIMO-DISTAL PATTERNING IN THE DROSOPHILA APPENDAGES (Federal Gov)

    Jan 1 2015 - Nov 30 2018

    FUNCTIONAL MAPPING OF PATHWAYS FOR SENSORY-MOTOR INTEGRATION (Federal Gov)

    Sep 30 2014 - Jul 31 2017

    FINDING COMPONENTS OF DROSOPHILA MOTOR CIRCUITRY REQUIRED FOR COORDINATED WALKING (Federal Gov)

    Jul 1 2014 - Jun 30 2017

    MOLECULAR GENETICS OF SEGMENT IDENTITY (Federal Gov)

    Aug 1 1992 - Mar 31 2017

    AG-SS-2945-12 THE DECLINE OF MOTOR COORDINATING DURING AGING (Private)

    Oct 1 2012 - Sep 30 2016

    NATIONAL CENTER: MULTISCALE ANALYSIS OF GENOMIC AND CELLULAR NETWORKS (MAGNET) (Federal Gov)

    Sep 26 2005 - Jul 31 2016

    GENETIC DISSECTION OF LOCOMOTION (Federal Gov)

    Jun 1 2014 - May 31 2016

    CHARACTERIZATION OF HOX TRANSCRIPTION FACTOR COMPLEXES USING PROTEOMICS (Federal Gov)

    Sep 1 2011 - Aug 31 2014

    CONNECTING A TUMOR SUPPRESSOR PATHWAY WITH THE PROTO-ONCOGENES MEIS AND PBX (Private)

    Jul 1 2011 - Jun 30 2014

    INDENTIFICATION OF HOX TARGET GENES CONTROLLING TISSUE GROWT H (Federal Gov)

    Jan 1 2009 - Sep 30 2010

    THE ROLE OF HOX GENES IN DROSOPHILA MOTOR NEURON DEVELOPMENT AND FUNCTION (Private)

    Apr 1 2006 - Mar 31 2010

    DISSECTING A COMBINED SIGNAL GRADIENT RESPONSE ELEMENT (Federal Gov)

    May 1 2006 - Apr 30 2009

Publications

  • Mendes CS, Bartos I, Márka Z, Akay T, Márka S, Mann RS. Quantification of gait parameters in freely walking rodents. BMC Biol. (2015) Jul 22;13:50. doi:10.1186/s12915-015-0154-0. PMID: 26197889.
  • Enriquez J, Venkatasubramanian L, Baek M, Peterson M, Aghayeva U, Mann RS. Specification of individual adult motor neuron morphologies by combinatorial transcription factor codes. Neuron. (2015) May 20;86(4):955-70. doi:10.1016/j.neuron.2015.04.011. Epub 2015 May 7. PMID: 25959734; PMCID: PMC4441546.
  • Abe N, Dror I, Yang L, Slattery M, Zhou T, Bussemaker HJ, Rohs R, Mann RS. Deconvolving the recognition of DNA shape from sequence. Cell. (2015) Apr 9;161(2):307-18. doi: 10.1016/j.cell.2015.02.008. Epub 2015 Apr 2. PMID: 25843630; PMCID: PMC4422406.
  • Bouchard MB, Voleti V, Mendes CS, Lacefield C, Grueber WB, Mann RS, Bruno RM, Hillman EM. Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms. Nat Photonics. (2015) Feb;9(2):113-119. PMID: 25663846; PMCID: PMC4317333.
  • Crocker J, Abe N, Rinaldi L, McGregor AP, Frankel N, Wang S, Alsawadi A, Valenti P, Plaza S, Payre F, Mann RS, Stern DL. Low affinity binding site clusters confer hox specificity and regulatory robustness. Cell. (2015) Jan 15;160(1-2):191-203. doi: 10.1016/j.cell.2014.11.041. Epub 2014 Dec 31. PMID: 25557079; PMCID: PMC4449256.
  • Mendes CS, Rajendren SV, Bartos I, Márka S, Mann RS. Kinematic responses to changes in walking orientation and gravitational load in Drosophila melanogaster. PLoS One. (2014) Oct 28;9(10):e109204. doi: 10.1371/journal.pone.0109204. eCollection 2014. PMID: 25350743;  PMCID: PMC4211655.
  • Agelopoulos M, McKay DJ, Mann RS. cgChIP: a cell type- and gene-specific method for chromatin analysis. Methods Mol Biol. (2014);1196:291-306. doi:10.1007/978-1-4939-1242-1_18. PubMed PMID: 25151171; PMCID: PMC4439094.
  • Slattery M, Voutev R, Ma L, Nègre N, White KP, Mann RS. Divergent transcriptional regulatory logic at the intersection of tissue growth and developmental patterning. PLoS Genet. (2013) 9(9):e1003753. doi:10.1371/journal.pgen.1003753. Epub 2013 Sep 5. PMID: 24039600; PMCID: PMC3764184.
  • Mann RS. Neuroscience. The Michael Jackson fly. Science. (2014) Apr 4;344(6179):48-9. doi: 10.1126/science.1252431. PMID: 24700848; PMCID: PMC4143233.
  • Baek M, Enriquez J, Mann RS. Dual role for Hox genes and Hox co-factors in conferring leg motoneuron survival and identity in Drosophila. Development. (2013) May;140(9):2027-38. doi: 10.1242/dev.090902. Epub 2013 Mar 27. PMID: 23536569; PMCID: PMC3631975.