Who is Clarence?

Clarence obtained his MSc and DPhil from the University of Oxford, England in the labs of Professor Udo Oppermann and Professor Alison Noble. He studied Biomedical Engineering and prior to that, Mechatronics Engineering. Now, Clarence is the Platform Manager for Microscopy and Image Analysis at the Laboratory of Systems Pharmacology (LSP) under Professor Peter Sorger, as well as a research associate at the Image and Data Analysis Core (IDAC) under Dr. Hunter Elliott, and regularly works with the Nikon Imaging Center (NIC) under Dr. Jennifer Waters at Harvard Medical School (HMS). 
  • Still good...

    A cell optoporated with propidium iodide (a DNA intercalator, shown in red) still managers to divide

  • irf5 colon
  • actin and osteoclast

    Osteoclasts...

    ...are the cells that clear away bone and have a characteristic actin ring and multiple nuclei (sometimes as many as 30!)

  • BRD4

    It's a pile of FRAP!

    Fluorescence Recovery After Photobleaching (FRAP) can reveal how well a protein is bound to its target in presence of a drug

  • collagen

    Comparing extracellular matrix in disease and healthy tissue

    Collagen and elastin produce a unique second harmonic signal and two photon excitation fluorescence respectively

  • cell 7

    Dead or alive

    A temporary hole can be made in the cell membrane to allow proteins that normally would not enter a living cell

  • cd68
  • cd68 crop

Publications

SB Hatch*, C Yapp*, RC Montenegro et al., 2017, Assessing histone demethylase inhibitors in cells: lessons learned, Epigenetics and Chromatin (preprint)

A Kawamura, M Munzel, T Kojima, C Yapp et al., 2017, Highly Selective inhibition of histone demethylases by de novo macrocyclic peptides, Nature Communications (preprint)

C Yapp, U Oppermann, A Price et al., 2016, H3K27me3 demethylases regulate in vitro chondrogenesis and chondrocyte activity in osteoarthritis, Arthritis Res. Ther., 18(1):158

C Yapp, C Rogers, Pavel Savitsky et al., 2016, Frapid: achieving full automation of FRAP for chemical probe validation, Biomed. Opt. Express, 7(2):422-441

MK Kuzniarska, C Yapp, PA Hulley, 2016, Using fluorescence recovery after photobleaching to study gap junctional communication in vitro, Gap Junction Protocols, 1437:171-179

SG Dakin, FM Estrada, C Yapp et al., 2016, Inflammation activation and resolution in human tendon disease, Sci. Transl. Med., 7(311):173 

CL Sutherell, C Tallant, O Monteiro, C Yapp et al., 2016, Identificaton and development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex,  J. Med. Chem.

TM Grant, C Yapp et al., 2015, The Mechanical, structural, and compositional changes of tendon exposed to elastase, Ann. Biomed. Eng.

CC Thinnes, A Tumber, C Yapp et al., 2015, Betti Reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases, Chem. Commun.

M Philpott, CM Rogers, C Yapp, et al., 2014, Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching, Epigenetics & Chromatin

MK Kuzniarska, C Yapp et al., 2014, Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching. J. Biomed. Opt.

RJ Hopkinson*, A Tumber*, C Yapp* et al., 2013, 5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation. Chemical Science

I Adekanmbi, NZ Baboldashti, C Yapp et al. 2013, A novel in vitro loading system for high frequency loading of cultured tendon fascicles. Med Eng Phys. 

U Tirlapur & C Yapp, 2011, Near Infrared Three-Dimensional Nonlinear Optical Monitoring of Stem Cell Differentiation. Optical  Fluorescence Microscopy

C Yapp & ASK Bin, 2008, Teaching Image Processing: A Two Step Process. Computer Applications in Engineering Education. 16(3):211-222

LB Leong & C Yapp, 2008, Dissipative Relativistic Standard Map. Chaos, Solitons & Fractals. 37(5): 1300-1304

 

 

Research Interests

During his DPhil study, he developed optoporation, a near-infrared laser microscopy technique to introduce biological macromolecules into living cells. He spent four years as a postdoctoral scientist at the Structural Genomics Consortium and Target Discovery Institute (Oxford, UK), where his project took his fascination in applying optical methods for understanding and manipulating biology to develop image-based high-content phenotypical cell-based assays. To identify potent small molecule inhibitors against novel epigenetic targets, he designed a Fluorescence Recovery After Photobleaching (FRAP) assay and a histone mark immunofluorescence assay, which are now routinely used to validate chemical probes against bromodomains (ATAD2, BRD4, BRPF1B, BRD9, CECR2, CREBBP, and SMARCA) and demethylases (JARID1B, JMJD1, JMJD2A, JMJD3, and FBXL11) respectively. His assays have led to the declaration of over 20 chemical probes that are now freely distributed through the SGC and are being used to probe the biological functions of these new targets. In May 2013, Clarence wrote and was awarded a grant to further develop and automate the FRAP assay, which led to a 4-fold increase in data throughput. During his time as a postdoctoral scientist, he also served as the microscopy facility manager at the Botnar Research Centre and Target Discovery Institute where he provided collaborative experimental design on 16 wide ranging projects that utilized timelapse, single and multiphoton, and high content microscopy towards the fields of stem cell differentiation, inflammation, DNA damage, and 3D scaffolds for tissue engineering and regeneration.

At the LSP and IDAC, Clarence aims to apply his interests in new microscopy techniques and unsupervised machine learning image analysis algorithms to solve problems.